Multiple Ascending Dose Study of BMS-820132 in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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BMS-820132 is an investigational new drug being developed by BMS for treating Type 2 diabetes. The purpose of this study is to test the safety/tolerability (potential side effects) of multiple doses of the investigational new drug, as well as the amount of study drug in the blood and its effects on blood sugar,in subjects with type 2 diabetes.

Detailed Description
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Study Classification: Safety, Pharmacokinetics/dynamics

Official Title
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Placebo-Controlled, Ascending Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-820132 in Subjects With Type 2 Diabetes Treated With Metformin Monotherapy.

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Placebo
* Drug: Placebo
* Drug: BMS-820132
* Drug: BMS-820132
* Drug: BMS-820132
* Drug: BMS-820132
* Drug: BMS-820132
* Drug: BMS-820132
* Drug: BMS-820132


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females of childbearing potential (willing to use an acceptable method of contraception), or females of non-childbearing potential (i.e., post-menopausal or surgically sterile). Diagnosis of type 2 diabetes treated with metformin monotherapy (at least 1500 mg/day for at least 6 months) on a stable regimen for at least 2 months. Body Mass Index (BMI) of 18.5 to 40 kg/m2. Fasting glucose in the range of 125-275 mg/dL. Hemoglobin A1c (HbA1c) in the range of 7.0% -11.0%. Fasting C-peptide > 1 ng/mL. Exclusion Criteria: Clinically significant deviation from normal in medical history, physical examination, electrocardiograms (ECGs), and clinical laboratory determinations, and any significant acute or chronic medical illness other than stable and well controlled hypertension, microalbuminuria, dyslipidemia, depression, or hypothyroidism. History of diabetic ketoacidosis, hyperosmolar nonketotic syndrome, lactic acidosis, hypoglycemia (i.e., ≥ 1 self-reported episodes of hypoglycemia within the last 3 months or ≥ 2 self-reported episodes of hypoglycemia within the last 6 months), or hypoglycemia unawareness. Any major surgery within 4 weeks of study drug administration. Any gastrointestinal surgery that could impact upon the absorption of study drug. Smoking more than 10 cigarettes per day. Recent drug or alcohol abuse. Women who are pregnant or breastfeeding. Positive urine screen for drugs of abuse. Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or Human Immunodeficiency Virus (HIV)-1, -2 antibody.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 BMS-820132 or placebo<br> | Drug: Placebo<br>* capsule, Oral, 0.0mg, twice daily, 14 day<br>Drug: BMS-820132<br>* Capsule, Oral, 15mg, twice daily, 14 day<br>|
| Active Comparator: Arm 2 BMS-820132 or placebo<br> | Drug: Placebo<br>* capsule, Oral, 0.0mg, twice daily, 14 day<br>Drug: BMS-820132<br>* Capsule, Oral, 60mg, twice daily, 14 day<br>|
| Active Comparator: Arm 3 BMS-820132 or placebo<br> | Drug: Placebo<br>* capsule, Oral, 0.0mg, twice daily, 14 day<br>Drug: BMS-820132<br>* Capsule, oral, 150mg, twice daily, 14 day<br>|
| Active Comparator: Arm 4 BMS-820132 or placebo<br> | Drug: Placebo<br>* capsule, Oral, 0.0mg, twice daily, 14 day<br>Drug: BMS-820132<br>* Capsule, Oral, 300mg, twice daily, 14 day<br>|
| Active Comparator: Arm 5 BMS-820132 or placebo<br> | Drug: Placebo<br>* capsule, Oral, 0.0mg, twice daily, 14 day<br>Drug: BMS-820132<br>* Capsule, Oral, 450mg, twice daily, 14 day<br>|
| Active Comparator: Arm 6 BMS-820132 or placebo<br> | Drug: Placebo<br>* Capsule, Oral, 0.0mg, once daily, 14 day<br>Drug: BMS-820132<br>* Capsule, Oral, To be determined (TBD), once daily, 14 day<br>|
| Active Comparator: Arm 7 BMS-820132 or placebo<br> | Drug: Placebo<br>* Capsule, Oral, 0.0mg, once daily, 14 day<br>Drug: BMS-820132<br>* Capsule, Oral, To be determined (TBD), once daily, 14 day<br>|
| Active Comparator: Arm 8 BMS-820132 or placebo<br> | Drug: Placebo<br>* Capsule, Oral, 0.0mg, once daily, 14 day<br>Drug: BMS-820132<br>* Capsule, Oral, To be determined (TBD), once daily, 14 day<br>|
| Active Comparator: Arm 9 BMS-820132 or placebo<br> | Drug: Placebo<br>* capsule, Oral, 0.0mg, twice daily, 14 day<br>Drug: BMS-820132<br>* Capsule, Oral, 5 mg, twice daily, 14 day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, physical examinations, clinical laboratory determinations, electrocardiograms (ECG), and vital sign assessments. |  | Throughout the study drug administration period (14 days) | 
| Adverse events, physical examinations, clinical laboratory determinations, electrocardiograms (ECG), and vital sign assessments. |  | within 7 days after the final dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of BMS-820132 |  | Day 1 and Day 14 | 
| Time of maximum observed plasma concentration (Tmax) of BMS-820132 |  | Day 1 and Day 14 | 
| Trough observed plasma concentration (Cmin) of BMS-820132 |  | Day 1 through Day 14 (selected days) | 
| Area under the plasma concentration-time curve over one dosing interval [AUC(TAU)] of BMS-820132 |  | Day 1 and Day 14 | 
| Accumulation index (AI) of BMS-820132 |  | Day 14 | 
| Half life (T-Half) of BMS-820132 |  | Day 14 | 
| AUC(0-24 h) and postprandial AUC(0-4h) for biomarkers of glucose homeostasis |  | Day -1, Day 1, Day 7 and Day 14 |