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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Tirzepatide

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Hachioji, Tokyo, Japan, 192-0071
      • 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.
    • Shinjuku-Ku, Tokyo, Japan, 169-0073
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirzepatide; 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; Administered SC.; Other Names: LY3298176
Placebo Comparator: Placebo; Participants received placebo administered into the SC tissue of the abdominal wall.	Drug: Placebo; Administered SC.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2017
• Primary Completion (Actual): May 29, 2018
• Study Completion (Actual): November 28, 2018

Study Registration Dates

• First Submitted: October 24, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 26, 2017

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: 16400; I8F-JE-GPGC (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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