Japanese Phase 1 Multiple Ascending Dose 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-823778 in healthy Japanese subjects and Japanese patients with Type 2 Diabetes Mellitus.

Detailed Description
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MAD study - Multiple Ascending Dose study

Official Title
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A Randomized, Placebo-Controlled, Double-Blinded, Multiple Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-823778 in Healthy Subjects and Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: BMS-823778
* Drug: BMS-823778
* Drug: BMS-823778
* Drug: BMS-823778
* Drug: Placebo matching with BMS-823778


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese patients with Type 2 Diabetes Mellitus (T2DM) [Fasting glucose < 240 mg/dL, Hemoglobin A1c (HbA1c): 6.5% to 10.0% National Glycohemoglobin Standardization Program (NGSP)] who are treatment-naive and managed with diet and/or exercises only, ages: 20 to 65 years Exclusion Criteria: Patient who is taking any medication for T2DM Symptoms of poorly controlled diabetes that would preclude participation in this placebo-controlled trial Insulin therapy within one year of screening

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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: Panel 1: BMS-823778 or Placebo matching BMS-823778<br>Healthy Subjects | Drug: BMS-823778<br>* Capsules, Oral, 2 mg, Once daily, 14 days<br>Drug: Placebo matching with BMS-823778<br>* Capsules, Oral, 0 mg, Once daily, 14 days<br>|
| Experimental: Panel 2: BMS-823778 or Placebo matching BMS-823778<br>Healthy Subjects | Drug: BMS-823778<br>* Capsules, Oral, 12 mg, Once daily, 14 days<br>Drug: Placebo matching with BMS-823778<br>* Capsules, Oral, 0 mg, Once daily, 14 days<br>|
| Experimental: Panel 3: BMS-823778 or Placebo matching BMS-823778<br>Healthy Subjects | Drug: BMS-823778<br>* Capsules, Oral, 25 mg, Once daily, 14 days<br>Drug: Placebo matching with BMS-823778<br>* Capsules, Oral, 0 mg, Once daily, 14 days<br>|
| Experimental: Panel 4: BMS-823778 or Placebo matching BMS-823778<br>Subjects with T2DM | Drug: BMS-823778<br>* Capsules, Oral, 2 mg, Once daily, 14 days<br>Drug: Placebo matching with BMS-823778<br>* Capsules, Oral, 0 mg, Once daily, 14 days<br>|
| Experimental: Panel 5: BMS-823778 or Placebo matching BMS-823778<br>Subjects with T2DM | Drug: BMS-823778<br>* Capsules, Oral, 15 mg, Once daily, 14 days<br>Drug: Placebo matching with BMS-823778<br>* Capsules, 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, as measured by the number, frequency and intensity of adverse events, vital sign measurements, ECGs, physical examinations, and clinical laboratory tests |  | Up to Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Trough observed plasma concentration (Cmin) of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Time of maximum observed plasma concentration (Tmax) of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Area under the plasma concentration-time curve in one dosing interval [AUC(TAU)] of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Accumulation Index following multiple dosing (AI) of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Plasma half-life (T-HALF) of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Percent urinary recovery (% UR) of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Apparent total body clearance (CLT/F) of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Renal clearance from plasma (CLR) of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Peak to trough ratio (Cmax/Cmin) of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Effective plasma half-life (T-HALFeff) of BMS-823778, as measured by plasma/urine concentration |  | Up to Day 21 | 
| Pharmacodynamics, as measured by Serum concentration of cortisol and cortisone after an oral dose of cortisone and biomarkers for HPA axis activity (urinary free cortisol and cortisone, salivary cortisol, ACTH, DHEA-S and 4-androstenedione) | HPA = Hypothalamic-pituitary-adrenal DHEA-S = Dehydroepiandrosterone-sulphate ACTH = adrenocorticotropic hormone | Up to Day 21 |