Trial Outcomes & Findings for Study of Harmine in Healthy Subjects (NCT NCT05526430)
NCT ID: NCT05526430
Last Updated: 2025-01-16
Results Overview
DLT which is defined if have any one of the following: Patient Rated Inventory of Side Effects (PRISE): 0-51, higher scores indicate more adverse events observed Brief Psychiatric Rating Scale (BPRS): 4 - 28, higher scores indicate more symptoms of psychosis Vitals: blood pressure and heart rate will all be measured - anything outside of the following ranges will be noted: * Symptomatic hypotension, or \> 20% decrease in systolic blood pressure (SBP) from pre-dosing and an absolute SBP \< 90; or * Symptomatic hypertension, or \> 20% increase in SBP or diastolic blood pressure (DBP) from predosing and absolute SBP \> 170 or DBP \> 95; * New onset tachycardia (heart rate \>100 bpm) and \>20% increase from pre-dosing; or symptomatic bradycardia (heart rate \<60 bpm) and \> 20% decrease from pre-dosing. * Signs and symptoms of cardiac ischemia, defined by acute ischemic changes on ECG with or without concomitant symptoms
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
27 participants
Primary outcome timeframe
24 hours
Results posted on
2025-01-16
Participant Flow
Between September 2022, and June 2023, a total of 34 participants signed consent with 7 failed screening. 27 were enrolled
Participant milestones
| Measure |
Harmine Hydrochloride 100mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
12
|
4
|
1
|
|
Overall Study
COMPLETED
|
10
|
10
|
4
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
0
|
0
|
Reasons for withdrawal
| Measure |
Harmine Hydrochloride 100mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
0
|
0
|
Baseline Characteristics
Study of Harmine in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Harmine Dose 100 mg
n=10 Participants
Each study subject received a single oral dose of harmine in this single ascending dose design.
Harmine Hydrochloride Capsules: capsules taken orally
|
Harmine 200 mg
n=10 Participants
Each study subject received a single oral dose of harmine in this single ascending dose design.
Harmine Hydrochloride Capsules: capsules taken orally
|
Harmine >200mg
n=5 Participants
Each study subject received a single oral dose of harmine in this single ascending dose design.
Harmine Hydrochloride Capsules: capsules taken orally
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
28.9 years
STANDARD_DEVIATION 6.6 • n=99 Participants
|
31.1 years
STANDARD_DEVIATION 7.3 • n=107 Participants
|
29.4 years
STANDARD_DEVIATION 3.9 • n=206 Participants
|
29.9 years
STANDARD_DEVIATION 6.3 • n=7 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
13 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
6 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
18 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Weight
|
66.2 kg
STANDARD_DEVIATION 10.8 • n=99 Participants
|
69.7 kg
STANDARD_DEVIATION 14.9 • n=107 Participants
|
76 kg
STANDARD_DEVIATION 22.6 • n=206 Participants
|
69.6 kg
STANDARD_DEVIATION 15 • n=7 Participants
|
|
Body mass index
|
24.8 kg/m^2
STANDARD_DEVIATION 2.7 • n=99 Participants
|
24.5 kg/m^2
STANDARD_DEVIATION 3.0 • n=107 Participants
|
25.2 kg/m^2
STANDARD_DEVIATION 4.0 • n=206 Participants
|
24.8 kg/m^2
STANDARD_DEVIATION 3.0 • n=7 Participants
|
|
Education level
Some college
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Education level
Graduated 2-year college/trade school
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Education level
Graduated 4-year college
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
|
Education level
Some graduate/professional school
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
10 Participants
n=7 Participants
|
|
Education level
Completed graduate/professional school
|
4 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
|
Marital status
Married/living with someone as if married
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
|
Marital status
Never married
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
16 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: 24 hoursDLT which is defined if have any one of the following: Patient Rated Inventory of Side Effects (PRISE): 0-51, higher scores indicate more adverse events observed Brief Psychiatric Rating Scale (BPRS): 4 - 28, higher scores indicate more symptoms of psychosis Vitals: blood pressure and heart rate will all be measured - anything outside of the following ranges will be noted: * Symptomatic hypotension, or \> 20% decrease in systolic blood pressure (SBP) from pre-dosing and an absolute SBP \< 90; or * Symptomatic hypertension, or \> 20% increase in SBP or diastolic blood pressure (DBP) from predosing and absolute SBP \> 170 or DBP \> 95; * New onset tachycardia (heart rate \>100 bpm) and \>20% increase from pre-dosing; or symptomatic bradycardia (heart rate \<60 bpm) and \> 20% decrease from pre-dosing. * Signs and symptoms of cardiac ischemia, defined by acute ischemic changes on ECG with or without concomitant symptoms
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=4 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
n=1 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Number of Participants With Dose Limiting Toxicity (DLT)
|
0 Participants
|
6 Participants
|
4 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: 24 hoursThe MTD was determined to be between 100 and 200mg and is weight-based.
