A Phase 1, Open-Label Study to Assess the Absorption, Metabolism, Excretion, and Mass Balance of a Single Oral Dose of [14C] CT1812 in Healthy Adult Male Subjects
Overview
- Phase
- Phase 1
- Intervention
- 300 mg [C14] CT1812
- Conditions
- Alzheimer Disease
- Sponsor
- Cognition Therapeutics
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Whole Blood Total Radioactivity According to AUC0-last Pharmacokinetic Parameter
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
Open-label, single-dose study to assess the absorption, metabolism, excretion and mass balance of [C14] CT1812
Detailed Description
Open-label, single-dose study to assess the absorption, metabolism, excretion and mass balance of \[C14\] CT1812 in 8 healthy male subjects Subjects will be screened 28-days prior to dosing to determine eligibility. Eligible subjects will be admitted to the clinical research unit (CRU) on Day -1. On Day 1, subjects will receive a single dose of CT1812 with a microtracer dose of \[14C\] CT1812. Whole blood, plasma, urine and fecal samples will be collection during the confinement period. Safety will be monitored throughout the study by repeated clinical and laboratory evaluations. Subjects will be and discharged from the CRU following completion of procedures 168 hours post dose (Day 8)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy, adult, male, 19 - 55 years of age
- •Male subjects must follow protocol specified contraception guidance as described in the protocol
- •Continuous non smoker who has not used tobacco/nicotine containing products for at least 3 months prior to dosing.
- •Body mass index (BMI) ≥18.0 and ≤30.0 kg/m2 at the Screening visit (subjects must not have experienced a weight loss or gain of \>10% within 4 weeks of dosing).
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI/designee at the Screening visit.
- •History of a minimum of 1 bowel movement per day.
- •Able to swallow multiple capsules.
- •Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.
Exclusion Criteria
- •Evidence of disease that, in the opinion of the PI/designee, may influence the outcome of the study within 4 weeks before dosing
- •Clinically significant illness, in the opinion of the PI/designee, that requires medical treatment within 8 weeks prior to dosing, or a clinically significant infection that requires medical treatment within 4 weeks prior to dosing.
- •Any history of GI surgery that may affect PK profiles of CT1812
- •Has evidence of a clinically significant abnormality in physical examination findings, vital signs, or clinical laboratory determinations at the Screening visit or Check-in.
- •Has a clinically significant ECG abnormality at the Screening visit or Check-in.
- •Estimated creatinine clearance \<80 ml/min/1.73 m2 at the Screening visit.
- •Known history of clinically significant allergy to CT1812 or excipients at the Screening visit.
- •Has been diagnosed with acquired immune deficiency syndrome, or tests positive for human immunodeficiency virus (HIV), Hepatitis B virus surface antigen (HBsAg), or Hepatitis C virus (HCV) at the Screening visit.
- •Has a history of alcohol use disorder within the 2 years before the Screening visit.
- •Positive urine drug or alcohol results at the Screening visit or Check in.
Arms & Interventions
CT1812
Investigational Drug
Intervention: 300 mg [C14] CT1812
Outcomes
Primary Outcomes
Whole Blood Total Radioactivity According to AUC0-last Pharmacokinetic Parameter
Time Frame: 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)
Plasma CT1812 Concentration at 96 Hours Timepoint
Time Frame: Predose through 96 hours postdose
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.
Plasma M6/CP199 Concentration at 144 Hours Timepoint
Time Frame: Predose through 144 hours postdose
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.
Whole Blood Total Radioactivity (TRA) Concentration CT1812-Equivalents at 144 Hours Timepoint
Time Frame: Predose through 144 hours postdose
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.
Plasma Total Radioactivity (TRA) Concentration CT1812-Equivalents at 168 Hours Timepoint
Time Frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose
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.
Cumulative Percentage of Radioactive Dose (Cum%Dose) Excreted in the Urine
Time Frame: 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).
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.
Cumulative Percentage of Radioactive Dose (Cum%Dose) Excreted in the Feces
Time Frame: Predose, 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours postdose
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.
CT1812 Plasma Exposure According to AUC0-last Pharmacokinetic Parameter
Time Frame: 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).
M6/CP199 Plasma Exposure According to AUC0-last Pharmacokinetic Parameter
Time Frame: 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).
Plasma Total Radioactivity According to AUC0-last Pharmacokinetic Parameter
Time Frame: 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).
Secondary Outcomes
- Whole Blood:Plasma Total Radioactivity Partitioning Ratios Over Time up to 144 Hours Timepoint(Predose through 144 hours postdose)
- Number of TEAEs, Related TEAEs, SAEs, and Related SAEs(Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours)