Trial Outcomes & Findings for JOTROL PK, Safety, and Food Effect Assessment (NCT NCT04668274)
NCT ID: NCT04668274
Last Updated: 2022-08-12
Results Overview
An adverse event (AE) was defined as any untoward medical occurrence (including clinically significant \[CS\] vital signs measurements or laboratory results) or worsening of a pre-existing condition in a participant administered a pharmaceutical product during the course of the study, whether related or not to the study medication. TEAEs were defined as AE that occurred on or after the date and time of study drug administration or those that first occurred pre-dose but worsened by increase in occurrence or severity after study drug administration. TEAEs includes both serious and non-serious TEAEs.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
From first dose of study drug administration up to 131 days
Results posted on
2022-08-12
Participant Flow
Participants took part in the study at 1 investigative site in the United States from 21 January 2021 to 31 May 2021.
A total of 83 healthy participants were screened, of which 29 participants were eligible for this study. Of 29 eligible participants, a total of 24 participants were treated in this single ascending dose study.
Participant milestones
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
Participants received JOTROL (resveratrol) 200 (2\*100) milligram (mg) (Treatment A), gelatin capsule (gelcap), orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A 14 days washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A 14 days washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A 14 days washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Part 1 Study Period 1
STARTED
|
21
|
0
|
0
|
0
|
|
Part 1 Study Period 1
COMPLETED
|
16
|
0
|
0
|
0
|
|
Part 1 Study Period 1
NOT COMPLETED
|
5
|
0
|
0
|
0
|
|
Part 1 Study Period 2
STARTED
|
0
|
16
|
0
|
0
|
|
Part 1 Study Period 2
COMPLETED
|
0
|
15
|
0
|
0
|
|
Part 1 Study Period 2
NOT COMPLETED
|
0
|
1
|
0
|
0
|
|
Part 1 Study Period 3
STARTED
|
0
|
0
|
18
|
0
|
|
Part 1 Study Period 3
COMPLETED
|
0
|
0
|
15
|
0
|
|
Part 1 Study Period 3
NOT COMPLETED
|
0
|
0
|
3
|
0
|
|
Part 2 Study Period 4
STARTED
|
0
|
0
|
0
|
15
|
|
Part 2 Study Period 4
COMPLETED
|
0
|
0
|
0
|
14
|
|
Part 2 Study Period 4
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
Participants received JOTROL (resveratrol) 200 (2\*100) milligram (mg) (Treatment A), gelatin capsule (gelcap), orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A 14 days washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A 14 days washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A 14 days washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Part 1 Study Period 1
Adverse Event
|
3
|
0
|
0
|
0
|
|
Part 1 Study Period 1
Withdrawal by Subject
|
2
|
0
|
0
|
0
|
|
Part 1 Study Period 2
Other
|
0
|
1
|
0
|
0
|
|
Part 1 Study Period 3
Adverse Event
|
0
|
0
|
1
|
0
|
|
Part 1 Study Period 3
Other
|
0
|
0
|
2
|
0
|
|
Part 2 Study Period 4
Other
|
0
|
0
|
0
|
1
|
Baseline Characteristics
JOTROL PK, Safety, and Food Effect Assessment
Baseline characteristics by cohort
| Measure |
All Participants
n=24 Participants
All participants who received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A) gelcap, orally once on Day 1 in Study period 1 followed by 500 (5\*100) mg (Treatment B) gelcap, orally once on Day 1 in Study period 2 further followed by 700 (7\*100) mg (Treatment C) gelcap, orally, on Day 1 in Study period 3 in fasted conditions of Part 1 of the study, followed by JOTROL (resveratrol) 500 (5\*100) mg (Treatment D) gelcap, orally, once on Day 1 in fed condition in Study Period 4 of Part 2 of the study. There was a washout period of 14 days between each study period.
|
|---|---|
|
Age, Continuous
|
48.7 years
STANDARD_DEVIATION 12.6 • n=99 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
24 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: From first dose of study drug administration up to 131 daysPopulation: The safety population was defined as all participants who received at least one dose of the study medication.
An adverse event (AE) was defined as any untoward medical occurrence (including clinically significant \[CS\] vital signs measurements or laboratory results) or worsening of a pre-existing condition in a participant administered a pharmaceutical product during the course of the study, whether related or not to the study medication. TEAEs were defined as AE that occurred on or after the date and time of study drug administration or those that first occurred pre-dose but worsened by increase in occurrence or severity after study drug administration. TEAEs includes both serious and non-serious TEAEs.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=21 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=16 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=18 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
n=15 Participants
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
7 Participants
|
4 Participants
|
6 Participants
|
6 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: The pharmacokinetic (PK) population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. "Number analyzed" signifies to participants evaluable for given categories.