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=25 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD) of Oral Harmine HCl Based on Dose Limiting Toxicity (DLT)
|
2.7 mg/kg
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hoursPopulation: 300mg and 500mg arm combined
Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Visual Analog Scale (VAS) - Nausea
baseline
|
0.13 score on a scale
Interval 0.0 to 10.0
|
0.33 score on a scale
Interval 0.0 to 10.0
|
0.10 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
0.5 hours
|
0.71 score on a scale
Interval 0.0 to 10.0
|
0.80 score on a scale
Interval 0.0 to 10.0
|
0.12 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
1.5 hours
|
0.44 score on a scale
Interval 0.0 to 10.0
|
2.25 score on a scale
Interval 0.0 to 10.0
|
2.82 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
2 hours
|
0.69 score on a scale
Interval 0.0 to 10.0
|
1.78 score on a scale
Interval 0.0 to 10.0
|
2.22 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
3 hours
|
0.25 score on a scale
Interval 0.0 to 10.0
|
0.93 score on a scale
Interval 0.0 to 10.0
|
1.04 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
24 hours
|
0.25 score on a scale
Interval 0.0 to 10.0
|
0.32 score on a scale
Interval 0.0 to 10.0
|
0.08 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
1 hour
|
0.39 score on a scale
Interval 0.0 to 10.0
|
2.40 score on a scale
Interval 0.0 to 10.0
|
2.30 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
4 hours
|
0.37 score on a scale
Interval 0.0 to 10.0
|
0.48 score on a scale
Interval 0.0 to 10.0
|
0.94 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
5 hours
|
0.23 score on a scale
Interval 0.0 to 10.0
|
0.46 score on a scale
Interval 0.0 to 10.0
|
0.60 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
6 hours
|
0.24 score on a scale
Interval 0.0 to 10.0
|
0.29 score on a scale
Interval 0.0 to 10.0
|
0.16 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
7 hours
|
0.28 score on a scale
Interval 0.0 to 10.0
|
0.65 score on a scale
Interval 0.0 to 10.0
|
0.14 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Nausea
8 hours
|
0.23 score on a scale
Interval 0.0 to 10.0
|
0.39 score on a scale
Interval 0.0 to 10.0
|
0.16 score on a scale
Interval 0.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hoursPopulation: 300mg and 500mg arm combined
Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Visual Analog Scale (VAS) - Hunger
baseline
|
2.31 score on a scale
Interval 0.0 to 10.0
|
3.91 score on a scale
Interval 0.0 to 10.0
|
2.96 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
0.5 hours
|
4.10 score on a scale
Interval 0.0 to 10.0
|
3.40 score on a scale
Interval 0.0 to 10.0
|
4.32 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
1 hour
|
2.64 score on a scale
Interval 0.0 to 10.0
|
3.58 score on a scale
Interval 0.0 to 10.0
|
4.66 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
3 hours
|
4.68 score on a scale
Interval 0.0 to 10.0
|
4.65 score on a scale
Interval 0.0 to 10.0
|
5.36 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
4 hours
|
4.14 score on a scale
Interval 0.0 to 10.0
|
4.78 score on a scale
Interval 0.0 to 10.0
|
6.16 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
7 hours
|
3.66 score on a scale
Interval 0.0 to 10.0
|
3.35 score on a scale
Interval 0.0 to 10.0
|
4.02 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
8 hours
|
2.87 score on a scale
Interval 0.0 to 10.0
|
4.29 score on a scale
Interval 0.0 to 10.0
|
4.30 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
1.5 hours
|
5.39 score on a scale
Interval 0.0 to 10.0
|
4.26 score on a scale
Interval 0.0 to 10.0
|
5.88 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
2 hours
|
5.38 score on a scale
Interval 0.0 to 10.0
|
4.74 score on a scale
Interval 0.0 to 10.0
|
4.94 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
5 hours
|
2.56 score on a scale
Interval 0.0 to 10.0
|
1.85 score on a scale
Interval 0.0 to 10.0
|
2.54 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
6 hours
|
2.98 score on a scale
Interval 0.0 to 10.0
|
2.02 score on a scale
Interval 0.0 to 10.0
|
3.86 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Hunger
24 hours
|
3.95 score on a scale
Interval 0.0 to 10.0
|
3.51 score on a scale
Interval 0.0 to 10.0
|
4.74 score on a scale
Interval 0.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hoursPopulation: 300mg and 500mg arm combined
Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
baseline
|
0.80 score on a scale
Interval 0.0 to 10.0
|
0.44 score on a scale
Interval 0.0 to 10.0
|
0.12 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
0.5 hours
|
0.77 score on a scale
Interval 0.0 to 10.0
|
0.88 score on a scale
Interval 0.0 to 10.0
|
3.52 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
1 hour
|
1.09 score on a scale
Interval 0.0 to 10.0
|
2.23 score on a scale
Interval 0.0 to 10.0
|
4.52 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
1.5 hours
|
1.29 score on a scale
Interval 0.0 to 10.0
|
2.43 score on a scale
Interval 0.0 to 10.0
|
3.1 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
2 hours
|
0.18 score on a scale
Interval 0.0 to 10.0
|
2.27 score on a scale
Interval 0.0 to 10.0
|
2.74 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
3 hours
|
0.54 score on a scale
Interval 0.0 to 10.0
|
0.62 score on a scale
Interval 0.0 to 10.0
|
0.16 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
6 hours
|
0.53 score on a scale
Interval 0.0 to 10.0
|
0.66 score on a scale
Interval 0.0 to 10.0
|
0.18 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
7 hours
|
0.76 score on a scale
Interval 0.0 to 10.0
|
0.65 score on a scale
Interval 0.0 to 10.0
|
0.12 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
4 hours
|
0.84 score on a scale
Interval 0.0 to 10.0
|
0.57 score on a scale
Interval 0.0 to 10.0
|
0.22 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
5 hours
|
0.40 score on a scale
Interval 0.0 to 10.0
|
0.49 score on a scale
Interval 0.0 to 10.0
|
0.22 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
8 hours
|
0.56 score on a scale
Interval 0.0 to 10.0
|
0.86 score on a scale
Interval 0.0 to 10.0
|
0.14 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling High/Intoxicated
24 hours
|
0.62 score on a scale
Interval 0.0 to 10.0
|
0.54 score on a scale
Interval 0.0 to 10.0
|
0.12 score on a scale
Interval 0.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hoursPopulation: 300mg and 500mg arm combined
Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Visual Analog Scale (VAS) - Drowsiness
1 hour
|
2.54 score on a scale
Interval 0.0 to 10.0
|
3.02 score on a scale
Interval 0.0 to 10.0
|
3.60 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
1.5 hours
|
2.58 score on a scale
Interval 0.0 to 10.0
|
3.96 score on a scale
Interval 0.0 to 10.0
|
4.50 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
4 hours
|
2.29 score on a scale
Interval 0.0 to 10.0
|
2.56 score on a scale
Interval 0.0 to 10.0
|
3.32 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
5 hours
|
1.10 score on a scale
Interval 0.0 to 10.0
|
1.86 score on a scale
Interval 0.0 to 10.0
|
2.50 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
8 hours
|
1.43 score on a scale
Interval 0.0 to 10.0
|
2.20 score on a scale
Interval 0.0 to 10.0
|
2.20 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
24 hours
|
1.80 score on a scale
Interval 0.0 to 10.0
|
1.00 score on a scale
Interval 0.0 to 10.0
|
2.68 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
baseline
|
1.43 score on a scale
Interval 0.0 to 10.0
|
2.14 score on a scale
Interval 0.0 to 10.0
|
2.46 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
0.5 hours
|
1.98 score on a scale
Interval 0.0 to 10.0
|
3.04 score on a scale
Interval 0.0 to 10.0
|
3.10 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
2 hours
|
1.97 score on a scale
Interval 0.0 to 10.0
|
3.86 score on a scale
Interval 0.0 to 10.0
|
4.72 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
3 hours
|
1.58 score on a scale
Interval 0.0 to 10.0
|
3.24 score on a scale
Interval 0.0 to 10.0
|
3.46 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
6 hours
|
1.86 score on a scale
Interval 0.0 to 10.0
|
1.73 score on a scale
Interval 0.0 to 10.0
|
0.96 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Drowsiness
7 hours
|
1.75 score on a scale
Interval 0.0 to 10.0
|
1.77 score on a scale
Interval 0.0 to 10.0
|
2.92 score on a scale
Interval 0.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hoursPopulation: 300mg and 500mg arm combined
Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Visual Analog Scale (VAS) - Anxiety
baseline
|
0.38 score on a scale
Interval 0.0 to 10.0
|
1.01 score on a scale
Interval 0.0 to 10.0
|
0.42 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
0.5 hours
|
0.33 score on a scale
Interval 0.0 to 10.0
|
0.79 score on a scale
Interval 0.0 to 10.0
|
2.58 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
1 hour
|
1 score on a scale
Interval 0.0 to 10.0
|
1.03 score on a scale
Interval 0.0 to 10.0
|
1.56 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
1.5 hours
|
0.59 score on a scale
Interval 0.0 to 10.0
|
0.76 score on a scale
Interval 0.0 to 10.0
|
0.70 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
3 hours
|
0.42 score on a scale
Interval 0.0 to 10.0
|
0.54 score on a scale
Interval 0.0 to 10.0
|
0.08 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
4 hours
|
0.38 score on a scale
Interval 0.0 to 10.0
|
0.55 score on a scale
Interval 0.0 to 10.0
|
0.28 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
5 hours
|
0.24 score on a scale
Interval 0.0 to 10.0
|
0.58 score on a scale
Interval 0.0 to 10.0
|
0.26 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
6 hours
|
0.28 score on a scale
Interval 0.0 to 10.0
|
0.51 score on a scale
Interval 0.0 to 10.0
|
0.20 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
7 hours
|
0.19 score on a scale
Interval 0.0 to 10.0
|
0.53 score on a scale
Interval 0.0 to 10.0
|
0.04 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
8 hours
|
0.17 score on a scale
Interval 0.0 to 10.0
|
0.62 score on a scale
Interval 0.0 to 10.0
|
0.12 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
24 hours
|
0.31 score on a scale
Interval 0.0 to 10.0
|
0.57 score on a scale
Interval 0.0 to 10.0
|
0.14 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Anxiety
2 hours
|
0.53 score on a scale
Interval 0.0 to 10.0
|
0.78 score on a scale
Interval 0.0 to 10.0
|
0.22 score on a scale
Interval 0.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hoursPopulation: 300mg and 500mg arm combined
Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Visual Analog Scale (VAS) - Depressed Mood
0.5 hours
|
1.18 score on a scale
Interval 0.0 to 10.0
|
0.41 score on a scale
Interval 0.0 to 10.0
|
0.16 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
1 hour
|
0.26 score on a scale
Interval 0.0 to 10.0
|
0.28 score on a scale
Interval 0.0 to 10.0
|
0.46 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
1.5 hours
|
0.28 score on a scale
Interval 0.0 to 10.0
|
0.44 score on a scale
Interval 0.0 to 10.0
|
0.24 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
2 hours
|
0.64 score on a scale
Interval 0.0 to 10.0
|
0.38 score on a scale
Interval 0.0 to 10.0
|
0.10 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
3 hours
|
0.22 score on a scale
Interval 0.0 to 10.0
|
0.36 score on a scale
Interval 0.0 to 10.0
|
0.14 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
4 hours
|
0.24 score on a scale
Interval 0.0 to 10.0
|
0.38 score on a scale
Interval 0.0 to 10.0
|
0.28 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
5 hours
|
0.22 score on a scale
Interval 0.0 to 10.0
|
0.28 score on a scale
Interval 0.0 to 10.0
|
0.84 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
6 hours
|
0.20 score on a scale
Interval 0.0 to 10.0
|
0.18 score on a scale
Interval 0.0 to 10.0
|
0.16 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
8 hours
|
0.20 score on a scale
Interval 0.0 to 10.0
|
0.31 score on a scale
Interval 0.0 to 10.0
|
0.16 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
24 hours
|
0.20 score on a scale
Interval 0.0 to 10.0
|
0.33 score on a scale
Interval 0.0 to 10.0
|
0.12 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
baseline
|
0.19 score on a scale
Interval 0.0 to 10.0
|
0.33 score on a scale
Interval 0.0 to 10.0
|
0.38 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Depressed Mood
7 hours
|
0.31 score on a scale
Interval 0.0 to 10.0
|
0.29 score on a scale
Interval 0.0 to 10.0
|
0.12 score on a scale
Interval 0.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hoursPopulation: 300mg and 500mg arm combined
Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Visual Analog Scale (VAS) - Happy Mood
baseline
|
6.13 score on a scale
Interval 0.0 to 10.0
|
5.22 score on a scale
Interval 0.0 to 10.0
|
5.60 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
0.5 hours
|
5.73 score on a scale
Interval 0.0 to 10.0
|
4.28 score on a scale
Interval 0.0 to 10.0
|
5.50 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
1 hour
|
5.63 score on a scale
Interval 0.0 to 10.0
|
4.27 score on a scale
Interval 0.0 to 10.0
|
4.80 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
3 hours
|
5.43 score on a scale
Interval 0.0 to 10.0
|
3.98 score on a scale
Interval 0.0 to 10.0
|
4.12 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
4 hours
|
5.70 score on a scale
Interval 0.0 to 10.0
|
4.50 score on a scale
Interval 0.0 to 10.0
|
5.22 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
5 hours
|
5.10 score on a scale
Interval 0.0 to 10.0
|
4.34 score on a scale
Interval 0.0 to 10.0
|
4.20 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
7 hours
|
5.37 score on a scale
Interval 0.0 to 10.0
|
4.17 score on a scale
Interval 0.0 to 10.0
|
4.32 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
8 hours
|
5.70 score on a scale
Interval 0.0 to 10.0
|
4.19 score on a scale
Interval 0.0 to 10.0
|
4.36 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
24 hours
|
5.84 score on a scale
Interval 0.0 to 10.0
|
4.85 score on a scale
Interval 0.0 to 10.0
|
4.84 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
1.5 hours
|
4.90 score on a scale
Interval 0.0 to 10.0
|
4.45 score on a scale
Interval 0.0 to 10.0
|
3.94 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
2 hours
|
5.34 score on a scale
Interval 0.0 to 10.0
|
3.83 score on a scale
Interval 0.0 to 10.0
|
3.72 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Happy Mood
6 hours
|
5.07 score on a scale
Interval 0.0 to 10.0
|
4.39 score on a scale
Interval 0.0 to 10.0
|
5.02 score on a scale
Interval 0.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hoursPopulation: 300mg and 500mg arm combined
Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Visual Analog Scale (VAS) - Excitement
baseline
|
2.55 score on a scale
Interval 0.0 to 10.0
|
2.12 score on a scale
Interval 0.0 to 10.0
|
3.90 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
1 hour
|
2.66 score on a scale
Interval 0.0 to 10.0
|
2.10 score on a scale
Interval 0.0 to 10.0
|
3.46 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
1.5 hours
|
1.53 score on a scale
Interval 0.0 to 10.0
|
1.89 score on a scale
Interval 0.0 to 10.0
|
2.48 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
2 hours
|
2.37 score on a scale
Interval 0.0 to 10.0
|
2.02 score on a scale
Interval 0.0 to 10.0
|
2.92 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
6 hours
|
3.21 score on a scale
Interval 0.0 to 10.0
|
1.42 score on a scale
Interval 0.0 to 10.0
|
2.36 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
7 hours
|
2.54 score on a scale
Interval 0.0 to 10.0
|
1.02 score on a scale
Interval 0.0 to 10.0
|
2.68 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
8 hours
|
2.58 score on a scale
Interval 0.0 to 10.0
|
1.39 score on a scale
Interval 0.0 to 10.0
|
2.70 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
24 hours
|
4.01 score on a scale
Interval 0.0 to 10.0
|
2.35 score on a scale
Interval 0.0 to 10.0
|
2.98 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
0.5 hours
|
2.35 score on a scale
Interval 0.0 to 10.0
|
1.44 score on a scale
Interval 0.0 to 10.0
|
3.92 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
3 hours
|
2.50 score on a scale
Interval 0.0 to 10.0
|
1.65 score on a scale
Interval 0.0 to 10.0
|
3.16 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
4 hours
|
2.49 score on a scale
Interval 0.0 to 10.0
|
2.29 score on a scale
Interval 0.0 to 10.0
|
2.76 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Excitement
5 hours
|
2.25 score on a scale
Interval 0.0 to 10.0
|
2.17 score on a scale
Interval 0.0 to 10.0
|
2.16 score on a scale
Interval 0.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hoursPopulation: 300mg and 500mg arm combined
Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Visual Analog Scale (VAS) - Feeling of Control
baseline
|
4.00 score on a scale
Interval 0.0 to 10.0
|
3.27 score on a scale
Interval 0.0 to 10.0
|
3.24 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
0.5 hours
|
3.84 score on a scale
Interval 0.0 to 10.0
|
2.00 score on a scale
Interval 0.0 to 10.0
|
5.46 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
1 hour
|
3.14 score on a scale
Interval 0.0 to 10.0
|
3.81 score on a scale
Interval 0.0 to 10.0
|
3.96 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
1.5 hours
|
3.39 score on a scale
Interval 0.0 to 10.0
|
1.91 score on a scale
Interval 0.0 to 10.0
|
4.04 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
2 hours
|
3.48 score on a scale
Interval 0.0 to 10.0
|
3.07 score on a scale
Interval 0.0 to 10.0
|
4.24 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
3 hours
|
4.13 score on a scale
Interval 0.0 to 10.0
|
2.17 score on a scale
Interval 0.0 to 10.0
|
3.56 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
5 hours
|
3.07 score on a scale
Interval 0.0 to 10.0
|
2.51 score on a scale
Interval 0.0 to 10.0
|
3.48 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
6 hours
|
3.75 score on a scale
Interval 0.0 to 10.0
|
2.14 score on a scale
Interval 0.0 to 10.0
|
4.44 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
8 hours
|
3.83 score on a scale
Interval 0.0 to 10.0
|
2.11 score on a scale
Interval 0.0 to 10.0
|
4.56 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
24 hours
|
3.94 score on a scale
Interval 0.0 to 10.0
|
3.52 score on a scale
Interval 0.0 to 10.0
|
5.30 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
4 hours
|
4.22 score on a scale
Interval 0.0 to 10.0
|
2.87 score on a scale
Interval 0.0 to 10.0
|
3.56 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Feeling of Control
7 hours
|
3.76 score on a scale
Interval 0.0 to 10.0
|
1.80 score on a scale
Interval 0.0 to 10.0
|
4.50 score on a scale
Interval 0.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hoursPopulation: 300mg and 500mg arm combined
Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Visual Analog Scale (VAS) - Vividness of Image
baseline
|
5.34 score on a scale
Interval 0.0 to 10.0
|
2.99 score on a scale
Interval 0.0 to 10.0
|
2.10 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
0.5 hours
|
5.03 score on a scale
Interval 0.0 to 10.0
|
2.42 score on a scale
Interval 0.0 to 10.0
|
3.50 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
1 hour
|
5.17 score on a scale
Interval 0.0 to 10.0
|
2.94 score on a scale
Interval 0.0 to 10.0
|
4.24 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
1.5 hours
|
5.21 score on a scale
Interval 0.0 to 10.0
|
2.75 score on a scale
Interval 0.0 to 10.0
|
3.76 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
2 hours
|
5.33 score on a scale
Interval 0.0 to 10.0
|
2.57 score on a scale
Interval 0.0 to 10.0
|
3.24 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
3 hours
|
5.82 score on a scale
Interval 0.0 to 10.0
|
2.76 score on a scale
Interval 0.0 to 10.0
|
2.04 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
5 hours
|
5.78 score on a scale
Interval 0.0 to 10.0
|
2.45 score on a scale
Interval 0.0 to 10.0
|
2.02 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
8 hours
|
5.94 score on a scale
Interval 0.0 to 10.0
|
2.39 score on a scale
Interval 0.0 to 10.0
|
2.50 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
4 hours
|
5.70 score on a scale
Interval 0.0 to 10.0
|
2.61 score on a scale
Interval 0.0 to 10.0
|
2.32 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
6 hours
|
5.72 score on a scale
Interval 0.0 to 10.0
|
2.21 score on a scale
Interval 0.0 to 10.0
|
2.58 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
7 hours
|
5.70 score on a scale
Interval 0.0 to 10.0
|
2.17 score on a scale
Interval 0.0 to 10.0
|
2.16 score on a scale
Interval 0.0 to 10.0
|
—
|
|
Visual Analog Scale (VAS) - Vividness of Image
24 hours
|
5.91 score on a scale
Interval 0.0 to 10.0
|
2.45 score on a scale
Interval 0.0 to 10.0
|
2.20 score on a scale
Interval 0.0 to 10.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, 2, 6, 7, 8, and 24 hoursPopulation: 300mg and 500mg arm combined
The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Composed-Anxious Scale
8 hours
|
32.7 score on a scale
Interval 0.0 to 36.0
|
29.2 score on a scale
Interval 0.0 to 36.0
|
31.4 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Composed-Anxious Scale
24 hours
|
33.1 score on a scale
Interval 0.0 to 36.0
|
29.3 score on a scale
Interval 0.0 to 36.0
|
33.0 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Composed-Anxious Scale
Baseline
|
33.9 score on a scale
Interval 0.0 to 36.0
|
29.3 score on a scale
Interval 0.0 to 36.0
|
33.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Composed-Anxious Scale
2 hours
|
31.7 score on a scale
Interval 0.0 to 36.0
|
28.5 score on a scale
Interval 0.0 to 36.0
|
29 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Composed-Anxious Scale
6 hours
|
31.9 score on a scale
Interval 0.0 to 36.0
|
30.7 score on a scale
Interval 0.0 to 36.0
|
33.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Composed-Anxious Scale
7 hours
|
33.5 score on a scale
Interval 0.0 to 36.0
|
29.1 score on a scale
Interval 0.0 to 36.0
|
32.8 score on a scale
Interval 0.0 to 36.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, 2, 6, 7, 8, and 24 hoursPopulation: 300mg and 500mg arm combined
The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Agreeable-Hostile Scale
Baseline
|
31.5 score on a scale
Interval 0.0 to 36.0
|
28.7 score on a scale
Interval 0.0 to 36.0
|
31.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Agreeable-Hostile Scale
2 hours
|
30.0 score on a scale
Interval 0.0 to 36.0
|
28.1 score on a scale
Interval 0.0 to 36.0
|
29.2 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Agreeable-Hostile Scale
7 hours
|
31.8 score on a scale
Interval 0.0 to 36.0
|
27.0 score on a scale
Interval 0.0 to 36.0
|
30.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Agreeable-Hostile Scale
8 hours
|
32.2 score on a scale
Interval 0.0 to 36.0
|
27.7 score on a scale
Interval 0.0 to 36.0
|
30.0 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Agreeable-Hostile Scale
6 hours
|
31.1 score on a scale
Interval 0.0 to 36.0
|
28.1 score on a scale
Interval 0.0 to 36.0
|
30.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Agreeable-Hostile Scale
24 hours
|
33.0 score on a scale
Interval 0.0 to 36.0
|
27.6 score on a scale
Interval 0.0 to 36.0
|
29.8 score on a scale
Interval 0.0 to 36.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, 2, 6, 7, 8, and 24 hoursPopulation: 300mg and 500mg arm combined
The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Elated-Depression Scale
Baseline
|
29.1 score on a scale
Interval 0.0 to 36.0
|
25.6 score on a scale
Interval 0.0 to 36.0
|
27.0 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Elated-Depression Scale
2 hours
|
28.1 score on a scale
Interval 0.0 to 36.0
|
24.6 score on a scale
Interval 0.0 to 36.0
|
24.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Elated-Depression Scale
6 hours
|
29.0 score on a scale
Interval 0.0 to 36.0
|
25.8 score on a scale
Interval 0.0 to 36.0
|
27.2 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Elated-Depression Scale
7 hours
|
28.9 score on a scale
Interval 0.0 to 36.0
|
24.7 score on a scale
Interval 0.0 to 36.0
|
25.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Elated-Depression Scale
24 hours
|
31.4 score on a scale
Interval 0.0 to 36.0
|
25.5 score on a scale
Interval 0.0 to 36.0
|
26.0 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Elated-Depression Scale
8 hours
|
29.8 score on a scale
Interval 0.0 to 36.0
|
25.0 score on a scale
Interval 0.0 to 36.0
|
26.0 score on a scale
Interval 0.0 to 36.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, 2, 6, 7, 8, and 24 hoursPopulation: 300mg and 500mg arm combined
The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Confident-Unsure Scale
Baseline
|
27.4 score on a scale
Interval 0.0 to 36.0
|
24.3 score on a scale
Interval 0.0 to 36.0
|
27.4 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Confident-Unsure Scale
2 hours
|
24.8 score on a scale
Interval 0.0 to 36.0
|
22.6 score on a scale
Interval 0.0 to 36.0
|
21.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Confident-Unsure Scale
6 hours
|
26.5 score on a scale
Interval 0.0 to 36.0
|
24.5 score on a scale
Interval 0.0 to 36.0
|
22.4 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Confident-Unsure Scale
7 hours
|
27.1 score on a scale
Interval 0.0 to 36.0
|
22.9 score on a scale
Interval 0.0 to 36.0
|
23.4 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Confident-Unsure Scale
24 hours
|
29.0 score on a scale
Interval 0.0 to 36.0
|
24.6 score on a scale
Interval 0.0 to 36.0
|
26.0 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Confident-Unsure Scale
8 hours
|
27.0 score on a scale
Interval 0.0 to 36.0
|
23.2 score on a scale
Interval 0.0 to 36.0
|
24 score on a scale
Interval 0.0 to 36.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, 2, 6, 7, 8, and 24 hoursPopulation: 300mg and 500mg arm combined
The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Energetic-Tired Scale
Baseline
|
24.5 score on a scale
Interval 0.0 to 36.0
|
20.9 score on a scale
Interval 0.0 to 36.0
|
21.8 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Energetic-Tired Scale
2 hours
|
22.0 score on a scale
Interval 0.0 to 36.0
|
14.5 score on a scale
Interval 0.0 to 36.0
|
7.2 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Energetic-Tired Scale
6 hours
|
23.1 score on a scale
Interval 0.0 to 36.0
|
20.1 score on a scale
Interval 0.0 to 36.0
|
19.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Energetic-Tired Scale
7 hours
|
23.5 score on a scale
Interval 0.0 to 36.0
|
20.2 score on a scale
Interval 0.0 to 36.0
|
16.2 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Energetic-Tired Scale
8 hours
|
26.1 score on a scale
Interval 0.0 to 36.0
|
20.5 score on a scale
Interval 0.0 to 36.0
|
19.4 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Energetic-Tired Scale
24 hours
|
29.3 score on a scale
Interval 0.0 to 36.0
|
24.0 score on a scale
Interval 0.0 to 36.0
|
20.8 score on a scale
Interval 0.0 to 36.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, 2, 6, 7, 8, and 24 hoursPopulation: 300mg and 500mg arm combined
The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Clearheaded-Confused Scale
Baseline
|
31.1 score on a scale
Interval 0.0 to 36.0
|
27.9 score on a scale
Interval 0.0 to 36.0
|
31.2 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Clearheaded-Confused Scale
2 hours
|
29.0 score on a scale
Interval 0.0 to 36.0
|
24.7 score on a scale
Interval 0.0 to 36.0
|
22.2 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Clearheaded-Confused Scale
6 hours
|
30.3 score on a scale
Interval 0.0 to 36.0
|
27.5 score on a scale
Interval 0.0 to 36.0
|
29.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Clearheaded-Confused Scale
7 hours
|
30.6 score on a scale
Interval 0.0 to 36.0
|
26.9 score on a scale
Interval 0.0 to 36.0
|
27.8 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Clearheaded-Confused Scale
8 hours
|
31.2 score on a scale
Interval 0.0 to 36.0
|
26.6 score on a scale
Interval 0.0 to 36.0
|
28.6 score on a scale
Interval 0.0 to 36.0
|
—
|
|
Profile of Mood States Bipolar Scale (POMS-Bi): Clearheaded-Confused Scale
24 hours
|
32.4 score on a scale
Interval 0.0 to 36.0
|
28.3 score on a scale
Interval 0.0 to 36.0
|
30.0 score on a scale
Interval 0.0 to 36.0
|
—
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: 300mg and 500mg arm combined
The PSS is a 10-item self-report scale that measures the perception of stress. Each item is rated on a scale from 0-4. Full scale from 0-40, with higher score indicating more perceived stress
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Perceived Stress Scale (PSS)
Baseline
|
5.7 score on a scale
Interval 0.0 to 40.0
|
7.1 score on a scale
Interval 0.0 to 40.0
|
5.8 score on a scale
Interval 0.0 to 40.0
|
—
|
|
Perceived Stress Scale (PSS)
6 hours
|
6.8 score on a scale
Interval 0.0 to 40.0
|
7.2 score on a scale
Interval 0.0 to 40.0
|
4.8 score on a scale
Interval 0.0 to 40.0
|
—
|
|
Perceived Stress Scale (PSS)
7 hours
|
6.3 score on a scale
Interval 0.0 to 40.0
|
7.8 score on a scale
Interval 0.0 to 40.0
|
5.6 score on a scale
Interval 0.0 to 40.0
|
—
|
|
Perceived Stress Scale (PSS)
8 hours
|
5.7 score on a scale
Interval 0.0 to 40.0
|
8.5 score on a scale
Interval 0.0 to 40.0
|
5.2 score on a scale
Interval 0.0 to 40.0
|
—
|
|
Perceived Stress Scale (PSS)
24 hours
|
6.2 score on a scale
Interval 0.0 to 40.0
|
7.8 score on a scale
Interval 0.0 to 40.0
|
6.6 score on a scale
Interval 0.0 to 40.0
|
—
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: Participants given 300mg and 500mg were combined into one arm
The PRISE is a self-report Adverse Event (AE) Checklist used to qualify side effects by identifying and evaluating the tolerability of each symptom. Only new onset or worsening symptoms were included. Participants could report more than one AE.
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Patient Rated Inventory of Side Effects (PRISE)
Decreased energy
|
3 Participants
|
8 Participants
|
5 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Fatigue
|
4 Participants
|
9 Participants
|
3 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Dizziness
|
3 Participants
|
5 Participants
|
5 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Nausea/vomiting
|
0 Participants
|
5 Participants
|
5 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Anxiety
|
1 Participants
|
1 Participants
|
2 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Restlessness
|
2 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Palpitations
|
1 Participants
|
2 Participants
|
1 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Dry mouth
|
2 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Sleeping too much
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Tremors
|
0 Participants
|
3 Participants
|
0 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
General malaise
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Difficulty sleeping
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Constipation
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Dizziness on standing
|
1 Participants
|
3 Participants
|
5 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Poor concentration
|
2 Participants
|
3 Participants
|
3 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Headache
|
2 Participants
|
4 Participants
|
1 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Poor coordination
|
1 Participants
|
3 Participants
|
2 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Blurred vision
|
0 Participants
|
3 Participants
|
0 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Ringing in ears
|
0 Participants
|
0 Participants
|
2 Participants
|
—
|
|
Patient Rated Inventory of Side Effects (PRISE)
Increased perspiration
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, 2, 6, 7, 8, and 24 hoursPopulation: 300mg and 500mg arm combined
The BPRS is a 16-item clinician- administered scale that captures acute behavioral changes throughout treatment. Each item is rated on a scale from 1-7. Full scale from 16-112 with higher score indicating more worse health outcomes.
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Brief Psychiatric Rating Scale (BPRS)
Baseline
|
16 score on a scale
Interval 16.0 to 112.0
|
16.1 score on a scale
Interval 16.0 to 112.0
|
16 score on a scale
Interval 16.0 to 112.0
|
—
|
|
Brief Psychiatric Rating Scale (BPRS)
2 hours
|
16 score on a scale
Interval 16.0 to 112.0
|
16.3 score on a scale
Interval 16.0 to 112.0
|
16 score on a scale
Interval 16.0 to 112.0
|
—
|
|
Brief Psychiatric Rating Scale (BPRS)
6 hours
|
16 score on a scale
Interval 16.0 to 112.0
|
16 score on a scale
Interval 16.0 to 112.0
|
16 score on a scale
Interval 16.0 to 112.0
|
—
|
|
Brief Psychiatric Rating Scale (BPRS)
7 hours
|
16 score on a scale
Interval 16.0 to 112.0
|
16 score on a scale
Interval 16.0 to 112.0
|
16 score on a scale
Interval 16.0 to 112.0
|
—
|
|
Brief Psychiatric Rating Scale (BPRS)
8 hours
|
16 score on a scale
Interval 16.0 to 112.0
|
16 score on a scale
Interval 16.0 to 112.0
|
16 score on a scale
Interval 16.0 to 112.0
|
—
|
|
Brief Psychiatric Rating Scale (BPRS)
24 hours
|
16 score on a scale
Interval 16.0 to 112.0
|
16 score on a scale
Interval 16.0 to 112.0
|
16 score on a scale
Interval 16.0 to 112.0
|
—
|
SECONDARY outcome
Timeframe: 24 hoursThe C-SSRS is a clinician-administered suicidal ideation and behavior rating scale used to evaluate suicide risk. Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation).
Outcome measures
| Measure |
Harmine Hydrochloride 100mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 300mg
n=5 Participants
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 500mg
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|---|
|
Columbia Suicide Severity Rating Scale (C-SSRS)
|
0 score on a scale
Interval 0.0 to 9.0
|
0 score on a scale
Interval 0.0 to 9.0
|
0 score on a scale
Interval 0.0 to 9.0
|
—
|
Adverse Events
Harmine Hydrochloride 100mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Harmine Hydrochloride 200mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Harmine Hydrochloride >200mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Harmine Hydrochloride 100mg
n=10 participants at risk
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride 200mg
n=10 participants at risk
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
Harmine Hydrochloride >200mg
n=5 participants at risk
Using the CRM to inform the dose to be given to the next participant based on prior information. The CRM used a one-parameter logistic regression model to estimate the relationship between dose and dose-limiting toxicity (DLT) risk to inform decisions on dosing with a target DLT rate of 25%. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a participant experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. At every step, the next patient is assigned the dose estimated to be nearest to the MTD. To minimize the exposure of participants to potentially toxic doses, we employed some modifications to the CRM, including starting with the lowest dose available and not skipping dose levels when escalating. Additionally, we included an early stopping rule that the study would end when either the maximum number of allowable patients treated per protocol was reached or would end early in the event that the probability of the next 10 patients being given the same dose level exceeds 90%, regardless of DLT outcomes observed.
Each participant received a single oral dose of harmine HCl on the treatment day and was observed for 8 h with continuous medical monitoring and followed up at 24 h. Note that doses \>500 mg were not used due to the stopping rule above.
|
|---|---|---|---|
|
Gastrointestinal disorders
Vomiting/emesis
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
30.0%
3/10 • 24 hours
300mg and 500mg arm combined
|
100.0%
5/5 • 24 hours
300mg and 500mg arm combined
|
|
Nervous system disorders
Dizziness
|
20.0%
2/10 • 24 hours
300mg and 500mg arm combined
|
10.0%
1/10 • 24 hours
300mg and 500mg arm combined
|
20.0%
1/5 • 24 hours
300mg and 500mg arm combined
|
|
Nervous system disorders
Impaired concentration/confusion
|
10.0%
1/10 • 24 hours
300mg and 500mg arm combined
|
30.0%
3/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/5 • 24 hours
300mg and 500mg arm combined
|
|
Nervous system disorders
Drowsiness
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
30.0%
3/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/5 • 24 hours
300mg and 500mg arm combined
|
|
Nervous system disorders
Visual illusion
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
10.0%
1/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/5 • 24 hours
300mg and 500mg arm combined
|
|
Nervous system disorders
Auditory hallucination
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
20.0%
1/5 • 24 hours
300mg and 500mg arm combined
|
|
Nervous system disorders
Giddiness
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
20.0%
1/5 • 24 hours
300mg and 500mg arm combined
|
|
Cardiac disorders
Hypotension
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
20.0%
1/5 • 24 hours
300mg and 500mg arm combined
|
|
Nervous system disorders
Vasovagal
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
20.0%
1/5 • 24 hours
300mg and 500mg arm combined
|
|
Nervous system disorders
Tingling
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
10.0%
1/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/5 • 24 hours
300mg and 500mg arm combined
|
|
Nervous system disorders
Numbness
|
10.0%
1/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/5 • 24 hours
300mg and 500mg arm combined
|
|
General disorders
Fatigue
|
10.0%
1/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/5 • 24 hours
300mg and 500mg arm combined
|
|
Gastrointestinal disorders
Nausea w/o vomiting
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
10.0%
1/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/5 • 24 hours
300mg and 500mg arm combined
|
|
General disorders
Heaviness
|
10.0%
1/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/10 • 24 hours
300mg and 500mg arm combined
|
0.00%
0/5 • 24 hours
300mg and 500mg arm combined
|
Additional Information
Jessica L Ables
Icahn School of Medicine at Mount Sinai
Phone: (212) 241-2774
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place