A Study of Tirzepatide (LY3298176) in Healthy Participants and Participants With Type 2 Diabetes (T2DM)

Eli Lilly and Company142 enrolled

Overview

The main purposes of this study are to determine: * The safety of tirzepatide and any side effects that might be associated with it. * How much tirzepatide gets into the bloodstream and how long it takes the body to get rid of it. * How tirzepatide affects the levels of blood sugar. This study includes 3 parts (A, B and C). Part A involves a single dose of tirzepatide taken as a subcutaneous (SC) injection just under the skin and will be approximately 10 weeks in duration, including screening. Parts B and C involve 4 doses of tirzepatide taken once weekly (over 4 weeks) as a SC injection just under the skin and is approximately 12-14 weeks in duration, including screening. Each participant will enroll in only one part. This study is for research purposes only, and is not intended to treat any medical condition.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

142

Conditions

Healthy Type 2 Diabetes Mellitus (T2DM)

Interventions

Eligibility

Sex: ALLMin age: 21 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy participants (Parts A and B) and participants with T2DM diagnosed at least 1 year before enrollment (Part C) * Have a screening body mass index (BMI) of greater than 18.5 and less than or equal to 40.0 kilograms per meter squared (kg/m²), inclusive * Participants with T2DM (Part C only): have T2DM controlled with diet and exercise alone or are stable on a single oral antidiabetic medication (metformin for at least 30 days or sulfonylureas). Participants receiving sulfonylureas may participate only if this treatment is stopped for at least 6 weeks before dosing with study drug Exclusion Criteria: * Have known allergies to tirzepatide, glucagon-like peptide (GLP)-1 analogs, or related compounds * Have an abnormality in the 12-lead electrocardiogram (ECG) at screening that, in the opinion of the investigator, increases the risks associated with participating in the study * Have a history or presence of pancreatitis (history of chronic pancreatitis or idiopathic acute pancreatitis), elevation in serum amylase or lipase (greater than 2-fold the upper limit of normal \[ULN\]) or gastrointestinal (GI) disorder (for example, relevant esophageal reflux or gall bladder disease) or any GI disease which impacts gastric emptying (for example, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by glucagon-like peptide-1 (GLP-1) analogs or dipeptidyl peptidase (DPP)-IV inhibitors Participants with T2DM (Part C only) * Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before entry into the study or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms All Study Participants (Parts B and C only) * have known allergies to tirzepatide, GLP-1 analogs, or related compounds, or acetaminophen

Locations (2)

Miami Research Associates

South Miami, Florida, United States

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.

Singapore, Singapore

Outcomes

Primary Outcomes

Number of Participants With One or More Serious Adverse Event(s) (SAEs)

Number of participants with one or more SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module

Time frame: Baseline through Day 43 (Part A) and Day 57 (Part B and C)

Secondary Outcomes

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part A.

Area under the concentration versus time curve from zero to infinity (AUC \[0-∞\]) of Tirzepatide in Part A.

Time frame: Predose, 8hours(h), 24h,48h,72h,96h,120h,168h,336h postdose, day 29, day 43

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part B

Area under the concentration versus time curve during 1 dosing interval (AUC \[0-τ\]) of Tirzepatide in Part B. τ equals 168 hours.

Time frame: Predose, 8hours(h), 24h,48h,72h,168h postdose

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part C

Area under the concentration versus time curve during 1 dosing interval (AUC \[0-τ\]) of Tirzepatide in Part C. τ equals 168 hours.

Time frame: Predose, 8hours(h), 24h,48h,72h,168h postdose

Pharmacodynamics (PD): Ratio of AUC of Glucose on Day 2 to Baseline (Part C)

PD: Glucose area under the concentration versus time curve from time 0 to 2 hours (AUC\[0-2h\]) in Part C. Ratio to Baseline (Day -1) AUC (0-2h).

Time frame: Pre-glucose dose, 0.5, 1, 1.5, 2 hours post-glucose dose on Day -1 and Day 2

Pharmacodynamics (PD): Ratio of AUC of Glucose on Day 23 to Baseline (Part C)

PD: Glucose area under the concentration versus time curve from time 0 to 2 hours (AUC\[0-2h\]) in Part C. Ratio to Baseline (Day -1) AUC (0-2h).

Time frame: Pre-glucose dose, 0.5, 1, 1.5, 2 hours post-glucose dose on Day -1 and Day 23