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

Diabetes Mellitus, Type 2 Clinical Trial

— AWARD-9  

Official title:

A Randomized, Double-Blind Trial Comparing the Effect of Dulaglutide 1.5 mg With Placebo on Glycemic Control in Patients With Type 2 Diabetes on Basal Insulin Glargine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02152371
• Other study ID #: 13195
• Secondary ID: H9X-MC-GBDI2012-
• Status: Completed
• Phase: Phase 3
• Start date: May 2014
• Est. completion date: October 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Dulaglutide
Administered SQ
• Placebo
Administered SQ
• Insulin Glargine
Administered SQ
• Metformin
Administered orally

Locations

Country	Name	City	State
Czechia	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.	Beroun
Czechia	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.	Brandys Nad Labem-Stara Bolesl
Czechia	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.	Ceske Budejovice
Czechia	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.	Krnov
Czechia	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.	Prague
Hungary	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.	Budapest
Hungary	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.	Debrecen
Hungary	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.	Nagykanizsa
Italy	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.	Monza
Italy	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.	Olbia
Italy	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.	Pisa
Italy	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.	Rome
Puerto Rico	Centro de Endocrinologia y Nutricion del Turabo	Caguas
Puerto Rico	Manati Center for Clinical Research Inc	Manati
Puerto Rico	Endocrine Lipid Diabetes Research Institute	Ponce
Puerto Rico	Ponce School of Medicine CAIMED Center	Ponce
Puerto Rico	American Telemedicine Center	San Juan
Puerto Rico	GCM Medical Group PSC	San Juan
Spain	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.	Alzira
Spain	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.	Cadiz
Spain	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.	Madrid
Spain	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.	Sevilla
Spain	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.	Teruel
United Kingdom	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.	Guildford	Surrey
United Kingdom	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.	Leicester	Leicestershire
United Kingdom	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.	Mortimer	Berks
United Kingdom	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.	Swansea	Wales
United States	Northwest Endo Diabetes Research, LLC	Arlington Heights	Illinois
United States	Valley Endocrine, Fresno	Fresno	California
United States	Bland Clinic, PA	Greensboro	North Carolina
United States	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho
United States	PMG Research of Knoxville	Knoxville	Tennessee
United States	AB Clinical Trials	Las Vegas	Nevada
United States	Kentucky Diabetes Endocrinology Center	Lexington	Kentucky
United States	Rainier Clinical Research Center	Renton	Washington
United States	Mills-Peninsula Diabetes Research Insitute	San Mateo	California
United States	Polyclinic	Seattle	Washington
United States	SHS Clinical Research Group	Toms River	New Jersey
United States	Cotton O'Neil Clinic	Topeka	Kansas
United States	University Clinical Investigators, Inc.	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Czechia,  Hungary,  Italy,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to 28 Weeks 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) mean and standard error (SE) changes from baseline in HbA1c at 28 weeks were measured using mixed model regression and restricted maximum likelihood (REML) with treatment, pooled country, visit, and treatment-by -visit interaction as fixed effects, baseline as covariate, and participant as a random effect.	Baseline, 28 Weeks
Secondary	Change From Baseline to 28 Weeks in Fasting Serum Glucose (FSG)	FSG is a test to determine glucose levels after an overnight fast. LS means FSG change from baseline to primary endpoint at week 28 was calculated using a mixed effects model for repeated measures (MMRM) analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline FSG as covariate.	Baseline, 28 Weeks
Secondary	Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)	The LS means of the 7-point SMPG change from baseline to primary endpoint at week 28 was measured using a MMRM analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline SMPG as covariate.	Baseline, 28 Weeks
Secondary	Change From Baseline to 28 Weeks in Body Weight	LS means of the body weight change from baseline to primary endpoint at week 28 was adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline body weight as covariate, via a MMRM analysis.	Baseline, 28 Weeks
Secondary	Change From Baseline to 28 Weeks in Daily Mean Insulin Glargine Dose	Least Square (LS) Means of the insulin dose change from baseline to primary endpoint at week 28 was adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline insulin dose as covariate, via a MMRM analysis.	Baseline, 28 Weeks
Secondary	Number of Participants With Investigator Reported and Adjudicated Cardiovascular Events	Cardiovascular (CV) adverse events (AEs) were adjudicated by an independent committee of physicians with cardiology expertise external to the sponsor. Deaths occurring during the study treatment period and nonfatal CV AEs were to be adjudicated. Nonfatal CV events that were to be adjudicated were myocardial infarction; hospitalization for unstable angina; hospitalization for heart failure; coronary interventions (such as coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI); and cerebrovascular events, including cerebrovascular accident (CVA/stroke), and transient ischemic attack (TIA).	Baseline through 28 Weeks
Secondary	Percentage of Participants With Self-Reported Events of Hypoglycemia	Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The percentage of participants with self-reported hypoglycemic events is presented.	Baseline through 28 Weeks
Secondary	Percentage of Participants Discontinuing the Study Due to Severe, Persistent Hyperglycemia		Baseline through 28 Weeks
Secondary	Number of Participants With Adjudicated Acute Pancreatitis Events	The number of cases of acute pancreatitis confirmed by adjudication. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.	Baseline through 28 Weeks
Secondary	Number of Participants With Thyroid Tumors/Neoplasms (Including C-Cell Hyperplasia)		Baseline through 28 Weeks
Secondary	Number of Participants With Dulaglutide Anti-Drug Antibodies	Dulaglutide anti-drug antibodies (ADA) were assessed at baseline, Weeks 12 and 28. A participant was considered to have treatment-emergent (TE) dulaglutide ADAs if the participant had at least 1 titer that was TE relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.	Baseline, Week 12 and Week 28
Secondary	Percentage of Participants Achieving HbA1c Targets of <7.0% or =6.5%	Percentage of participants who achieved HbA1c levels of <7% or =6.5% were analyzed using a logistic regression model, controlling for treatment, pre-treatment, baseline HbA1c and country.	28 Weeks
Secondary	Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 Kilograms [kg]) at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)	Percentage of participants who achieved a target HbA1c target of <7%, without weight gain and without documented symptomatic hypoglycemia at 28 weeks were analyzed using regression model, controlling for treatment, pre-treatment, baseline HbA1c and country.	28 Weeks
Secondary	Percentage of Participants Achieving HbA1c Target of <7.0% at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)	Percentage of participants achieving target HbA1c of <7.0% at 28 weeks without documented symptomatic hypoglycemia are presented. Documented symptomatic hypoglycemia is defined as any time a participant experienced symptoms and or signs associated with hypoglycemia and had a plasma glucose of <=70 mg/dL.	28 Weeks
Secondary	Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 kg)		28 Weeks
Secondary	Rate of Hypoglycemic Events up to 28 Weeks	The rate of total hypoglycemic events any type per 30 days is presented. The hypoglycemia rate per 30 days during defined period is calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period*30 days.	Baseline through 28 Weeks