A Study of LY2189102 in Patients With Type 2 Diabetes

Phase 2 Randomized, Double-blind, Placebo Controlled, Parallel Design Study in Patients With Type 2 Diabetes Mellitus Who Are Stable on Diet and Exercise, With or Without Metformin Monotherapy.

Study to evaluate the safety, tolerability and efficacy of LY2189102 in patients with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: LY2189102; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36689
      • 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.
  • California
    • Anaheim, California, United States, 92801
      • 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.
    • Chula Vista, California, United States, 91911
      • 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.
    • La Mesa, California, United States, 91942
      • 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.
    • Walnut Creek, California, United States, 94598
      • 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.
  • District of Columbia
    • Washington, District of Columbia, United States, 20003
      • 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.
  • Florida
    • Miami, Florida, United States, 33169
      • 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.
    • Miami Gardens, Florida, United States, 33169
      • 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.
  • Idaho
    • Boise, Idaho, United States, 83702
      • 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.
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • 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.
  • Michigan
    • Dearborn, Michigan, United States, 48126
      • 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.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • 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.
  • Texas
    • Arlington, Texas, United States, 76014
      • 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.
    • Dallas, Texas, United States, 75230
      • 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.
    • San Antonio, Texas, United States, 78229
      • 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.
    • Tomball, Texas, United States, 77375
      • 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.
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • 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.
  • Virginia
    • Richmond, Virginia, United States, 23294
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have Type 2 Diabetes and confirmed by fasting C-peptide levels greater than or equal to 0.8 nanograms per milliliter [ng/ml]), with duration of more than 3 months.
• Body mass index between 25 and 40 kilograms per square meter (kg/m2).
• Stable on diet and exercise alone, with or without metformin monotherapy (stable regimen or dose for at least 8 weeks).
• Drug-naïve or previous anti-diabetic pharmacotherapy use is allowed (for the latter, patient must have stopped taking pharmacotherapy greater than 12 weeks prior to screening and only if deemed appropriate by the investigator).
• Angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, thiazide diuretics or calcium channel blockers are permitted for the treatment of hypertension or proteinuria.
• Glycated hemoglobin level between 7% and 10%.
• Baseline High-sensitivity C-reactive protein greater than or equal to 2 milligrams per liter (mg/L)
• Females of childbearing potential (not surgically sterilized and between menarche and 1 year post-menopause) must test negative for pregnancy at the time of enrollment based on a pregnancy test. Furthermore, sexually active female and male participants must agree to use 2 reliable methods of birth control during the study and for 3 months following the last dose of study drug.
• Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.

Exclusion Criteria:

• Current use of anti-diabetic pharmacotherapy (except metformin, under conditions specified in Inclusion Criteria above).
• Current treatment with anti-inflammatory drugs, including corticosteroids and non-steroidal anti-inflammatory drugs (100 mg per day or less of aspirin allowed).
• Within 60 days of the initial dose of the study drug, have received treatment with a drug that has not received regulatory approval for any indication.
• Presence of autoantibodies to glutamic acid decarboxylase 65 or islet-cell autoantibody-2.
• Evidence of tuberculosis as documented by a specific assay, medical history, and chest x-ray. A specific assay, (for example, tuberculin testing) will be conducted unless it is medically inappropriate. Exceptions include patients with a history of a positive specific assay for TB who have been treated with isonicotinyl hydrazine (documented) for at least 6 months, or patients with a previous diagnosis of TB who have been appropriately treated and can provide documentation.
• Symptomatic herpes zoster within 3 months of randomization.
• Show evidence of hepatitis C and/or positive hepatitis B surface antigen.
• Show evidence of human immunodeficiency virus and/or positive test of antibodies to human immunodeficiency virus (HIV).
• Received live or attenuated vaccine(s) within the previous 3 months prior to randomization or will receive within 3 months from the end of study.
• Screening serum creatinine greater than 2.0 milligrams per deciliter (mg/dL).
• Serum aspartate aminotransferase or alanine aminotransaminase concentration greater than 2x the upper limit of normal.
• Known allergies to LY2189102 or excipients.
• Previously completed or withdrawn from this study or any other study investigating LY2189102.
• Have donated blood of greater than 500 mL within the preceding 30 days and intend to donate within 3 months from the end of study.
• Have had other recent or ongoing signs of infection (for example, fever, current treatment with antibiotics).
• Experienced a serious bacterial infection within 6 months of randomization.
• Have a serious medical illness including but not limited to any cardiovascular, hepatic, respiratory, hematological, endocrine, or neurological disease, or any clinically significant laboratory abnormality.
• Have had lymphoma, leukemia, or any non-breast malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease.
• Have had a previous reaction to other biologics that, in the opinion of the investigator, puts the patient at serious risk.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.6 milligrams (mg) LY2189102	Drug: LY2189102; Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.
Experimental: 18 mg LY2189102	Drug: LY2189102; Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.
Experimental: 180 mg LY2189102	Drug: LY2189102; Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.
Placebo Comparator: Placebo; 0.9% Sodium Chloride	Drug: Placebo; Participants received 2 SC injections weekly for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Glycosylated Hemoglobin (HbA1c) at 12 Weeks	Change in HbA1c from baseline following 12 weeks of therapy (that is, HbA1c at week 12 minus HbA1c at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline HbA1c as a continuous covariate.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Fasting Glucose at 12 Weeks	Change in fasting glucose following 12 weeks of therapy (that is, fasting glucose at week 12 minus fasting glucose at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate.	Baseline, 12 weeks
Change From Baseline in Insulin Sensitivity (Fasting Insulin) at 12 Weeks	Change in serum fasting insulin from baseline to endpoint (that is, serum insulin at week 12 minus serum insulin at week 0). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate.	Baseline, 12 weeks
Number of Participants With a Change From Baseline in Beta-Cell Function Measured by Glucose and Insulin Changes With the Mixed Meal Tolerance Test (MMTT) at 12 Weeks	The number of participants with a change from baseline in glucose and insulin at 2 hours after the MMTT was analyzed. The MMTT measures glucose and insulin before and after a standardized meal is eaten. Glucose and insulin levels were measured before the MMTT and 2 hours after the MMTT.	Baseline, 12 weeks
Change From Baseline in the Glycosylated Hemoglobin (HbA1c) at Week 10 and Week 12	The change from baseline in HbA1c at week 10 (that is HbA1c at week 10 minus HbA1c at baseline) and week 12 (that is, HbA1c at week 12 minus HbA1c at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate.	Baseline, week 10, week 12
Pharmacokinetics (PK) Maximum Serum Concentration (Cmax) of LY2189102 at End of Dosing (12 Weeks)	The Cmax value measures the maximum serum concentration and is estimated for LY2189102. The values were generated as individual estimates from a population pharmacokinetics (PK) model. Placebo samples were not assayed for serum concentration of LY2189102 because the participants in the placebo treatment arm did not receive LY2189102 study drug.	Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose
PK: Area Under the Concentration Time Curve for Dosing Interval (Tau) at Steady State (AUCτ,SS) at End of Dosing (12 Weeks)	Individual estimates of AUCtau at end of dosing generated from a population pharmacokinetic (PK) model.	Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose
Pharmacokinetics Measured by Serum Concentration at End of Dosing (12 Weeks)	Pharmacokinetics Measured by Serum Concentration at End of Dosing.	Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Bihorel S, Fiedler-Kelly J, Ludwig E, Sloan-Lancaster J, Raddad E. Population pharmacokinetic modeling of LY2189102 after multiple intravenous and subcutaneous administrations. AAPS J. 2014 Sep;16(5):1009-17. doi: 10.1208/s12248-014-9623-6. Epub 2014 Jun 11.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: July 17, 2009
• First Submitted That Met QC Criteria: July 17, 2009
• First Posted (Estimate): July 20, 2009

Study Record Updates

• Last Update Posted (Actual): September 18, 2019
• Last Update Submitted That Met QC Criteria: September 6, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Diabetes; Type 2 Diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 13286; H9C-MC-BBDK (Other Identifier: Eli Lilly and Company)

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