Clinical trial NCT05225389: Study to Assess the Absorption, Metabolism, Excretion, and Mass Balance of CT1812 in Healthy Adult Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: Cognition Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Aging (NIA)
First posted: 2022-02-04
Enrollment: 8
Sex: MALE
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, single-dose study
Primary purpose: BASIC_SCIENCE

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)

Eligibility criteria: Inclusion Criteria:

1. Healthy, adult, male, 19 - 55 years of age
2. Male subjects must follow protocol specified contraception guidance as described in the protocol
3. Continuous non smoker who has not used tobacco/nicotine containing products for at least 3 months prior to dosing.
4. 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).
5. 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.
6. History of a minimum of 1 bowel movement per day.
7. Able to swallow multiple capsules.
8. Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

Exclusion Criteria:

1. Evidence of disease that, in the opinion of the PI/designee, may influence the outcome of the study within 4 weeks before dosing
2. 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.
3. Any history of GI surgery that may affect PK profiles of CT1812
4. Has evidence of a clinically significant abnormality in physical examination findings, vital signs, or clinical laboratory determinations at the Screening visit or Check-in.
5. Has a clinically significant ECG abnormality at the Screening visit or Check-in.
6. Estimated creatinine clearance \<80 ml/min/1.73 m2 at the Screening visit.
7. Known history of clinically significant allergy to CT1812 or excipients at the Screening visit.
8. 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.
9. Has a history of alcohol use disorder within the 2 years before the Screening visit.
10. Positive urine drug or alcohol results at the Screening visit or Check in.
11. Positive cotinine result at the Screening visit.
12. 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.
13. Donation of blood or significant blood loss within 56 days prior to dosing.
14. Plasma donation within 7 days prior to dosing.
15. Poor peripheral venous access.
16. Recent history (within 2 weeks of Day 1) of abnormal bowel movements, such as diarrhea, loose stools, or constipation.
17. 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.
18. 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.
19. Has previously participated in a CT1812 investigational study.
20. 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.
21. 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.
22. Participation in another clinical study within 30 days prior to dosing.

Primary outcomes:
measure: Plasma CT1812 Concentration at 96 Hours Timepoint
timeFrame: Predose through 96 hours postdose
measure: Plasma M6/CP199 Concentration at 144 Hours Timepoint
timeFrame: Predose through 144 hours postdose
measure: Plasma Total Radioactivity (TRA) Concentration CT1812-Equivalents at 168 Hours Timepoint
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose
measure: Whole Blood Total Radioactivity (TRA) Concentration CT1812-Equivalents at 144 Hours Timepoint
timeFrame: Predose through 144 hours postdose
measure: Cumulative Percentage of Radioactive Dose (Cum%Dose) Excreted in the Urine
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).
measure: Cumulative Percentage of Radioactive Dose (Cum%Dose) Excreted in the Feces
timeFrame: Predose, 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours postdose
measure: CT1812 Plasma Exposure According to AUC0-last Pharmacokinetic Parameter
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose
measure: M6/CP199 Plasma Exposure According to AUC0-last Pharmacokinetic Parameter
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose
measure: Plasma Total Radioactivity According to AUC0-last Pharmacokinetic Parameter
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose
measure: Whole Blood Total Radioactivity According to AUC0-last Pharmacokinetic Parameter
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours postdose
Secondary outcomes:
measure: Whole Blood:Plasma Total Radioactivity Partitioning Ratios Over Time up to 144 Hours Timepoint
timeFrame: Predose through 144 hours postdose
measure: Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 hours
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Cognition Therapeutics Inc.
name: Anthony Caggiano, MD
role: STUDY_DIRECTOR
References: