Clinical trial NCT04050553: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Hypoglycemia
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-08-08
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


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 \[including transient ischemic attack\])

Primary outcomes:
measure: 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
timeFrame: Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
Secondary outcomes:
measure: Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
timeFrame: Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
measure: Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
timeFrame: Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
measure: Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)
timeFrame: 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).
measure: 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)
timeFrame: Week 12.
measure: Mean Change in Blood Pressure From Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
timeFrame: Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
measure: Mean Change in Heart Rate From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
timeFrame: Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Universitätsklinikum Graz
state: Steiermark
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: