Ascending Dose Study of CT1812 in Healthy Volunteers

NCT ID: NCT02570997

Last Updated: 2016-09-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30

Brief 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).

Detailed 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.

Conditions

Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

CT1812

In cohorts 1-6, 8 subjects will be enrolled. 6 subjects will receive CT1812. Doses will be escalated in the following sequence: 10mg, 30mg, 90mg, 180mg, 360mg, 650mg.

Should an MTD not be identified, additional cohorts at higher doses may be enrolled. The maximum dose administered will not exceed 1350mg.

Group Type: ACTIVE_COMPARATOR

CT1812

Intervention Type: DRUG

Doses will be escalated in the following sequence: 10mg, 30mg, 90mg, 180mg, 360mg, 650mg.

Matching Placebo

In cohorts 1-6, 8 subjects will be enrolled. 6 subjects will receive matching placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo administered.

Interventions

CT1812

Doses will be escalated in the following sequence: 10mg, 30mg, 90mg, 180mg, 360mg, 650mg.

Intervention Type: DRUG

Placebo

Matching placebo administered.

Intervention Type: DRUG

Other Intervention Names

Study drug

Eligibility Criteria

Inclusion Criteria

• Willing and able to provide written informed consent prior to initiation of any study-related procedures.
• Men and women either ≥ 18 and ≤ 55 years of age or ≥ 65 and ≤75 years of age, depending on cohort.
• In good health as determined by medical history, physical exam, laboratory examinations, ECG, and vital signs.
• BMI between 19 and 34 kg/m2, inclusive.
• Weight between 50 and 100 kg, inclusive.
• ECG without clinically significant pathologic abnormalities and with QTcB <450.
• Normotensive as defined by systolic BP ≤ 150 mmHg and diastolic BP ≤ 90 mmHg.
• Non-smokers.
• No suicidal ideation, as demonstrated by a score of "0" on the Columbia Suicide Severity Rating Scale (C-SSRS). Part B Only.
• Women who are neither pregnant (negative pregnancy test) nor nursing, and are either surgically sterile or postmenopausal.

Exclusion Criteria

• Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment that might increase the risk to the subject or confound interpretation of safety observations.
• Evidence of active infection requiring antibiotic therapy within 14 days prior to screening.
• Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
• History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin.
• Seropositive for human immunodeficiency virus (HIV).
• History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for Hepatitis B surface antigen [HbsAg] or anti-Hepatitis C [HCV] antibody).
• Clinically significant abnormalities in specified screening laboratory tests
• All prescription, over-the-counter and herbal medications are prohibited within 10 days prior to study dosing (with exception of calcium/vitamin D supplements, nasal steroids, ocular medications, and paracetamol at the discretion of the Investigator).
• Use of an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing in this study.
• Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs.
• Psychiatric history of current or past psychosis, bi-polar disorder, clinical depression, or anxiety disorder requiring chronic medication within the past 5 years.
• History of substance abuse.
• History of substance or drug dependence or positive urine drug screen at screening visit.
• History of head injury.
• Chronic kidney disease.
• Signs of dementia or cognitive impairment in the elder cohorts.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cognition Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jason Lickliter, MD

Role: PRINCIPAL_INVESTIGATOR

Nucleus Network Ltd

Locations

Nucleus Network Limited

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

Cog 0101

Identifier Type: -

Identifier Source: org_study_id