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

Study Overview
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Brief Summary
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Open-label, single-dose study to assess the absorption, metabolism, excretion and mass balance of [C14] CT1812

Detailed Description
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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)

Official Title
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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

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: 300 mg [C14] CT1812


Participation Criteria
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Eligibility Criteria
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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. Positive cotinine result at the Screening visit. Unable to refrain from or anticipates the use of: Any drugs, including prescription and non prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to dosing except for those allowed in the protocol Any drugs known to be significant inducers of CYP2D6 and CYP3A4 for 28 days prior to dosing. Donation of blood or significant blood loss within 56 days prior to dosing. Plasma donation within 7 days prior to dosing. Poor peripheral venous access. Recent history (within 2 weeks of Day 1) of abnormal bowel movements, such as diarrhea, loose stools, or constipation. Has exposure to significant diagnostic or therapeutic radiation (e.g., serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to Check-in. Has participated in a radiolabeled drug study where exposures are known to the PI within the previous 3 months prior to admission to the clinic for this study or participated in a radiolabeled drug study where exposures are not known to the PI within the previous 6 months prior to admission to the clinic for this study. Has previously participated in a CT1812 investigational study. Evidence or history of active suicidal thoughts in the 6 months preceding the screening visit; or have a history of a suicide attempt in the previous 2 years, or more than 1 lifetime suicide attempt; or are at serious suicide risk per the PIs clinical judgment. Has any condition that would, in the opinion of the PI/designee or Sponsor, make the subject unsuitable for the study or is, in the opinion of the PI/designee, not likely to complete the study for any reason. Participation in another clinical study within 30 days prior to dosing.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single-dose study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CT1812<br>Investigational Drug | Drug: 300 mg [C14] CT1812<br>* Single dose of 300 mg CT1812 with microtracer dose of [C14]<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma CT1812 Concentration at 96 Hours Timepoint | 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. | Predose through 96 hours postdose | 
| Plasma M6/CP199 Concentration at 144 Hours Timepoint | 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. | Predose through 144 hours postdose | 
| Plasma Total Radioactivity (TRA) Concentration CT1812-Equivalents at 168 Hours Timepoint | 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. | 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 (TRA) Concentration CT1812-Equivalents at 144 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. | Predose through 144 hours postdose | 
| Cumulative Percentage of Radioactive Dose (Cum%Dose) Excreted in the Urine | 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. | 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 Percentage of Radioactive Dose (Cum%Dose) Excreted in the Feces | 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. | Predose, 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours postdose | 
| CT1812 Plasma Exposure According to AUC0-last Pharmacokinetic Parameter | 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). | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose | 
| M6/CP199 Plasma Exposure According to AUC0-last Pharmacokinetic Parameter | 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). | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose | 
| Plasma Total Radioactivity According to AUC0-last Pharmacokinetic Parameter | 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). | 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 According to AUC0-last Pharmacokinetic Parameter | 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) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole Blood:Plasma Total Radioactivity Partitioning Ratios Over Time up to 144 Hours Timepoint | 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. | Predose through 144 hours postdose | 
| Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | 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. | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours |