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

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

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

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 2
• Intervention / Treatment: Biological: Placebo (Matching with BMS-986036); Biological: BMS-986036

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G3K 2P8
    • Alpha-Recherche Clinique
  • British Columbia
    • Vancouver, British Columbia, Canada, V6J 1S3
      • Manna Research Vancouver
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal And Associates
  • Quebec
    • Drummondville, Quebec, Canada, J2B 7T1
      • Rhodin Recherche Clinique
    • Montreal, Quebec, Canada, H1M 1B1
      • Recherche GCP Research
    • Victoriaville, Quebec, Canada, G6P 6P6
      • Medexa Recherche
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Clinical Research
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials Llc
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
    • Spring Valley, California, United States, 91978-1522
      • Encompass Clinical Research
  • Florida
    • Cooper City, Florida, United States, 33024
      • ALL Medical Research, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates, Inc.
  • New Jersey
    • Trenton, New Jersey, United States, 08611
      • Premier Research
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Metrolina Internal Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Grp, Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Treatment A: Placebo (Matching with BMS-986036 - Daily); Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks	Biological: Placebo (Matching with BMS-986036)
Experimental: Arm 2: Treatment B: BMS-986036 (1 mg Daily); BMS-986036 1 mg subcutaneous injection once daily for 12 weeks	Biological: BMS-986036
Experimental: Treatment C: BMS-986036 (5 mg Daily); BMS-986036 5 mg subcutaneous injection once daily for 12 weeks	Biological: BMS-986036
Experimental: Treatment D: BMS-986036 (20 mg Daily); BMS-986036 20 mg subcutaneous injection once daily for 12 weeks	Biological: BMS-986036
Experimental: Treatment E: BMS-986036 (20 mg Weekly); 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: Placebo (Matching with BMS-986036); Biological: BMS-986036

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Charles ED, Neuschwander-Tetri BA, Pablo Frias J, Kundu S, Luo Y, Tirucherai GS, Christian R. Pegbelfermin (BMS-986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study. Obesity (Silver Spring). 2019 Jan;27(1):41-49. doi: 10.1002/oby.22344. Epub 2018 Dec 6.

Helpful Links

• BMS clinical trial educational resource
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2014
• Primary Completion (Actual): September 22, 2015
• Study Completion (Actual): May 17, 2016

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: March 24, 2014
• First Posted (Estimate): March 27, 2014

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 29, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: MB130-002