AUC(0-infinity) of resveratrol, resveratrol-3-glucuronide, resveratrol-4'-glucuronide, and resveratrol-3-sulfate in plasma were reported. AUC(0-infinity) of resveratrol, resveratrol-3-glucuronide, resveratrol-4'-glucuronide, and resveratrol-3-sulfate in plasma were reported and calculated as AUC0-t + Ct/Kel, where Ct is the last observed measurable concentration, AUC0-t is Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration and Kel is Elimination rate constant.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=21 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=16 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=18 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
n=14 Participants
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol-4'-Glucuronide
|
4591.06 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 27.34
|
15387.06 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 29.76
|
22934.42 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 29.90
|
14528.02 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 21.95
|
|
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol
|
214.73 hour*nanogram per milliliter (h*ng/mL)
|
499.73 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 56.54
|
595.75 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 28.19
|
553.77 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 60.84
|
|
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol-3-Glucuronide
|
4821.18 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 29.37
|
16390.55 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 27.25
|
29570.84 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 34.08
|
11834.05 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 28.41
|
|
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity (AUC0-inf) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol-3-Sulfate
|
11668.98 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 27.75
|
35063.90 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 31.67
|
53845.25 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 20.62
|
31133.94 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 33.24
|
PRIMARY outcome
Timeframe: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration.
AUC0-t was Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration. AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=21 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=16 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=18 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
n=14 Participants
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol
|
112.32 h*ng/mL
Geometric Coefficient of Variation 72.49
|
422.85 h*ng/mL
Geometric Coefficient of Variation 53.24
|
785.29 h*ng/mL
Geometric Coefficient of Variation 51.52
|
263.75 h*ng/mL
Geometric Coefficient of Variation 65.72
|
|
Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol-3-Glucuronide
|
4796.08 h*ng/mL
Geometric Coefficient of Variation 29.58
|
16347.62 h*ng/mL
Geometric Coefficient of Variation 27.21
|
29492.22 h*ng/mL
Geometric Coefficient of Variation 34.04
|
11775.27 h*ng/mL
Geometric Coefficient of Variation 28.51
|
|
Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol-3-Sulfate
|
11593.20 h*ng/mL
Geometric Coefficient of Variation 26.78
|
34854.48 h*ng/mL
Geometric Coefficient of Variation 31.49
|
53351.47 h*ng/mL
Geometric Coefficient of Variation 20.04
|
31018.49 h*ng/mL
Geometric Coefficient of Variation 33.26
|
|
Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol-4'-Glucuronide
|
4550.27 h*ng/mL
Geometric Coefficient of Variation 27.58
|
15337.45 h*ng/mL
Geometric Coefficient of Variation 29.70
|
22845.47 h*ng/mL
Geometric Coefficient of Variation 29.36
|
14502.21 h*ng/mL
Geometric Coefficient of Variation 21.93
|
PRIMARY outcome
Timeframe: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration.
Cmax was the maximum observed plasma concentration obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=21 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=16 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=18 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
n=14 Participants
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol
|
94.70 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 91.46
|
326.32 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 89.76
|
648.08 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 73.29
|
140.09 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 100.84
|
|
Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol-3-Glucuronide
|
2292.84 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 29.69
|
8334.08 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 48.84
|
14558.05 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 46.33
|
4173.48 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 59.28
|
|
Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol-3-Sulfate
|
6204.37 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 36.00
|
16863.57 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 48.55
|
22856.79 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 27.23
|
10696.58 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 65.43
|
|
Maximum Observed Plasma Concentration (Cmax) for Resveratrol and Its Metabolites (Resveratrol-3-glucuronide, Resveratrol-4'-Glucuronide, and Resveratrol-3-sulfate)
Resveratrol-4'-Glucuronide
|
1649.08 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 33.30
|
5340.95 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 56.63
|
7663.09 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 40.20
|
3742.71 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 48.44
|
SECONDARY outcome
Timeframe: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. Here "overall number of participants analyzed" included all participants who were evaluable for this outcome measure.
Residual area for resveratrol in plasma was calculated and reported. The residual area was calculated as 100\*(1- AUC0-t / AUC0-inf) where AUC0-t (h\*ng/mL) = area under the concentration-time curve from time zero to the last measurable concentration and AUC0-inf (h\*ng/mL) = area under the plasma concentration-time curve from time 0 to time of infinity.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=1 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=5 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=3 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
n=2 Participants
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Residual Area for Resveratrol
|
5.48 percentage AUC
|
4.56 percentage AUC
Geometric Coefficient of Variation 73.50
|
3.58 percentage AUC
Geometric Coefficient of Variation 38.56
|
2.29 percentage AUC
Geometric Coefficient of Variation 111.16
|
SECONDARY outcome
Timeframe: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration.
