A Study of Dulaglutide (LY2189265) in Participants With Type II Diabetes (AWARD-9)

Lilly

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Dulaglutide; Drug: Placebo; Drug: Insulin Glargine; Drug: Metformin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02152371

13195

H9X-MC-GBDI (Other Identifier)

2012-004229-25 (EudraCT Number)

Details and patient eligibility

About

The main purpose of this study is to evaluate the use of the study drug known as dulaglutide in participants with type II diabetes who are taking once-daily insulin glargine. The study will last about 31 weeks for each participant.

Enrollment: 300 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have type 2 diabetes (based on the World Health Organization's [WHO] diagnostic criteria)

• Have been treated with basal insulin glargine once daily with or without metformin for at least 3 months prior to screening

• Doses of once daily insulin glargine and metformin (if taken) must be stable during the 3-month period prior to screening. Doses of metformin are considered stable if all prescribed doses during this period are in the range between the minimum required dose (≥1500 mg/day) and the maximum approved dose per the locally-approved label

• Have an HbA1c value ≥7.0% and ≤10.5% as assessed by the central laboratory at screening

• Require further insulin glargine dose increase at week 3 per the treat-to-target (TTT) algorithm based on the SMPG data collected during the prior week

• Have stable weight (±5%) ≥3 months prior to screening

• Have body mass index (BMI) ≤45 kilograms per square meter (kg/m^2) at screening

• Are able and willing to administer once weekly randomized therapy

• Are females of childbearing potential who must:

  • Test negative for pregnancy at screening, based on a serum pregnancy test
  • Agree to use a reliable method of birth control
  • Not be breastfeeding

Exclusion criteria

• Have been treated with ANY other antihyperglycemia regimen, other than basal insulin glargine once daily with or without metformin, within the 3 months prior to screening or between screening and week 3
• Have a history of ≥1 episode of ketoacidosis or hyperosmolar state/coma
• Have a history of hypoglycemia unawareness within the 6 months prior to screening
• Have been treated with drugs that promote weight loss within the 3 months prior to screening or between screening and week 3
• Are receiving chronic (>14 days) systemic glucocorticoid therapy or have received such therapy within the 4 weeks prior to screening or between screening and week 3
• Have had any of the following cardiovascular conditions within the 2 months prior to screening: acute myocardial infarction (MI), New York Heart Association (NYHA) Class III or Class IV heart failure, or cerebrovascular accident (stroke)
• Have a known clinically significant gastric emptying abnormality or have undergone gastric bypass surgery or restrictive bariatric surgery
• Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or alanine aminotransferase (ALT) level >2.5 times the upper limit of the reference range, as determined by the central laboratory
• Have a history of chronic pancreatitis or acute idiopathic pancreatitis, or were diagnosed with any type of acute pancreatitis within the 3 months prior to screening
• Have an estimated glomerular filtration rate (eGFR) <30 milliliters/minute/1.73 square meter (mL/min/m^2), calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, as determined by the central laboratory; for participants on metformin, have renal disease or renal dysfunction (for example, a serum creatinine ≥1.5 mg/deciliter [dL] [male] or ≥1.4 mg/dL [female] or eGFR [CKD-EPI] <60 mL/min/1.73 m^2)
• Have evidence of a significant, uncontrolled endocrine abnormality
• Have any self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B) in the absence of known C-cell hyperplasia
• Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, or carcinoma (including sporadic, familial, or part of MEN 2A or 2B syndrome)
• Have serum calcitonin ≥20 picograms/mL, as determined by the central laboratory
• Have evidence of a significant, active autoimmune abnormality
• Have any other condition not listed in this section that is a contraindication for use of insulin glargine, or, for participants using metformin, have a condition that is a contraindication for the use of metformin and would require metformin discontinuation per label
• Have a history of transplanted organ
• Have a history of active or untreated malignancy, or are in remission from a clinically significant malignancy during the 5 years prior to screening
• Have a history of any other condition which, in the opinion of the investigator, may preclude the participants from following and completing the protocol
• Have any hematologic condition that may interfere with HbA1c measurement (eg, hemolytic anemias, sickle-cell disease)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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300 participants in 2 patient groups, including a placebo group

Dulaglutide + Insulin Glargine

Experimental group

Description:

1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.

Treatment:

Drug: Metformin

Drug: Insulin Glargine

Drug: Dulaglutide

Placebo + Insulin Glargine

Placebo Comparator group

Description:

Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.

Treatment:

Drug: Metformin

Drug: Insulin Glargine

Drug: Placebo