Trial Outcomes & Findings for Study to Assess the Absorption, Metabolism, Excretion, and Mass Balance of CT1812 in Healthy Adult Male Subjects (NCT NCT05225389)

Results Overview

Plasma concentrations of CT1812 were determined using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

8 participants

Primary outcome timeframe

Predose through 96 hours postdose

Results posted on

2023-07-21

Participant Flow

Subjects were admitted to the clinical research unit (CRU).

Subjects were required to have a negative COVID-19 polymerase chain reaction (PCR) test in order to be enrolled in the study, as per the requirements outlined in the COVID-19 Clinical Pharmacology Unit Management Strategy and Study Risk Assessment documents.

Participant milestones

Participant milestones
Measure	300 mg Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Overall Study STARTED	8
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	300 mg Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Overall Study Three participants were discontinued by the Investigator on day 7 due to positive COVID-19 tests.	3

Baseline Characteristics

Study to Assess the Absorption, Metabolism, Excretion, and Mass Balance of CT1812 in Healthy Adult Male Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Age, Continuous	33.6 years STANDARD_DEVIATION 11.72 • n=99 Participants
Sex: Female, Male Female	0 Participants n=99 Participants
Sex: Female, Male Male	8 Participants n=99 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=99 Participants
Race/Ethnicity, Customized White	4 Participants n=99 Participants
Weight	81.91 Kg STANDARD_DEVIATION 12.908 • n=99 Participants
Height	180.3 cm STANDARD_DEVIATION 3.54 • n=99 Participants
Body Mass Index	25.233 kg/m^2 STANDARD_DEVIATION 3.5198 • n=99 Participants

PRIMARY outcome

Timeframe: Predose through 96 hours postdose

Population: For the calculation of summary statistics, values that are below the limit of quantitation (BLQ) of 0.00005 μg/mL are treated as 0.00 before the first quantifiable concentration and as missing elsewhere. No values were reported for the 120, 144, 168 hours timepoints. Three subjects were discontinued from the study after testing positive for COVID-19.

Plasma concentrations of CT1812 were determined using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects.

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Plasma CT1812 Concentration at 96 Hours Timepoint	0.0000707 μg/mL Standard Deviation 0.0000240

PRIMARY outcome

Timeframe: Predose through 144 hours postdose

Population: For the calculation of summary statistics, values that are below the limit of quantitation (BLQ) of 0.00005 μg/mL are treated as 0.00 before the first quantifiable concentration and as missing elsewhere. Three subjects were discontinued from the study after testing positive for COVID-19

Plasma concentrations of M6/CP199 were determined using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects.

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Plasma M6/CP199 Concentration at 144 Hours Timepoint	0.00001501 μg/mL Standard Deviation 0.0001370

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose

Population: For the calculation of summary statistics, values that are below the limits of quantitation (BLQ) ranging between 0.0261 - 0.0328 μg Eq/mL are treated as 0.00 before the first quantifiable concentration and as missing elsewhere. Three subjects were discontinued from the study after testing positive for COVID-19

Plasma Total Radioactivity Concentration of CT1812-Equivalents was performed using Liquid Scintillation Counting (LSC) method following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects.

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Plasma Total Radioactivity (TRA) Concentration CT1812-Equivalents at 168 Hours Timepoint	0.08720 μg Eq/mL Standard Deviation 0.068380

PRIMARY outcome

Timeframe: Predose through 144 hours postdose

Population: For the calculation of summary statistics, values that are below the limits of quantitation (BLQ) ranging between 0.0368 - 0.0406 μg Eq/mL are treated as 0.00 before the first quantifiable concentration and as missing elsewhere. Three subjects were discontinued from the study after testing positive for COVID-19. No values were reported at 168 hours timepoint.

The analysis of Whole Blood Total Radioactivity Concentration of CT1812-Equivalents was performed using combustion followed by Liquid Scintillation Counting (LSC) method following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects.

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Whole Blood Total Radioactivity (TRA) Concentration CT1812-Equivalents at 144 Hours Timepoint	0.04413 μg Eq/mL Standard Deviation 0.0086904

PRIMARY outcome

Timeframe: Predose and 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours postdose, and every 24 hours (pooled) until Day 8 (168 hours postdose).

Population: For the calculation of recovery parameters and summary statistics, concentration values that are below the limits.of quantitation (BLQ) ranging between 0.00205 to 0.00488 μg Eq/g are treated as 0.00. Three subjects were discontinued from the study after testing positive for COVID-19.

Cumulative radioactive dose (Cum%Dose) excreted in the urine was determined using Liquid Scintillation Counting (LSC) following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects.

