A Study of LY2409021 in Participants With Type 2 Diabetes Mellitus

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Phase 2, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of LY2409021 Compared to Sitagliptin in Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02111096
• Other study ID #: 15286
• Secondary ID: I1R-MC-GLDJ2013-
• Status: Terminated
• Phase: Phase 2
• Start date: April 2014
• Est. completion date: September 2015

Study information

• Verified date: September 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The intent of this study is to assess the safety of LY2409021 in participants with Type 2 diabetes mellitus taking metformin and sulfonylurea as prescribed by their personal physician. The study treatment is expected to last 12 months (52 weeks).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 174
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• Have been treated with a stable dose of metformin for at least 3 months and have been treated with an optimally effective and stable dose of an sulfonylurea for at least 6 months prior to screening.

• HbA1c value between 7.0% and 10.0%, inclusive.

• Body mass index (BMI) between 20 and 45 kilograms/square meter (kg/m^2), inclusive.

Exclusion Criteria:

• Known type 1 diabetes mellitus.

• More than 1 episode of severe hypoglycemia within 6 months prior to screening.

• Two or more emergency room visits or hospitalizations due to poor glucose control in the 6 months prior to screening.

• Severe gastrointestinal disease that may significantly impact gastric emptying or motility or having undergone gastric bypass or gastric banding surgery.

• Previous history or active diagnosis of pancreatitis.

• Positive hepatitis B surface antigen or hepatitis C antibody.

• Clinical signs or symptoms of liver disease, or hepatic aminotransferases (aminotransferase or alanine aminotransferase) greater than 2.0× upper limit of normal (ULN) or elevated alkaline phosphatase (greater than ULN) unrelated to bone metabolic disease.

• Elevated total bilirubin level (greater than ULN), clinically suspicious signs/symptoms of cirrhosis or history of cirrhosis.

• Current diagnosis, personal history of neuroendocrine tumors, family history of any type of multiple endocrine neoplasia (MEN), or Von Hippel-Lindau.

• Contraindications for magnetic resonance imaging.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• LY2409021
Administered orally
• Sitagliptin
Administered orally
• Placebo
Administered orally
• Metformin
Administered orally
• Sulfonylurea
Administered orally

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.	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
Puerto Rico	PRADNET, Inc. Centro Especializado de Nutricion y Bariatria	Hato Rey
Puerto Rico	American Telemedicine Center	San Juan
Puerto Rico	GCM Medical Group PSC	San Juan
Taiwan	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.	Changhua
Taiwan	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.	Yong Kung City
United States	University Diabetes and Endocrine Consultants	Chattanooga	Tennessee
United States	Cedar-Crosse Research Center	Chicago	Illinois
United States	Cosmopolitan International Diabetes Center	Columbia	Missouri
United States	John Muir Health Network - The Osteoporosis Center	Concord	California
United States	Midwest CRC	Crystal Lake	Illinois
United States	Dallas Diabetes Endocrine Center	Dallas	Texas
United States	Galenos Research	Dallas	Texas
United States	Iderc, P.L.C.	Des Moines	Iowa
United States	Office:Alwine,Lk	Downingtown	Pennsylvania
United States	Valley Endocrine, Fresno	Fresno	California
United States	San Gabriel Clinical Research	Georgetown	Texas
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	Centex Studies, Inc	Lake Charles	Louisiana
United States	Palm Research Center	Las Vegas	Nevada
United States	National Research Institute	Los Angeles	California
United States	New Horizon Research Center	Miami	Florida
United States	Suncoast Research Group, LLC	Miami	Florida
United States	Oakwell Clinical Research	San Antonio	Texas
United States	Victorium Clinical Research	San Antonio	Texas
United States	Polyclinic	Seattle	Washington
United States	Mercy Medical Research Institute	Springfield	Missouri
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	SHS Clinical Research Group	Toms River	New Jersey
United States	Cotton O'Neil Clinic	Topeka	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Greece,  Puerto Rico,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to 6 Months in Hepatic Fat Fraction	The hepatic fat fraction (HFF) was calculated by a core imaging laboratory from noncontrast magnetic resonance imaging (MRI) of the liver. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.	Baseline, 6 months
Secondary	Change From Baseline to 6 Months in Alanine Aminotransferase Levels	Alanine aminotransferase (ALT) assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.	Baseline, 6 months
Secondary	Number of Participants With Hepatobiliary Adverse Events of Special Interest (AESI)	Number of participants with ALT or AST greater than 3 times the upper limit of normal at a post-baseline visit. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.	Baseline, 6 months
Secondary	Change From Baseline to 6 Months in Fasting Lipids Levels	Lipid values (cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides) assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.	Baseline, 6 months
Secondary	Change From Baseline to 6 Months in Fasting Blood Glucagon	Glucagon values assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.	Baseline, 6 months
Secondary	Change From Baseline to 6 Months in Body Weight	Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.	Baseline, 6 months
Secondary	Change From Baseline to 6 Months in Hemoglobin A1c (HbA1c)	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, visit, baseline score, and treatment-by-visit.	Baseline, 6 months
Secondary	Change From Baseline to 6 Months in Fasting Plasma Glucose	Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.	Baseline, 6 months
Secondary	Change From Baseline to 6 Months in Blood Pressure	Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured in triplicate throughout the study. At each visit, all available blood pressure measurements for a subject were averaged to provide the blood pressure for that visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.	Baseline, 6 months
Secondary	Change From Baseline to 6 Months in Pulse Rate	Seated pulse rate was measured in triplicate throughout the study. At each visit, all available pulse measurements for a subject were averaged to provide the pulse for that visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.	Baseline, 6 months
Secondary	Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG)	7-point profile consists of pre-meal and 2-hour postprandial SMBG measurements for the morning, midday, and evening meals in 1 day and at 3 AM (nocturnal blood glucose measurement). Pre-meal measurements were taken before the subject began eating the meal. Participants recorded their glucose measurements in their study diaries.	Baseline, 6 months
Secondary	Population Pharmacokinetics: Apparent Clearance of LY2409021	Reported as a Population Estimate with % Standard Errors of Estimation (SEE), 5th-95th confidence interval.	Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,
Secondary	Population Pharmacokinetics: Apparent Volume of Distribution of LY2409021		Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,
Secondary	Rate of Hypoglycemic Events Adjusted Per 30 Days	Documented symptomatic hypoglycemia, an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration <=70 mg/dL (<=39 mmol/L),is presented. Rate: (30 days) is calculated as: (number of episodes during the time period divided by the number of days during the time period) multiplied by 30.	Baseline through 6 months
Secondary	Number of Participants With Hypoglycemic Events	Documented symptomatic hypoglycemia, an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration <=70 mg/dL (<=39 mmol/L), is presented. The number of subjects with an event are subjects who had at least one episode of documented symptomatic hypoglycemia during the time period.	Baseline through 6 months