Tmax was time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=21 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=16 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=18 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
n=14 Participants
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax) for Resveratrol
|
0.999 hour
Interval 0.25 to 2.006
|
1.003 hour
Interval 0.496 to 2.001
|
1.025 hour
Interval 0.251 to 2.0
|
1.497 hour
Interval 0.499 to 2.002
|
SECONDARY outcome
Timeframe: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. Here "overall number of participants analyzed" included all participants who were evaluable for this outcome measure.
Elimination half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=1 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=5 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=3 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
n=2 Participants
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Elimination Half-Life (T1/2 el) for Resveratrol
|
1.26 hour
|
2.36 hour
Geometric Coefficient of Variation 62.56
|
1.56 hour
Geometric Coefficient of Variation 25.19
|
1.47 hour
Geometric Coefficient of Variation 71.72
|
SECONDARY outcome
Timeframe: Pre-dose and 0.133, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. Here "overall number of participants analyzed" included all participants who were evaluable for this outcome measure.
Kel was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=1 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=5 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=3 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
n=2 Participants
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Elimination Rate Constant (Kel) for Resveratrol
|
0.5520 1 per hour (1/h)
|
0.2932 1 per hour (1/h)
Geometric Coefficient of Variation 48.70
|
0.4436 1 per hour (1/h)
Geometric Coefficient of Variation 28.56
|
0.4712 1 per hour (1/h)
Geometric Coefficient of Variation 71.72
|
SECONDARY outcome
Timeframe: Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. As pre-specified, this outcome measure was planned to be assessed for Part 1 only.
Cumulative urinary excretion from time zero to time t, calculated as the sum of the amounts excreted over each collection interval. The amount excreted in urine for each time interval was calculated as the urine concentration multiplied by the urine volume.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=21 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=16 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=18 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for Resveratrol
|
16927.35 nanogram (ng)
Geometric Coefficient of Variation 75.39
|
48454.76 nanogram (ng)
Geometric Coefficient of Variation 49.88
|
109323.50 nanogram (ng)
Geometric Coefficient of Variation 88.32
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. As pre-specified, this outcome measure was planned to be assessed for Part 1 only.
Maximum rate of urinary excretion, calculated by dividing the amount of drug excreted in each collection interval by the time over which it was collected.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=21 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=16 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=18 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Maximum Rate of Urinary Excretion (Rmax) for Resveratrol
|
8791.49 nanogram per hour (ng/h)
Geometric Coefficient of Variation 82.45
|
26486.23 nanogram per hour (ng/h)
Geometric Coefficient of Variation 136.58
|
44737.57 nanogram per hour (ng/h)
Geometric Coefficient of Variation 90.97
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. As pre-specified, this outcome measure was planned to be assessed for Part 1 only.
Tmax was the time after administration of a drug when the Rmax is reached.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=21 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=16 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=18 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Time of Rmax (Tmax) for Resveratrol
|
0.793 hour
Interval 0.233 to 12.013
|
0.551 hour
Interval 0.049 to 1.436
|
0.698 hour
Interval 0.29 to 3.563
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 4, 8, 12, 24, and 32 hours post-dose on Day 1Population: The PK population comprised of all participants who received at least one dose of either study drug and had at least one quantifiable PK concentration. As pre-specified, this outcome measure was planned to be assessed for Part 1 only.
CLr was calculated as Ae0-t/AUC0-t (plasma) where t is Tlast.
Outcome measures
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=21 Participants
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=16 Participants
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A-14 day washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=18 Participants
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A-14 day washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A-14 day washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Renal Clearance (CLr) for Resveratrol
|
0.15 liter per hour (L/h)
Geometric Coefficient of Variation 112.22
|
0.11 liter per hour (L/h)
Geometric Coefficient of Variation 63.04
|
0.14 liter per hour (L/h)
Geometric Coefficient of Variation 95.39
|
—
|
Adverse Events
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part 1: JOTROL (Resveratrol) 200 mg (Treatment A)
n=21 participants at risk
Participants received JOTROL (resveratrol) 200 (2\*100) mg (Treatment A), gelcap, orally, once on Day 1 in fasted conditions in Study Period 1.
|
Part 1: JOTROL (Resveratrol) 500 mg (Treatment B)
n=16 participants at risk
Participants who completed Study Period 1 received JOTROL (resveratrol) 500 (5\*100) mg (Treatment B), gelcap, orally, once on Day 1 in fasted conditions in Study Period 2. A 14 days washout period was maintained in study period 1 and 2.
|
Part 1: JOTROL (Resveratrol) 700 mg (Treatment C)
n=18 participants at risk
Participants who completed Study Period 2 received JOTROL (resveratrol) 700 (7\*100) mg (Treatment C), gelcap, orally, once on Day 1 in fasted conditions in Study Period 3. A 14 days washout period was maintained in study period 2 and 3.
|
Part 2: JOTROL (Resveratrol) 500 mg (Treatment D)
n=15 participants at risk
Participants who completed Study Period 3 (Part 1) received JOTROL (resveratrol) 500 (5\*100) mg (Treatment D), gelcap, orally, once on Day 1 in fed conditions in Study Period 4. A 14 days washout period was maintained in study period 3 and 4.
|
|---|---|---|---|---|
|
Nervous system disorders
Somnolence
|
14.3%
3/21 • From first dose of study drug administration up to 131 days
|
12.5%
2/16 • From first dose of study drug administration up to 131 days
|
11.1%
2/18 • From first dose of study drug administration up to 131 days
|
13.3%
2/15 • From first dose of study drug administration up to 131 days
|
|
Nervous system disorders
Headache
|
14.3%
3/21 • From first dose of study drug administration up to 131 days
|
12.5%
2/16 • From first dose of study drug administration up to 131 days
|
0.00%
0/18 • From first dose of study drug administration up to 131 days
|
0.00%
0/15 • From first dose of study drug administration up to 131 days
|
|
Nervous system disorders
Syncope
|
0.00%
0/21 • From first dose of study drug administration up to 131 days
|
0.00%
0/16 • From first dose of study drug administration up to 131 days
|
5.6%
1/18 • From first dose of study drug administration up to 131 days
|
0.00%
0/15 • From first dose of study drug administration up to 131 days
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/21 • From first dose of study drug administration up to 131 days
|
0.00%
0/16 • From first dose of study drug administration up to 131 days
|
0.00%
0/18 • From first dose of study drug administration up to 131 days
|
6.7%
1/15 • From first dose of study drug administration up to 131 days
|
|
Investigations
Blood pressure increased
|
0.00%
0/21 • From first dose of study drug administration up to 131 days
|
0.00%
0/16 • From first dose of study drug administration up to 131 days
|
5.6%
1/18 • From first dose of study drug administration up to 131 days
|
0.00%
0/15 • From first dose of study drug administration up to 131 days
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/21 • From first dose of study drug administration up to 131 days
|
0.00%
0/16 • From first dose of study drug administration up to 131 days
|
5.6%
1/18 • From first dose of study drug administration up to 131 days
|
0.00%
0/15 • From first dose of study drug administration up to 131 days
|
|
Investigations
SARS-CoV-2 test positive
|
0.00%
0/21 • From first dose of study drug administration up to 131 days
|
0.00%
0/16 • From first dose of study drug administration up to 131 days
|
5.6%
1/18 • From first dose of study drug administration up to 131 days
|
0.00%
0/15 • From first dose of study drug administration up to 131 days
|
|
Investigations
White blood cells urine
|
0.00%
0/21 • From first dose of study drug administration up to 131 days
|
0.00%
0/16 • From first dose of study drug administration up to 131 days
|
0.00%
0/18 • From first dose of study drug administration up to 131 days
|
6.7%
1/15 • From first dose of study drug administration up to 131 days
|
|
Gastrointestinal disorders
Diarrhoea
|
4.8%
1/21 • From first dose of study drug administration up to 131 days
|
0.00%
0/16 • From first dose of study drug administration up to 131 days
|
0.00%
0/18 • From first dose of study drug administration up to 131 days
|
0.00%
0/15 • From first dose of study drug administration up to 131 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/21 • From first dose of study drug administration up to 131 days
|
0.00%
0/16 • From first dose of study drug administration up to 131 days
|
0.00%
0/18 • From first dose of study drug administration up to 131 days
|
6.7%
1/15 • From first dose of study drug administration up to 131 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/21 • From first dose of study drug administration up to 131 days
|
0.00%
0/16 • From first dose of study drug administration up to 131 days
|
0.00%
0/18 • From first dose of study drug administration up to 131 days
|
6.7%
1/15 • From first dose of study drug administration up to 131 days
|
|
Infections and infestations
COVID-19
|
9.5%
2/21 • From first dose of study drug administration up to 131 days
|
0.00%
0/16 • From first dose of study drug administration up to 131 days
|
0.00%
0/18 • From first dose of study drug administration up to 131 days
|
0.00%
0/15 • From first dose of study drug administration up to 131 days
|
Additional Information
David Wyatt
Marshall A. Hayward, Ph.D., Jupiter Orphan Therapeutics Inc.
Phone: 305-547-5857
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place