A Study of LY2409021 in Participants With Type 2 Diabetes Mellitus

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

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).

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Metformin; Drug: Placebo; Drug: LY2409021; Drug: Sitagliptin; Drug: Sulfonylurea

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11527
    • 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, Greece, 54636
    • 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.
• Puerto Rico
  • Hato Rey, Puerto Rico, 00917
    • PRADNET, Inc. Centro Especializado de Nutricion y Bariatria
  • San Juan, Puerto Rico, 00917-3104
    • American Telemedicine Center
  • San Juan, Puerto Rico, 909
    • GCM Medical Group PSC
• Taiwan
  • Changhua, Taiwan, 500
    • 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, Taiwan, 71004
    • 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.
• United States
  • California
    • Concord, California, United States, 94520
      • John Muir Health Network - The Osteoporosis Center
    • Fresno, California, United States, 93720
      • Valley Endocrine, Fresno
    • Los Angeles, California, United States, 90057
      • National Research Institute
  • Florida
    • Miami, Florida, United States, 33175
      • New Horizon Research Center
    • Miami, Florida, United States, 33135
      • Suncoast Research Group, LLC
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida, Inc.
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Medical Institute
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Diabetes and Osteoporosis Center
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar-Crosse Research Center
    • Crystal Lake, Illinois, United States, 60012
      • Midwest CRC
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Iderc, P.L.C.
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinic
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Centex Studies, Inc
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Cosmopolitan International Diabetes Center
    • Springfield, Missouri, United States, 65807
      • Mercy Medical Research Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center
  • New Jersey
    • Toms River, New Jersey, United States, 08753
      • SHS Clinical Research Group
  • Pennsylvania
    • Downingtown, Pennsylvania, United States, 19335
      • Office:Alwine,Lk
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • University Diabetes and Endocrine Consultants
  • Texas
    • Dallas, Texas, United States, 75251
      • Galenos Research
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Endocrine Center
    • Georgetown, Texas, United States, 78626
      • San Gabriel Clinical Research
    • San Antonio, Texas, United States, 78218
      • Oakwell Clinical Research
    • San Antonio, Texas, United States, 78240
      • Victorium Clinical Research
  • Washington
    • Seattle, Washington, United States, 98104
      • Polyclinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2409021; 20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Drug: Metformin; Administered orally; Drug: LY2409021; Administered orally; Drug: Sulfonylurea; Administered orally
Active Comparator: Sitagliptin; 100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Drug: Metformin; Administered orally; Drug: Sitagliptin; Administered orally; Drug: Sulfonylurea; Administered orally
Placebo Comparator: Placebo; Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Drug: Metformin; Administered orally; Drug: Placebo; Administered orally; Drug: Sulfonylurea; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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,
Population Pharmacokinetics: Apparent Volume of Distribution of LY2409021		Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,
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
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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Kazda CM, Frias J, Foga I, Cui X, Guzman CB, Garhyan P, Heilmann C, Yang JA, Hardy TA. Treatment with the glucagon receptor antagonist LY2409021 increases ambulatory blood pressure in patients with type 2 diabetes. Diabetes Obes Metab. 2017 Aug;19(8):1071-1077. doi: 10.1111/dom.12904. Epub 2017 Mar 27.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: April 8, 2014
• First Submitted That Met QC Criteria: April 8, 2014
• First Posted (Estimate): April 10, 2014

Study Record Updates

• Last Update Posted (Actual): October 9, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 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; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: 15286; I1R-MC-GLDJ (Other Identifier: Eli Lilly and Company); 2013-004275-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR