A Study of Tirzepatide (LY3298176) in Japanese Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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The 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 remove it. How tirzepatide affects the levels of blood sugar. This study includes eight weekly doses of tirzepatide or placebo given as subcutaneous (SC) injections just under the skin. The study will last about 16 weeks (total), including screening and follow-up. This study is for research purposes only and is not intended to treat any medical conditions.

Official Title
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A Multiple-Ascending Dose Study in Japanese Patients With Type 2 Diabetes Mellitus to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3298176

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Tirzepatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have T2DM controlled with diet and exercise alone or are stable on a single oral antidiabetic medication (metformin or dipeptidyl peptidase [DPP]-IV inhibitors) Have a body mass index of 20.0 to 35.0 kilograms per square meter, inclusive Exclusion Criteria: Have known allergies to tirzepatide, glucagon-like peptide (GLP)-1 analogs, or related compounds 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 Have an abnormality in the 12-lead electrocardiogram 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 or gastrointestinal (GI) disorder or any GI disease which impacts gastric emptying or could be aggravated by GLP-1 analogs or DPP-IV inhibitors

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirzepatide<br>Participants received escalating doses of 2.5 milligrams (mg), 5 mg, 10 mg and 15 mg of tirzepatide administered into the subcutaneous (SC) tissue of the abdominal wall. | Drug: Tirzepatide<br>* Administered SC.<br>* Other names: LY3298176;|
| Placebo Comparator: Placebo<br>Participants received placebo administered into the SC tissue of the abdominal wall. | Drug: Placebo<br>* Administered SC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Safety was assessed from time of consent through end of study (up to 85 days). Data presented are the number of participants who experienced 1 or more SAEs considered by the investigator to be related to study drug. A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this record. | Baseline through Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Tirzepatide | Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of Tirzepatide in plasma. | Predose, 8, 24, 48, 72 and 168 hours post dose for Day 1 administration, and Predose, 8, 24, 48, and 168 hours post dose for Day 50 administration | 
| PK: Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide | Area under the concentration versus time curve from time zero to tau (τ) of Tirzepatide (AUC[0- τ]), where tau is dosing interval of (0-168 hours). | Predose, 8, 24, 48, 72 and 168 hours post dose for Day 1 administration, and Predose, 8, 24, 48, and 168 hours post dose for Day 50 administration | 
| Pharmacodynamics (PD): Change From Baseline to 8 Weeks in Fasting Plasma Glucose | Change from baseline to 8 weeks in Fasting Plasma Glucose was measured to investigate the PD effect of Tirzepatide after multiple SC doses administered to Japanese patients with T2DM | Baseline, Week 8 |