Clinical trial NCT02152371: A Study of Dulaglutide (LY2189265) in Participants With Type II Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2014-06-02
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Change From Baseline to 28 Weeks in Hemoglobin A1c (HbA1c)
timeFrame: Baseline, 28 Weeks
Secondary outcomes:
measure: Change From Baseline to 28 Weeks in Fasting Serum Glucose (FSG)
timeFrame: Baseline, 28 Weeks
measure: Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)
timeFrame: Baseline, 28 Weeks
measure: Change From Baseline to 28 Weeks in Body Weight
timeFrame: Baseline, 28 Weeks
measure: Change From Baseline to 28 Weeks in Daily Mean Insulin Glargine Dose
timeFrame: Baseline, 28 Weeks
measure: Number of Participants With Investigator Reported and Adjudicated Cardiovascular Events
timeFrame: Baseline through 28 Weeks
measure: Percentage of Participants With Self-Reported Events of Hypoglycemia
timeFrame: Baseline through 28 Weeks
measure: Percentage of Participants Discontinuing the Study Due to Severe, Persistent Hyperglycemia
timeFrame: Baseline through 28 Weeks
measure: Number of Participants With Adjudicated Acute Pancreatitis Events
timeFrame: Baseline through 28 Weeks
measure: Number of Participants With Thyroid Tumors/Neoplasms (Including C-Cell Hyperplasia)
timeFrame: Baseline through 28 Weeks
measure: Number of Participants With Dulaglutide Anti-Drug Antibodies
timeFrame: Baseline, Week 12 and Week 28
measure: Percentage of Participants Achieving HbA1c Targets of <7.0% or ≤6.5%
timeFrame: 28 Weeks
measure: 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)
timeFrame: 28 Weeks
measure: Percentage of Participants Achieving HbA1c Target of <7.0% at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)
timeFrame: 28 Weeks
measure: Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 kg)
timeFrame: 28 Weeks
measure: Rate of Hypoglycemic Events up to 28 Weeks
timeFrame: Baseline through 28 Weeks
Other outcomes:
Locations:
city: Fresno
country: United States
facility: Valley Endocrine, Fresno
state: California
city: San Mateo
country: United States
facility: Mills-Peninsula Diabetes Research Insitute
state: California
city: Tustin
country: United States
facility: University Clinical Investigators, Inc.
state: California
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes and Osteoporosis Center
state: Idaho
city: Arlington Heights
country: United States
facility: Northwest Endo Diabetes Research, LLC
state: Illinois
city: Topeka
country: United States
facility: Cotton O'Neil Clinic
state: Kansas
city: Lexington
country: United States
facility: Kentucky Diabetes Endocrinology Center
state: Kentucky
city: Las Vegas
country: United States
facility: AB Clinical Trials
state: Nevada
city: Toms River
country: United States
facility: SHS Clinical Research Group
state: New Jersey
city: Greensboro
country: United States
facility: Bland Clinic, PA
state: North Carolina
city: Knoxville
country: United States
facility: PMG Research of Knoxville
state: Tennessee
city: Renton
country: United States
facility: Rainier Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: Polyclinic
state: Washington
city: Beroun
country: Czechia
facility: 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.
city: Brandys Nad Labem-Stara Bolesl
country: Czechia
facility: 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.
city: Ceske Budejovice
country: Czechia
facility: 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.
city: Krnov
country: Czechia
facility: 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.
city: Prague
country: Czechia
facility: 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.
city: Budapest
country: Hungary
facility: 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.
city: Debrecen
country: Hungary
facility: 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.
city: Nagykanizsa
country: Hungary
facility: 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.
city: Monza
country: Italy
facility: 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.
city: Olbia
country: Italy
facility: 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.
city: Pisa
country: Italy
facility: 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.
city: Rome
country: Italy
facility: 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.
city: Caguas
country: Puerto Rico
facility: Centro de Endocrinologia y Nutricion del Turabo
city: Manati
country: Puerto Rico
facility: Manati Center for Clinical Research Inc
city: Ponce
country: Puerto Rico
facility: Ponce School of Medicine CAIMED Center
city: Ponce
country: Puerto Rico
facility: Endocrine Lipid Diabetes Research Institute
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC
city: San Juan
country: Puerto Rico
facility: American Telemedicine Center
city: Alzira
country: Spain
facility: 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.
city: Cadiz
country: Spain
facility: 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.
city: Madrid
country: Spain
facility: 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.
city: Sevilla
country: Spain
facility: 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.
city: Teruel
country: Spain
facility: 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.
city: Mortimer
country: United Kingdom
facility: 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.
state: Berks
city: Leicester
country: United Kingdom
facility: 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.
state: Leicestershire
city: Guildford
country: United Kingdom
facility: 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.
state: Surrey
city: Swansea
country: United Kingdom
facility: 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.
state: Wales
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Pantalone KM, Patel H, Yu M, Fernandez Lando L. Dulaglutide 1.5 mg as an add-on option for patients uncontrolled on insulin: Subgroup analysis by age, duration of diabetes and baseline glycated haemoglobin concentration. Diabetes Obes Metab. 2018 Jun;20(6):1461-1469. doi: 10.1111/dom.13252. Epub 2018 Mar 23.
citation: Yu M, Brunt KV, Milicevic Z, Varnado O, Boye KS. Patient-reported Outcomes in Patients with Type 2 Diabetes Treated with Dulaglutide Added to Titrated Insulin Glargine (AWARD-9). Clin Ther. 2017 Nov;39(11):2284-2295. doi: 10.1016/j.clinthera.2017.10.002. Epub 2017 Oct 27.