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

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

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 Overview

• Status: Completed
• Conditions: Healthy; Type 2 Diabetes Mellitus (T2DM)
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo; Drug: Dulaglutide

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 117597
    • 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.
• United States
  • Florida
    • South Miami, Florida, United States, 33143
      • Miami Research Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirzepatide (Part A); Participants received escalating single doses of either 0.25 milligram (mg) or 0.5mg or 1mg, or 2.5mg or 5mg or 8mg Tirzepatide by subcutaneous injection.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Placebo Comparator: Placebo (Part A); Participants received single dose of placebo by subcutaneous injection.	Drug: Placebo; Administered SC
Experimental: Tirzepatide (Part B); Participants received fixed doses of either 0.5mg or 1.5mg or 4.5mg Tirzepatide once weekly for four weeks or titrated doses of 5mg, 5mg, 8mg and 10mg Tirzepatide once weekly for four weeks by subcutaneous injection.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Placebo Comparator: Placebo (Part B); Participants received placebo once weekly for four weeks by subcutaneous injection.	Drug: Placebo; Administered SC
Active Comparator: Dulaglutide (Part B); Participants received 1.5mg Dulaglutide once weekly for four weeks by subcutaneous injection.	Drug: Dulaglutide; Administered SC; Other Names: Trulicity®
Experimental: Tirzepatide (Part C); Participants received fixed doses of either 0.5mg or 5mg Tirzepatide once weekly for four weeks or titrated doses of 5mg,5mg,10mg,10mg or 5mg,5mg,10mg,15mg Tirzepatide once weekly for four weeks by subcutaneous injection	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Placebo Comparator: Placebo (Part C); Participants received placebo once weekly for four weeks by subcutaneous injection.	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)	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	Baseline through Day 43 (Part A) and Day 57 (Part B and C)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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).	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).	Pre-glucose dose, 0.5, 1, 1.5, 2 hours post-glucose dose on Day -1 and Day 23

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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), Eli Lilly and Company

Publications and helpful links

General Publications

• Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3.

Helpful Links

• Click here for more information about this study:A Study of tirzepatide in Participants With Type 2 Diabetes (T2DM)

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2016
• Primary Completion (Actual): June 26, 2017
• Study Completion (Actual): June 26, 2017

Study Registration Dates

• First Submitted: April 29, 2016
• First Submitted That Met QC Criteria: April 29, 2016
• First Posted (Estimated): May 3, 2016

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: April 1, 2023

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; Dulaglutide; Tirzepatide
• Other Study ID Numbers: 16119; I8F-MC-GPGA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR