Japanese Phase 1 Multiple Ascending Dose (MAD) Study

Study Overview
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Brief Summary
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The purpose of this clinical study is to assess the safety and tolerability of multiple oral doses of BMS-820836 in healthy Japanese subjects and Japanese patients with depression.

Official Title
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Randomized, Placebo-Controlled, Double-Blind, Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-820836 in Healthy Japanese Subjects and Japanese Patients With Depression

Conditions
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Depression

Intervention / Treatment
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* Drug: BMS-820836
* Drug: BMS-820836
* Drug: BMS-820836
* Drug: Placebo matching BMS-820836
* Drug: BMS-820836


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese subjects and Japanese patients with depression (Hamilton Rating Scale for Depression (HAM-D) ≥ 14), ages 20 to 55 years. Exclusion Criteria: Any significant acute or chronic medical illness. Non-compliance, or overall not suitable as determined by the investigator. History of, or current clinically significant psychiatric disorders or illnesses, substance abuse or dependence.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm1: BMS-820836<br>Panels 1-4 are fixed dose panels (0.5, 1, 1 and 2 mg respectively), Panels 5-7 are titration dose panels (initiated at 1 mg and dose escalated to the target dose of 2 mg) | Drug: BMS-820836<br>* Tablets, Oral, 0.5 mg, Once daily, 14 days<br>Drug: BMS-820836<br>* Tablets, Oral, 1 mg, Once daily, 14 days<br>Drug: BMS-820836<br>* Tablets, Oral, 2 mg, Once daily, 14 days<br>Drug: BMS-820836<br>* Tablets, Oral, (initiated at 1 mg and dose escalated to the target dose of 2 mg), Once daily, 14 days<br>|
| Placebo Comparator: Arm 2: Placebo matching BMS-820836<br>Panels 1-4 are fixed dose panels (0.5, 1, 1 and 2 mg respectively), Panels 5-7 are titration dose panels (initiated at 1 mg and dose escalated to the target dose of 2 mg) | Drug: Placebo matching BMS-820836<br>* Tablets, Oral, 0 mg, Once daily, 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability based on medical review of adverse events & results of vital sign measurements, electrocardiogram (ECGs), physical examinations, clinical laboratory test, suicidality evaluation & Montgomery Asberg Depression Rating Scale (MADRS) |  | Day 1 through Day 33 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple-dose pharmacokinetics parameter Maximum observed concentration (Cmax) of BMS-820836 and BMS-821007 |  | Day1 through Day 33 | 
| Multiple-dose pharmacokinetics parameter Concentration at 24 h (C24) of BMS-820836 and BMS-821007 |  | Day1 through Day 33 | 
| Multiple-dose pharmacokinetics parameter Time of maximum observed concentration (Tmax) of BMS-820836 and BMS-821007 |  | Day1 through Day 33 | 
| Multiple-dose pharmacokinetics parameter Area under the concentration-time curve in one dosing interval (AUC(TAU)) of BMS-820836 and BMS-821007 |  | Day1 through Day 33 | 
| Multiple-dose pharmacokinetics parameter Apparent total body clearance (CLT/F) of BMS-820836 and BMS-821007 |  | Day1 through Day 33 | 
| Multiple-dose pharmacokinetics parameter accumulation index (AI) of BMS-820836 and BMS-821007 |  | Day1 through Day 33 | 
| Multiple-dose pharmacokinetics parameter half-life (T-HALF) of BMS-820836 and BMS-821007 |  | Day1 through Day 33 | 
| Multiple-dose pharmacokinetics parameter Molar ratio of metabolite to parent Cmax or AUC(TAU) |  | Day1 through Day 33 | 
| ECG parameters (heart rate, PR, QRS, QT, and QTcF intervals) | QTcF intervals - QT interval corrected for heart rate according to Fridericia's formula | Day1 through Day 33 | 
| Vital sign measures (heart rate and blood pressure) and the orthostatic changes |  | Day1 through Day 33 |