A Study in Participants With Type 2 Diabetes Mellitus (AWARD-1)

Lilly

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Exenatide; Drug: Placebo; Drug: Metformin; Drug: LY2189265; Drug: Pioglitazone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01064687

11373

H9X-MC-GBDA (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to determine if LY2189265 is effective and safe in reducing hemoglobin A1c (HbA1c), as compared to placebo (no medicine), or exenatide in participants with Type 2 Diabetes. The participants must also be taking metformin and pioglitazone.

Full description

During the study, if a participant developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, the participant received additional therapeutic intervention or initiation of an alternative antihyperglycemic medication following study drug discontinuation (rescue therapy). Participants who received rescue therapy were included in the analysis population, but only measurements obtained prior to the beginning of rescue therapy were included in specified analyses.

Enrollment: 978 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 2 Diabetes (T2D) not well controlled on 1, 2, or 3 oral antidiabetic medications

  1. Glycosylated hemoglobin (HbA1c) greater than or equal to 7 and less than or equal to 11 if taking 1 oral antidiabetic medication
  2. HbA1c greater than or equal to 7 and less than or equal to 10 if on 2 or 3 oral antidiabetic medications

• Able to tolerate minimum dose of 1500 milligrams (mg) metformin a day and 30 mg pioglitazone per day.

• Willing to inject subcutaneous (SC) medication up to 2 times per day

• Stable weight for 3 months prior to screening

• Body mass index (BMI) between 23 and 45 kilograms per meter squared (kg/m^2)

• Females of child bearing potential must test negative for pregnancy at screening by serum pregnancy test and be willing to use a reliable method of birth control during the study and for 1 month following the last dose of study drug.

Exclusion criteria

• Type 1 Diabetes
• HbA1c equal to or less than 6.5 before randomization or at randomization
• Chronic insulin use
• Taking drugs to promote weight loss by prescription or over the counter
• Taking systemic steroids for greater than 14 days except for topical, eye, nasal, or inhaled
• History of fluid retention or edema
• History of Heart Failure New York Heart Classification II, III, or IV or acute myocardial infarction or stroke within 2 months of screening
• Gastrointestinal (GI; stomach) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking drugs that directly affect GI motility
• Hepatitis or liver disease or alanine transaminase (ALT) greater than 2.5 times the upper limit of normal
• Acute or chronic pancreatitis of any form
• Renal disease (kidney) with a serum creatinine of greater than or equal to 1.5 milligrams per deciliter (mg/dL) for males and greater than or equal to 1.4 mg/dL for females, or a creatine clearance of less than 60 milliliters per minute (mL/min)
• History (includes family) of type 2A or 2B Multiple Endocrine Neoplasia (MEN 2A or 2B) or medullary c-cell hyperplasia or thyroid cancer
• A serum calcitonin greater than or equal to 20 picograms per milliliter (pg/mL) at screening
• Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis
• History of or active malignancy except skin or in situ cervical or prostate cancer for within last 5 years
• Sickle cell, hemolytic anemia, or other hematological condition that may interfere with HbA1c testing
• Organ transplant except cornea
• Have enrolled in another clinical trial within the last 30 days
• Have previously signed an informed consent or participated in a LY2189265 (dulaglutide) study
• Have taken a glucagon-like peptide 1 (GLP-1) receptor agonist within the 3 months prior to screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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978 participants in 4 patient groups, including a placebo group

1.5 mg LY2189265

Experimental group

Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks

Treatment:

Drug: LY2189265

Drug: Pioglitazone

Drug: Metformin

0.75 mg LY2189265

Experimental group

Description:

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks

Treatment:

Drug: LY2189265

Drug: Pioglitazone

Drug: Metformin

Exenatide

Active Comparator group

Description:

Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks

Treatment:

Drug: Exenatide

Drug: Pioglitazone

Drug: Metformin

Placebo

Placebo Comparator group

Description:

Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): After 26 weeks, participants were randomized to receive either 0.75 milligrams (mg) or 1.5 mg, SC, once weekly for an additional 26 weeks (from week 26 through week 52). Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks

Treatment:

Drug: Placebo

Drug: LY2189265

Drug: Pioglitazone

Drug: Metformin