A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone

Type 2 Diabetes Mellitus Clinical Trial

— SURPASS-1  

Official title:

A Randomized, Double-blind, Placebo-Controlled Trial Comparing the Efficacy and Safety of Three Tirzepatide Doses Versus Placebo in Patients With Type 2 Diabetes, Inadequately Controlled With Diet and Exercise Alone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03954834
• Other study ID #: 17000
• Secondary ID: I8F-MC-GPGK
• Status: Completed
• Phase: Phase 3
• Start date: June 3, 2019
• Est. completion date: October 28, 2020

Study information

• Verified date: October 2021
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal for this study is to evaluate the efficacy and safety of tirzepatide versus placebo in participants with type 2 diabetes not under control with diet and exercise alone. The study will last approximately 47 weeks and may include about 15 visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 478
• Est. completion date: October 28, 2020
• Est. primary completion date: October 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have been diagnosed with type 2 diabetes mellitus (T2DM).
• Are naïve to diabetes injectable therapies and have not used any oral antihyperglycemic medications (OAMs) during the 3 months preceding screening.
• Have HbA1c between =7.0% and =9.5%.
• Be of stable weight (± 5%) for at least 3 months before screening.
• Have a BMI =23 kilograms per meter squared (kg/m²) at screening.

Exclusion Criteria:

• Have type 1 diabetes mellitus.
• Have had chronic or acute pancreatitis any time prior to study entry.
• Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring acute treatment.
• Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss.
• Have an estimated glomerular filtration rate <30 mL/minute/1.73 m².
• Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months.
• Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2.
• Have been taking weight loss drugs, including over-the-counter medications during the last 3 months.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Tirzepatide
Administered SC
• Placebo
Administered SC

Locations

Country	Name	City	State
India	Dr. Jivraj Mehta Smarak Health Foundation	Ahmedabad	Gujarat
India	Bangalore Medical College and Research Institute	Bangalore	Karnataka
India	M S Ramaiah Medical College Hospital	Bangalore	Karnataka
India	Ramdevrao Hospital	Hyderabad	Telangana
India	BSES Municipal General Hsptl	Mumbai	Maharashtra
India	Ruby Hall Clinic and Grant Medical Foundation	Pune	Maharashtra
India	Gandhi Hospital	Telangana
India	Vijay Vallabh Hospital	Virar	Maharashtra
India	Lifepoint Multispecialty Hsptl	Wakad	Pune
Japan	Meiwa Hospital	Chiyodaku	Tokyo
Japan	Tokyo Center Clinic	Chuo-ku	Tokyo
Japan	Tokyo-Eki Center-building Clinic	Chuo-ku	Tokyo
Japan	Takai Naika Clinic	Kamakura	Kanagawa
Japan	IHL Shinagawa East One Medical Clinic	Minato-ku	Tokyo
Japan	Minamiakatsuka Clinic	Mito	Ibaraki
Japan	Sato Naika Clinic	Ota-ku	Tokyo
Japan	Takatsuki Red Cross Hospital	Takatsuki	Osaka
Japan	Tsuruma Kaneshiro Diabetes Clinic	Yamato	Kanagawa
Japan	Yokohama Minoru Clinic	Yokohama	Kanagawa
Mexico	Investigacion en Salud y Metabolismo S.C	Chihuahua
Mexico	Centro de Estudios de Investigacion Metabolicos y Cardiovasc	Madero	Tamaulipas
Mexico	Hospital Universitario UANL	Monterrey	Nuevo León
Mexico	Unidad Medica para la Salud Integral (UMSI)	Monterrey	Nuevo León
Puerto Rico	Clinical Research Puerto Rico, Inc.	San Juan
Puerto Rico	GCM Medical Group PSC	San Juan
United States	Agile Clinical Research Trials	Atlanta	Georgia
United States	Sky Clinical Research Network	Atlanta	Georgia
United States	Heritage Valley Medical Group, Inc.	Beaver	Pennsylvania
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Aventiv Research	Columbus	Ohio
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	The Corvallis Clinic P.C.	Corvallis	Oregon
United States	Dallas Diabetes Endocrine Center	Dallas	Texas
United States	Encore Medical Research, LLC	Hollywood	Florida
United States	National Research Institute	Huntington Park	California
United States	Family Medical Associates	Levittown	Pennsylvania
United States	National Research Institute	Los Angeles	California
United States	Axcess Medical Research	Loxahatchee Groves	Florida
United States	South Florida Wellness & Clinical Research Institute	Margate	Florida
United States	Suncoast Research Group, LLC	Miami	Florida
United States	Catalina Research Institute, LLC	Montclair	California
United States	Intend Research	Norman	Oklahoma
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Capital Clinical Research Center	Olympia	Washington
United States	National Research Institute	Panorama City	California
United States	Preferred Primary Care Physicians	Pittsburgh	Pennsylvania
United States	StudyMetrix Research, LLC	Saint Peters	Missouri
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Southern California Dermatology	Santa Ana	California
United States	Consano Clinical Research	Shavano Park	Texas
United States	Rockwood Clinic Research Center	Spokane	Washington
United States	Cotton O'Neil Clinic	Topeka	Kansas
United States	Preferred Primary Care Physicians	Uniontown	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  India,  Japan,  Mexico,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (HbA1c)	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Prior Use of oral antihyperglycemic medication (OAM) (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
Secondary	Change From Baseline in Body Weight	Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
Secondary	Percentage of Participants With HbA1c Target Value of <7%	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Week 40
Secondary	Change From Baseline in Fasting Serum Glucose	Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
Secondary	Percentage of Participants With HbA1c Target Value of <5.7%	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Week 40
Secondary	Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values	The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 40
Secondary	Percentage of Participants Who Achieved Weight Loss =5%	Percentage of Participants who Achieved Weight Loss =5%.	Week 40
Secondary	Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia	The hypoglycemia events were defined by participant reported events with blood glucose <54mg/dL) (<3.0 mmol/L] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment, with log (exposure in days/365.25) as an offset variable.	Baseline through end of safety follow-up (up to week 44)
Secondary	Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide	Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide. AUC is a combined measure obtained from Week 7, 15 and 23, and a single averaged measure of AUC was reported.	Week 7, 15 and 23

External Links

•   A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone (SURPASS-1)