A Study to Compare a New Drug for Type 2 Diabetes to Placebo and to a Treatment Already Available for Type 2 Diabetes

Phase 2CompletedNCT02119819

OPKO Health, Inc.420 enrolled

Overview

The main purpose of this study is to compare the safety and effectiveness of the study drug known as LY2944876 to exenatide extended-release and placebo in participants with type 2 diabetes mellitus. All drugs will be given by an injection under the skin. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry. Participants' involvement in the study is expected to last about 30 weeks.

The study will include a 12 week blinded treatment period, where neither the participant nor the investigator will know to which treatment each individual is assigned. Thereafter follows a 12 week period where participants and the investigator will know which treatment they are assigned to. Participants' on LY2944876 and on exenatide extended-release continue treatment in this period, those who received placebo will be followed without treatment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

420

Conditions

Diabetes Mellitus, Type 2

Interventions

LY2944876DRUG

Administered SC

Exenatide extended-releaseDRUG

Administered SC

PlaceboDRUG

Administered SC

Metformin

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Men or women with diabetes mellitus Type 2 * Have screening HbA1c ≥7.0% and ≤10.5% either on diet and exercise alone or on a stable dose of metformin (≥1000 mg/day) for 3 months prior to screening * Have body mass index (BMI) ≥23 and ≤45 kilograms per meter squared at screening Exclusion Criteria: * Women of child bearing potential * Participants who have used thiazolidinediones within 3 months prior to screening, or any other drugs for treatment of hyperglycemia (except metformin) within the prior 2 months * Participants who have used insulin for diabetic control for more than 6 consecutive days within the prior year * Participants with impaired renal function (serum creatinine \>124 micromole per liter (µmol/L) \[1.4 milligrams per deciliter (mg/dL)\] in women, \>133 µmol/L \[1.5 mg/dL\] in men)

Locations (51)

Outcomes

Primary Outcomes

Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Time frame: Baseline, Week 12

Secondary Outcomes

Change From Baseline in HbA1c at Week 24

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Time frame: Baseline, Week 24

Percent Change From Baseline in Body Weight

Time frame: Baseline, Week 12; Baseline, Week 24

Change From Baseline in Fasting Blood Glucose

Least square means (LSM) was calculated from mixed-effects model with repeated measures (MMRM) analysis using restricted maximum likelihood (REML) with metformin use, baseline body mass index (BMI) category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect.

Time frame: Baseline, Week 12; Baseline, Week 24

Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values

SMBG 7-point profiles were measured at morning pre-meal, morning 2 hours post-meal, mid-day pre-meal, mid-day 2 hours post-meal, evening pre-meal, evening 2 hours post-meal, and at bedtime. LSM were calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect.

Time frame: Baseline, Week (Wk) 12; Baseline, Week 24

Change From Baseline in Lipids

Data from ClinicalTrials.gov

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John Muir Physician Network Clinical Research Center

Concord, California, United States

Valley Endocrine, Fresno

Fresno, California, United States

National Research Institute

Los Angeles, California, United States

Desert Medical Group Inc

Palm Springs, California, United States

Artemis Institute for Clinical Research

San Diego, California, United States

Encompass Clinical Research

Spring Valley, California, United States

Meridien Research

Bradenton, Florida, United States

M & O Clinical Research, LLC

Fort Lauderdale, Florida, United States

Suncoast Research Group, LLC

Miami, Florida, United States

Suncoast Clinical Research

New Port Richey, Florida, United States

...and 41 more locations

Change from baseline in high-density lipoprotein cholesterol (HDL-C), total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C). LSM was calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant an a random effect.

Time frame: Baseline, Week 24

Change From Baseline in Fasting Fibroblast Growth Factor 21

LSM was calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.

Time frame: Baseline, Week 12; Baseline, Week 24

Percentage of Participants Requiring Rescue Therapy

Participants who received rescue medication with non-study antihyperglycemic medications or change their stable dose of metformin.

Time frame: Baseline through Therapy Completion (Week 24)

Percentage of Participants Developing Anti-Drug Antibodies to LY2944876

Percentage of participants developing anti-drug antibodies to LY2944876.

Time frame: Week 12 and Week 24

Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876

Evaluable pharmacokinetic concentrations from the specified timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.

Time frame: Baseline, Week 8, Week 12, Week 16, Week 20, Week 24

Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876

Time frame: Baseline, Week 8, Week 12, Week 16, Week 20, Week 24

Change From Baseline in Adiponectin Levels

LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.

Time frame: Baseline, Week 12; Baseline, Week 24

Change From Baseline in Beta-Hydroxy Butyrate Levels

Time frame: Baseline, Week 12; Baseline, Week 24

Change From Baseline in Glucagon Levels

Time frame: Baseline, Week 12; Baseline, Week 24

Change From Baseline in Insulin Levels

Time frame: Baseline, Week 12; Baseline, Week 24