Clinical trial NCT03131687: A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Mellitus
Official title: A Phase 2 Study of Once-Weekly LY3298176 Compared With Placebo and Dulaglutide in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2017-04-27
Enrollment: 318
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of the study drug tirzepatide in participants with type 2 diabetes mellitus.


Eligibility criteria: Inclusion Criteria:

* Have had type 2 diabetes (T2D) for ≥6 months according to the World Health Organization (WHO) classification.
* Have HbA1c of 7.0% to 10.5%, inclusive, as assessed by the central laboratory.
* If on metformin, have been treated with stable doses of metformin for at least 3 months.
* Have a body mass index (BMI) ≥23 and \<50 kilograms per square meter.

Exclusion Criteria:

* Have type 1 diabetes (T1D).
* Have used any glucose-lowering medication other than metformin within 3 months prior to study entry or during screening/lead-in period or have used any glucagon-like peptide-1 receptor agonists (GLP-1 RAs) at any time in the past.
* Have had any of the following cardiovascular conditions: acute myocardial infarction (MI), New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident (stroke).
* Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level \>2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial.
* Have had chronic or acute pancreatitis any time prior to study entry.
* Have an estimated glomerular filtration rate (eGFR) \<45 milliliters/minute/1.73 square meter, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation.
* Have serum calcitonin ≥20 picograms per milliliter, as determined by the central laboratory at study entry.
* Have any condition that is a contraindication for use of the GLP-1 RA class (per country-specific labels) at study entry or develop such condition between study entry and randomization.

Primary outcomes:
measure: Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) Bayesian Dose Response
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) Bayesian Dose Response
timeFrame: Baseline, Week 12
measure: Change From Baseline to Week 26 in HbA1c
timeFrame: Baseline, Week 26
measure: Change From Baseline to Week 12 in HbA1c
timeFrame: Baseline, Week 12
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Week 26
measure: Percentage of Participants With 5% or Greater Body Weight Loss From Baseline
timeFrame: Week 26
measure: Percentage of Participants With 10% or Greater Body Weight Loss From Baseline
timeFrame: Week 26
measure: Percentage of Participants Reaching the HbA1c Target of ≤6.5%
timeFrame: Week 26
measure: Percentage of Participants Reaching the HbA1c Target of <7.0%
timeFrame: Week 26
measure: Change From Baseline in Fasting Blood Glucose
timeFrame: Baseline, Week 26
measure: Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline, Week 26
measure: Change From Baseline in Total Cholesterol
timeFrame: Baseline, Week 26
measure: Change From Baseline in Triglycerides
timeFrame: Baseline, Week 26
measure: Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline, Week 26
measure: Change From Baseline in Waist Circumference
timeFrame: Baseline, Week 26
measure: Number of Participants With Anti-Drug Antibodies
timeFrame: Baseline through Week 30
measure: Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide
timeFrame: Predose: Week 1,8,12 and 26; Postdose: Week 1,2,4 and 12
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Internal Medicine Center LLC
state: Alabama
city: Anaheim
country: United States
facility: Anaheim Clinical Trails
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
city: Northridge
country: United States
facility: Valley Clinical Trails, Inc
state: California
city: San Diego
country: United States
facility: Artemis Institute For Clinical Research
state: California
city: San Marcos
country: United States
facility: Artemis Institute For Clinical Research
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Tustin
country: United States
facility: University Clinical Investigators INC
state: California
city: Waterbury
country: United States
facility: Chase Medical Research
state: Connecticut
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute For Research
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group, LCC
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Ocoee
country: United States
facility: Sensible Healthcare
state: Florida
city: Palm Harbor
country: United States
facility: Palm Harbor Medical Associate
state: Florida
city: Meridian
country: United States
facility: Solaris Clinical Research
state: Idaho
city: West Des Moines
country: United States
facility: Iderc P.L.C.
state: Iowa
city: Topeka
country: United States
facility: Cotton O'Neil Diabetes and Endocrine
state: Kansas
city: Methuen
country: United States
facility: ActivMed Practices & Research
state: Massachusetts
city: Saint Louis
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Las Vegas
country: United States
facility: Palm Research Center
state: Nevada
city: Trenton
country: United States
facility: Premier Research
state: New Jersey
city: New York
country: United States
facility: Manhattan Medical Research
state: New York
city: Fargo
country: United States
facility: Lillestol Research LLC
state: North Dakota
city: Columbus
country: United States
facility: Aventiv Research
state: Ohio
city: Corvallis
country: United States
facility: The Corvallis Clinic P.C.
state: Oregon
city: Moncks Corner
country: United States
facility: PMG Research Of Charleston LLC
state: South Carolina
city: Knoxville
country: United States
facility: New Phase Research & Development
state: Tennessee
city: Knoxville
country: United States
facility: PMG Research Of Knoxville
state: Tennessee
city: Dallas
country: United States
facility: Dallas Diabetes Endocrine Center
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research
state: Texas
city: Saint George
country: United States
facility: Chrysalis Clinical Research
state: Utah
city: Gdańsk
country: Poland
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Gdynia
country: Poland
facility: "For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician."
city: Gdynia
country: Poland
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Katowice
country: Poland
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Szczecin
country: Poland
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Łódź
country: Poland
facility: Clinica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária LTDA
city: Manati
country: Puerto Rico
facility: Manati Center for Clinical Research
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico. Inc
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC
city: Košice
country: Slovakia
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: Malacky
country: Slovakia
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: Púchov
country: Slovakia
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: Trenčín
country: Slovakia
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: Trenčín
country: Slovakia
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
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: Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, Zoungas S. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022 Mar;28(3):591-598. doi: 10.1038/s41591-022-01707-4. Epub 2022 Feb 24.
citation: Pirro V, Roth KD, Lin Y, Willency JA, Milligan PL, Wilson JM, Ruotolo G, Haupt A, Newgard CB, Duffin KL. Effects of Tirzepatide, a Dual GIP and GLP-1 RA, on Lipid and Metabolite Profiles in Subjects With Type 2 Diabetes. J Clin Endocrinol Metab. 2022 Jan 18;107(2):363-378. doi: 10.1210/clinem/dgab722.
citation: Hartman ML, Sanyal AJ, Loomba R, Wilson JM, Nikooienejad A, Bray R, Karanikas CA, Duffin KL, Robins DA, Haupt A. Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes. Diabetes Care. 2020 Jun;43(6):1352-1355. doi: 10.2337/dc19-1892. Epub 2020 Apr 14.
citation: Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, Urva S, Gimeno RE, Milicevic Z, Robins D, Haupt A. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018 Nov 17;392(10160):2180-2193. doi: 10.1016/S0140-6736(18)32260-8. Epub 2018 Oct 4.