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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Comparison of the Oxyntomodulin Analog, LY2944876, to Once-Weekly Exenatide and to Placebo in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02119819
• Other study ID #: 15062
• Secondary ID: 2013-003552-21I7
• Status: Completed
• Phase: Phase 2
• Start date: April 2014
• Est. completion date: October 2015

Study information

• Verified date: May 2021
• Source: OPKO Health, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: October 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• LY2944876
Administered SC
• Exenatide extended-release
Administered SC
• Placebo
Administered SC
• Metformin
Oral

Locations

Country	Name	City	State
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ampelokipoi
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Athens
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Thessaloniki
Mexico	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chihuahua
Mexico	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Guadalajara
Mexico	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tampico
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bialystok
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gdansk
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gdynia
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lodz
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Poznan
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Szczecin
Poland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Warsaw
Puerto Rico	Manati Medical Center	Manati
Puerto Rico	American Telemedicine Center	San Juan
Romania	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cluj-Napoca
Romania	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Iasi
Romania	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ploiesti
Romania	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Targu Mures
Romania	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Timisoara
United States	Blair Medical Associates, Inc.	Altoona	Pennsylvania
United States	Texas Diabetes and Endocrinology	Austin	Texas
United States	Wade Family Medicine	Bountiful	Utah
United States	Meridien Research	Bradenton	Florida
United States	John Muir Physician Network Clinical Research Center	Concord	California
United States	The Corvallis Clinic P.C.	Corvallis	Oregon
United States	Dallas Diabetes Endocrine Center	Dallas	Texas
United States	Iderc, P.L.C.	Des Moines	Iowa
United States	Lillestol Research LLC	Fargo	North Dakota
United States	M & O Clinical Research, LLC	Fort Lauderdale	Florida
United States	Valley Endocrine, Fresno	Fresno	California
United States	San Gabriel Clinical Research	Georgetown	Texas
United States	High Point Clinical Trials Center	High Point	North Carolina
United States	East West Medical Institute	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho
United States	National Research Institute	Los Angeles	California
United States	Suncoast Research Group, LLC	Miami	Florida
United States	Southern New Hampshire Diabetes and Endocrinology	Nashua	New Hampshire
United States	Suncoast Clinical Research	New Port Richey	Florida
United States	Compass Research	Oviedo	Florida
United States	Desert Medical Group Inc	Palm Springs	California
United States	St John's Mercy Medical Center	Saint Louis	Missouri
United States	Oakwell Clinical Research	San Antonio	Texas
United States	Artemis Institute for Clinical Research	San Diego	California
United States	Encompass Clinical Research	Spring Valley	California
United States	Mercy Medical Research Institute	Springfield	Missouri
United States	Southwest Health Associates, P.A.	Sugar Land	Texas
United States	Cotton O'Neil Diabetes and Endocrinology Center	Topeka	Kansas
United States	Mercy Health Research	Washington	Missouri
United States	Clinical Research of Central Florida	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
OPKO Health, Inc.

Countries where clinical trial is conducted

United States,  Greece,  Mexico,  Poland,  Puerto Rico,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Week 12
Secondary	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.	Baseline, Week 24
Secondary	Percent Change From Baseline in Body Weight		Baseline, Week 12; Baseline, Week 24
Secondary	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.	Baseline, Week 12; Baseline, Week 24
Secondary	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.	Baseline, Week (Wk) 12; Baseline, Week 24
Secondary	Change From Baseline in Lipids	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.	Baseline, Week 24
Secondary	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.	Baseline, Week 12; Baseline, Week 24
Secondary	Percentage of Participants Requiring Rescue Therapy	Participants who received rescue medication with non-study antihyperglycemic medications or change their stable dose of metformin.	Baseline through Therapy Completion (Week 24)
Secondary	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Percentage of participants developing anti-drug antibodies to LY2944876.	Week 12 and Week 24
Secondary	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.	Baseline, Week 8, Week 12, Week 16, Week 20, Week 24
Secondary	Pharmacokinetics: Area Under the Concentration Curve (AUC) 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.	Baseline, Week 8, Week 12, Week 16, Week 20, Week 24
Secondary	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.	Baseline, Week 12; Baseline, Week 24
Secondary	Change From Baseline in Beta-Hydroxy Butyrate 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.	Baseline, Week 12; Baseline, Week 24
Secondary	Change From Baseline in Glucagon 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.	Baseline, Week 12; Baseline, Week 24
Secondary	Change From Baseline in Insulin 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.	Baseline, Week 12; Baseline, Week 24