A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus
Primary Purpose
Diabetes Mellitus, Type 2, Hypoglycemia
Status
Completed
Phase
Phase 1
Locations
Austria
Study Type
Interventional
Intervention
Tirzepatide
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Diabetes Mellitus, Type 2
Eligibility Criteria
Inclusion Criteria:
- Have type 2 diabetes mellitus (T2DM) for at least 1 year
- Treated with diet and exercise and stable dose(s) of metformin 3 months prior to study entry with or without 1 additional oral antidiabetic medication (OAM) other than metformin.
- Have a hemoglobin A1c (HbA1c) value at screening of ≥6.5% and ≤9.0 % if on metformin only.
- Have a HbA1c value at screening of ≥6.0% and ≤8.5 %, if on metformin and 1 more allowed OAM.
- Have a body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m²) inclusive, at screening
- Are of stable weight (±5%) >3 months prior to screening
Exclusion Criteria:
- Have a history of proliferative retinopathy or maculopathy as determined by the investigator based on a recent (<6 months) ophthalmologic examination
- Impaired renal estimated glomerular filtration rate (eGFR) <60 milliliters per minute per 1.73 square meters (mL/min/1.73 m²) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs; of constituting a risk when taking the study drug; or of interfering with the interpretation of data
- Have had acute myocardial infarction, congestive heart failure New York Heart Association Class III or IV, history of or suspected ischemic heart disease, and/or cerebrovascular accident (stroke [including transient ischemic attack])
Sites / Locations
- Universitätsklinikum Graz
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tirzepatide
Placebo
Arm Description
Tirzepatide administered subcutaneously (SC) in one of two study periods.
Placebo administered SC in one of two study periods.
Outcomes
Primary Outcome Measures
Change in Mean Glucagon Concentration During Induced Hypoglycemia from Target Plasma Glucose (PG) Concentration of 100 Milligrams per Deciliter (mg/dL) to a Nadir Target of 45 mg/dL
Change in Mean Glucagon Concentration During Induced Hypoglycemia from Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Secondary Outcome Measures
Change in Mean Insulin Concentrations from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Change in Mean Insulin Concentrations from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Change in Mean C-peptide Concentrations from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Change in Mean C-peptide Concentrations from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Time from Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)
Time from Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)
Hypoglycemia Symptoms Score from Induced Hypoglycemia at Target PG Concentrations of 100 mg/dL, 63 mg/dL, 45 mg/dL and Recovery (PG Concentration 72 mg/dL)
Hypoglycemia Symptoms Score from Induced Hypoglycemia at Target PG Concentrations of 100 mg/dL, 63 mg/dL, 45 mg/dL and Recovery (PG Concentration 72 mg/dL)
Mean Change in Blood Pressure from Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Mean Change in Blood Pressure from Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Mean Change in Heart Rate from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Mean Change in Heart Rate from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Full Information
NCT ID
NCT04050553
First Posted
August 7, 2019
Last Updated
February 24, 2022
Sponsor
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT04050553
Brief Title
A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus
Official Title
A Randomized, Placebo-Controlled, Crossover Study to Investigate the Effect of Once-Weekly Tirzepatide on the Counter-Regulatory Response to Hypoglycemia in Patients With Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
February 24, 2020 (Actual)
Primary Completion Date
January 25, 2022 (Actual)
Study Completion Date
January 25, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main purpose of this study is to learn more about how tirzepatide affects the body's response to low blood sugar (hypoglycemia). The study is open to participants with type 2 diabetes. It will last about 42 weeks for each participant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, Hypoglycemia
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tirzepatide
Arm Type
Experimental
Arm Description
Tirzepatide administered subcutaneously (SC) in one of two study periods.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo administered SC in one of two study periods.
Intervention Type
Drug
Intervention Name(s)
Tirzepatide
Other Intervention Name(s)
LY3298176
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered SC
Primary Outcome Measure Information:
Title
Change in Mean Glucagon Concentration During Induced Hypoglycemia from Target Plasma Glucose (PG) Concentration of 100 Milligrams per Deciliter (mg/dL) to a Nadir Target of 45 mg/dL
Description
Change in Mean Glucagon Concentration During Induced Hypoglycemia from Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Time Frame
Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level
Secondary Outcome Measure Information:
Title
Change in Mean Insulin Concentrations from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Description
Change in Mean Insulin Concentrations from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Time Frame
Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose
Title
Change in Mean C-peptide Concentrations from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Description
Change in Mean C-peptide Concentrations from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Time Frame
Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose
Title
Time from Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)
Description
Time from Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)
Time Frame
Week 12 in each treatment period (treatment period = 12 weeks): 1 minute after reaching the nadir glucose level and when reaching normoglycemia (estimated as 30 mins)
Title
Hypoglycemia Symptoms Score from Induced Hypoglycemia at Target PG Concentrations of 100 mg/dL, 63 mg/dL, 45 mg/dL and Recovery (PG Concentration 72 mg/dL)
Description
Hypoglycemia Symptoms Score from Induced Hypoglycemia at Target PG Concentrations of 100 mg/dL, 63 mg/dL, 45 mg/dL and Recovery (PG Concentration 72 mg/dL)
Time Frame
Week 12 in each treatment period (treatment period = 12 weeks): 1 minute after reaching the nadir glucose level and when reaching normoglycemia (estimated as 30 mins)
Title
Mean Change in Blood Pressure from Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Description
Mean Change in Blood Pressure from Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Time Frame
Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose
Title
Mean Change in Heart Rate from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Description
Mean Change in Heart Rate from Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
Time Frame
Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have type 2 diabetes mellitus (T2DM) for at least 1 year
Treated with diet and exercise and stable dose(s) of metformin 3 months prior to study entry with or without 1 additional oral antidiabetic medication (OAM) other than metformin.
Have a hemoglobin A1c (HbA1c) value at screening of ≥6.5% and ≤9.0 % if on metformin only.
Have a HbA1c value at screening of ≥6.0% and ≤8.5 %, if on metformin and 1 more allowed OAM.
Have a body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m²) inclusive, at screening
Are of stable weight (±5%) >3 months prior to screening
Exclusion Criteria:
Have a history of proliferative retinopathy or maculopathy as determined by the investigator based on a recent (<6 months) ophthalmologic examination
Impaired renal estimated glomerular filtration rate (eGFR) <60 milliliters per minute per 1.73 square meters (mL/min/1.73 m²) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs; of constituting a risk when taking the study drug; or of interfering with the interpretation of data
Have had acute myocardial infarction, congestive heart failure New York Heart Association Class III or IV, history of or suspected ischemic heart disease, and/or cerebrovascular accident (stroke [including transient ischemic attack])
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Universitätsklinikum Graz
City
Graz
State/Province
Steiermark
ZIP/Postal Code
8036
Country
Austria
12. IPD Sharing Statement
Plan to Share IPD
No
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A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus
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