Ascending Dose Study of CT1812 in Healthy Volunteers

Cognitive Impairment Clinical Trial

Official title: A Two-Part, Double-Blind, Placebo-Controlled, Phase I Study of the Safety Pharmacokinetics of Single and Multiple Ascending Doses of CT1812 in Healthy Volunteers

Status Completed

Clinical Trial Summary

This is a double-blind, placebo controlled, ascending dose, multi-cohort trial. The study will be conducted in two phases: a single ascending dose (SAD) phase "Part A", followed by a multiple ascending dose (MAD) phase "Part B". In Part A, subjects will receive one dose of study drug. In Part B, subjects within a cohort will receive the same dose daily for 14 days. In both parts, sequential cohorts will be exposed to increasing doses of CT1812 in order to identify the maximum tolerated dose (MTD).

Clinical Trial Description

Part A - Single Ascending Dose in up to 54 Subjects

Screening procedures will occur on Days -21 to -3. Subjects will be admitted to the clinical research unit for up to 5 days. Administration of a single dose of study drug will occur on Day 1. Following completion of all safety assessments and blood draws for PK analyses, subjects will be discharged on Day 3 or Day 4, depending on cohort.

Double-blind dosing will occur in cohorts 1 through 6. In these cohorts, 6 subjects will receive CT1812 and 2 will receive placebo. Doses will be escalated per protocol.

In cohort 1 only, 2 subjects (1 placebo/1 active CT1812) will be dosed 24 hours prior to the remaining subjects in the cohort. The remaining 6 subjects will be dosed if no safety concerns are identified in the first 2 subjects (the last 6 subjects will be admitted to the research unit one day later than the initial 2 subjects). In cohorts 2 through 7, all subjects will be enrolled and dosed together.

Following completion of each cohort, bioanalytical analyses for CT1812 PK will be performed and plasma Cmax concentrations will be reviewed. Enrollment of additional cohorts and dose escalations will not occur until safety assessments and PK analyses have been completed in the prior cohort.

The dose escalation plan may be adjusted in response to pharmacokinetic analyses, particularly if the relationship between dose and Cmax becomes non-proportional. If an MTD or a maximum allowable exposure is established at less than 650 mg (~8.45 mg/kg), fewer cohorts may be required, reducing the number of study subjects. Should an MTD not be identified (i.e. all doses are well tolerated and review of PK analyses reveal no clinical concerns), additional cohorts at higher doses may be enrolled. The maximum dose administered will not exceed 1350 mg (~18 mg/kg).

At the completion of dose escalation, one additional cohort of 6 subjects will be administered open-label CT1812 at the highest well-tolerated dose or potential therapeutic dose, 30 minutes following a standardized meal to test for food effects.

All subjects will be admitted to the clinical research unit on Day 0. Dosing will take place on the morning of Day 1. Blood draws for assessment of PK parameters will occur pre-dose and at 15, 30, 45, 60, and 90 minutes post dose as well as at 2, 3, 4, 8, 12, 24, 36 and 48 hours post dose. Subjects in cohorts 5 and 6 will have an additional sample drawn 72 hours after dosing. Subjects will be released on Day 3 or 4 following completion of all blood draws and safety assessments.

Part B - Multiple Ascending Dose in up to 60 Subjects

Following identification of the MTD in Part A and analysis of the pharmacokinetic data from Part A, the multiple ascending dose Part B will commence in 4 cohorts.

Screening procedures will occur on Days -21 to -3. Subjects will be admitted to the clinical research unit for 17 days. Once daily administration of study drug will be initiated at 25% of the MTD established in Part A. Dosing will occur on Days 1 - 14. Following completion of all safety assessments and blood draws for PK analyses, subjects will be discharged on Day 16.

In cohorts 3 and 4 only, subjects will undergo lumbar puncture and CSF sampling for CT1812 concentration analysis (single-point) at the steady state Tmax (time after dosing TBD).

In addition to cohorts 1-4, two cohorts of subjects aged 65 to 75 may be enrolled and dosed following identification of the multiple-dose MTD. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Impairment

• NCT number: NCT02570997
• Study type: Interventional
• Source: Cognition Therapeutics
• Status: Completed
• Phase: Phase 1
• Start date: September 2015