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Cumulative Percentage of Radioactive Dose (Cum%Dose) Excreted in the Urine	81.13 percentage of radioactive eliminated Standard Deviation 2.9789

PRIMARY outcome

Timeframe: Predose, 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours postdose

Population: For the calculation of recovery parameters and summary statistics of concentration data, concentration values that are below the limits of quantitation (BLQ) are treated as 0.00. Three subjects were discontinued from the study after testing positive for COVID-19.

Cumulative radioactive dose (Cum%Dose) excreted in the feces was performed using combustion followed by Liquid Scintillation Counting (LSC) method following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects.

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Cumulative Percentage of Radioactive Dose (Cum%Dose) Excreted in the Feces	19.29 percentage of radioactive eliminated Standard Deviation 3,2123

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose

Plasma CT1812 Concentration were measured using the area under the concentration-time curve, from time 0 to the last observed non-zero concentration, as calculated by the linear trapezoidal method following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects. Plasma concentrations of CT1812 were determined using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
CT1812 Plasma Exposure According to AUC0-last Pharmacokinetic Parameter	0.6636 ug*hr/mL Standard Deviation 0.31014

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose

M6/CP199 Plasma Concentration was measured using the area under the concentration-time curve, from time 0 to the last observed non-zero concentration, as calculated by the linear trapezoidal method following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects. M6/CP199 plasma concentrations were determined using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
M6/CP199 Plasma Exposure According to AUC0-last Pharmacokinetic Parameter	48.46 ug*hr/mL) Standard Deviation 9.8619

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose

Plasma Total Radioactivity was measured using the area under the concentration-time curve, from time 0 to the last observed non-zero concentration, as calculated by the linear trapezoidal method following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects. Plasma Total Radioactivity Concentration of CT1812-Equivalents was performed using Liquid Scintillation Counting (LSC).

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Plasma Total Radioactivity According to AUC0-last Pharmacokinetic Parameter	85.24 μg Eq*hr/mL Standard Deviation 11.436

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose

Whole Blood Total Radioactivity was measured using the area under the concentration-time curve, from time 0 to the last observed non-zero concentration, as calculated by the linear trapezoidal method following a single oral dose of 300 mg (\~1 μCi) \[14C\]-CT1812 administered in healthy adult male subjects. Plasma Total Radioactivity Concentration of CT1812-Equivalents was performed using Liquid Scintillation Counting (LSC)

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Whole Blood Total Radioactivity According to AUC0-last Pharmacokinetic Parameter	52.51 μg Eq*hr/mL Standard Deviation 11.371

SECONDARY outcome

Timeframe: Predose through 144 hours postdose

This measure describes the percentage of TRA in whole blood relative to plasma. The fraction of \[14C\]-radioactivity associated with whole blood and plasma and with red blood cells and other cellular components of whole blood was determined by using the concentration of \[14C\]-radioactivity in whole blood and plasma.

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Whole Blood:Plasma Total Radioactivity Partitioning Ratios Over Time up to 144 Hours Timepoint	0.4519 ratio Standard Deviation 0.11051

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours

Population: Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).

Incidence and Severity of Adverse Events. All AEs that occurred during this clinical trial were coded using the Medical Dictionary for Regulatory Activities (MedDRA®), Version 24.1.

Outcome measures

Outcome measures
Measure	300 mg n=8 Participants Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs All TEAEs	5 Events
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs Mild TEAEs	3 Events
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs Moderate TEAEs	2 Events
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs Severe TEAEs	0 Events
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs Related TEAEs	0 Events
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs TEAEs Leading to Treatment Discontinuation	2 Events

Adverse Events

300 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	300 mg n=8 participants at risk Single oral dose of 300 mg CT1812 (2 capsules) with a microtracer dose of \~1 µCi \[14C\]-CT1812 (1 capsule).
Infections and infestations COVID 19	25.0% 2/8 • Number of events 2 • 15 days
Nervous system disorders Headache	12.5% 1/8 • Number of events 3 • 15 days

Additional Information

Chief Medical Officer, Head of R&D

Cogntion Therapeutics Inc

Phone: 914-221-6730

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Institution will not publish or present any Study Data, results, Study Inventions, or Sponsor Confidential Information without prior written approval from the Sponsor. Institution will keep confidential and not disclose any information provided by or on behalf of Sponsor or CRO or that is generated, discovered, or obtained by any Party as a result of the Study (other than patient medical records), including the Study results, Study Inventions and information related thereto.
Publication restrictions are in place

Restriction type: OTHER