A Study to Evaluate BMS-986036 in Obese Adults With Type-2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to assess the potential of BMS-986036 for treatment obese adults with type-2 diabetes.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamic Effects of BMS-986036 in Obese Adults With Type-2 Diabetes

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Biological: BMS-986036
* Biological: Placebo (Matching with BMS-986036)


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Diagnosed with type-2 diabetes mellitus with HbA1c ≥6.5% to less than 10.0% Body mass index 30.0 to 50.0 Exclusion Criteria: Any significant acute or chronic medical illness Inability to self-administer subcutaneous injections Inability to be venipunctured Evidence of organ dysfunction beyond what is consistent with the target population History of allergy to PEGylated compounds or Fibroblast growth factor 21 (FGF21) related compounds
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 |
| --- | --- |
| Placebo Comparator: Treatment A: Placebo (Matching with BMS-986036 - Daily)<br>Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks | Biological: Placebo (Matching with BMS-986036)<br> <br> |
| Experimental: Arm 2: Treatment B: BMS-986036 (1 mg Daily)<br>BMS-986036 1 mg subcutaneous injection once daily for 12 weeks | Biological: BMS-986036<br> <br> |
| Experimental: Treatment C: BMS-986036 (5 mg Daily)<br>BMS-986036 5 mg subcutaneous injection once daily for 12 weeks | Biological: BMS-986036<br> <br> |
| Experimental: Treatment D: BMS-986036 (20 mg Daily)<br>BMS-986036 20 mg subcutaneous injection once daily for 12 weeks | Biological: BMS-986036<br> <br> |
| Experimental: Treatment E: BMS-986036 (20 mg Weekly)<br>BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks Followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks | Biological: BMS-986036<br> <br> Biological: Placebo (Matching with BMS-986036)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Week 12 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Percent Change in Glycosylated Hemoglobin A1c (HbA1c) from Baseline to Week 12 was reported. | Baseline (Day 1) and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight From Baseline to Week 12 | Change in Body Weight from Baseline to Week 12 as a part of Physical measurement was reported. | Baseline (Day 1) and Week 12 | 
| Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Composite Index of Insulin Sensitivity (CISI) (Matsuda Index) | Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG*FI)*(FPG+PG30*2+PG60*3+PG120*2)/8*(FPI+PI30*2+PI60*3+PI120*2)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60, and 120 minutes after oral glucose load; PI30,60,and 120=plasma insulin levels sampled at 30,60 and 120 minutes after the oral glucose load. | Baseline (Day 1) and Week 12 | 
| Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | Homeostasis model assessment of insulin resistance (HOMA-IR) was used as a validated measure of insulin resistance. HOMA-IR is calculated using the following formula's fasting glucose(mg/dL) x fasting insulin(mU/L) / 405. | Baseline (Day 1) and Week 12 | 
| Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Quantitative Insulin Sensitivity Check Index (QUICKI) | The Quantitative Insulin Sensitivity Check Index (QUICKI) score, measures insulin sensitivity which is the inverse of insulin resistance. QUICKI is derived using the inverse of the sum of the logarithms of the fasting insulin and fasting glucose: 1 / (log(fasting insulin mU/L) + log(fasting glucose mg/dL)). | Baseline (Day 1) and Week 12 | 
| Change in Oral Glucose Tolerance Test (OGTT) Area Under the Curve From 0 to 2 Hours for Postprandial Glucose From Baseline to Week 12 | Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. Plasma Glucose levels over 2 hours were shown as Area Under the Curve, (AUC). | Baseline (Day 1) and Week 12 | 
| Change in OGTT Insulin AUC (0-2 Hours) From Baseline to Week 12 | Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. Insulin levels over 2 hours were shown as Area Under the Curve, (AUC). | Bseline (Day 1) and Week 12 | 
| Change in OGTT C-peptide AUC (0-2 Hours) From Baseline to Week 12 | Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. C-peptide levels over 2 hours were shown as Area Under the Curve, (AUC). | Baseline (Day 1) and Week 12 | 
| Average Concentration (Cavg) of C-terminal Intact BMS-986036 | Cavg of C-terminal Intact BMS-986036 was reported. | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | 
| Maximum Observed Concentration (Cmax) of C-terminal Intact BMS-986036 | Maximum observed concentration (Cmax) of C-terminal Intact BMS-986036 was reported. | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | 
| Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) of C-terminal Intact BMS-986036 | AUC [0-24 hours, ss] of C-terminal Intact BMS-986036 was reported. | Pre-dose, 6, 24 hours postdose on Week 8 | 
| Area Under the Concentration-time Curve From Time Zero to 168 Hours at Steady State (AUC [0-168 Hours, ss]) of C-terminal Intact BMS-986036 | AUC [0-168 hours, ss] of C-terminal Intact BMS-986036 was reported. | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | 
| Average Concentration (Cavg) of Total BMS-986036 | Cavg of Total BMS-986036 was reported. | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | 
| Maximum Observed Concentration (Cmax) of Total BMS-986036 | Maximum observed concentration (Cmax) of Total BMS-986036 was reported. | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | 
| Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) Total BMS-986036 | AUC [0-24 hours, ss] of Total BMS-986036 was reported. | Pre-dose, 6, 24 hours postdose on Week 8 | 
| Area Under the Concentration-time Curve From Time Zero to 168 Hours at Steady State (AUC [0-168 Hours, ss]) of Total BMS-986036 | AUC [0-168 hours, ss] of Total BMS- 986036 was reported. | Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126) | 
| Percentage of Participants With ANTI-BMS-986036 Antibody Response | Percentage of Participants with ANTI-BMS-986036 Antibody Response (ADA positive and ADA Negative) was reported. Participants were monitored for antibodies to BMS-986036 with an anti-BMS-986036 antibody assay. Titers were reported for samples testing positive in an assay. | Baseline and Day 126 |