A Study of LY3502970 in Healthy Participants

A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3502970 in Healthy Subjects

The main purposes of this study are to determine:

• The safety of LY3502970 and any side effects that might be associated with it.
• How much LY3502970 gets into the bloodstream and how long it takes the body to get rid of it.

This study has 5 parts (A, B, C, D, and E). Parts A and D involve a single dose of LY3502970 and will last about 15 days. Part B and E involve multiple doses of LY3502970 and will last about 4 weeks. Part C involves two single doses of LY3502970 and will last about 29 days. Each participant will enroll in only one part. Screening must be completed within 28 days before study start. This study is for research purposes only, and is not intended to treat any medical condition.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Midazolam; Drug: Placebo; Drug: LY3502970; Drug: Atorvastatin; Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male or females, as determined by medical history
• Have safety laboratory results within normal reference ranges

Exclusion Criteria:

• Have known allergies to LY3502970, glucagon-like peptide-1 (GLP-1) analogs, related compounds
• Abnormal electrocardiogram (ECG) at screening
• Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological or neurological disorders.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

17

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A 0.3 mg LY3502970; Participants received a single oral dose of 0.3 milligram (mg) LY3502970.	Drug: LY3502970; Administered orally.
Experimental: Part A 1 mg LY3502970; Participants received a single oral dose of 1 mg LY3502970.	Drug: LY3502970; Administered orally.
Experimental: Part A 3 mg LY3502970; Participants received a single oral dose of 3 mg LY3502970.	Drug: LY3502970; Administered orally.
Experimental: Part A 6 mg LY3502970; Participants received a single oral dose of 6 mg LY3502970.	Drug: LY3502970; Administered orally.
Placebo Comparator: Part A Placebo; Participants received a single oral dose of Placebo.	Drug: Placebo; Administered orally.
Placebo Comparator: Part B Placebo; Participants received oral doses of placebo once daily for 4 weeks.	Drug: Placebo; Administered orally.
Experimental: Part B: 2 mg LY3502970 (Cohort G); Participants received oral doses of 2 mg LY3502970 once daily for 4 weeks.	Drug: LY3502970; Administered orally.
Experimental: Part B: 2 / 4 / 6 mg LY3502970 (Cohort H); Participants received oral doses of LY3502970 once daily for 4 weeks where 2 mg was given for first week, 4 mg for second week followed by 6 mg on the third and fourth week.	Drug: LY3502970; Administered orally.
Experimental: Part B: 2 / 4 / 8 / 16 mg LY3502970 (Cohort I); Participants received oral doses of LY3502970 once daily for 4 weeks where 2 mg was given for first week, 4 mg for second week, 8 mg for third week and 16 mg for fourth week.	Drug: LY3502970; Administered orally.
Experimental: Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort J); Participants received oral doses of LY3502970 once daily for 4 weeks, where 2 mg was given on first week, 5 mg on second week, 12 mg on third week and 24 mg on fourth week. On day 27, midazolam 200 microgram (mcg) was coadministered with 24 mg LY3502970, and 40 mg atorvastatin administered 4 hours after midazolam.	Drug: Midazolam; Administered orally.; Drug: LY3502970; Administered orally.; Drug: Atorvastatin; Administered orally.
Experimental: Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort K); Participants received oral doses of LY3502970 once daily for 4 weeks, where 2 mg was given on first week, 5 mg on second week, 12 mg on third week and 24 mg on fourth week. On day 27, 20 mg simvastatin was coadministered with 24 mg LY3502970.	Drug: LY3502970; Administered orally.; Drug: Simvastatin; Administered orally.
Experimental: Part C: 3 mg LY3502970 (Fasted/Fed); Part C of the study is exploratory, conducted to study exploratory objectives. Participants received a single oral dose of 3 mg LY3502970 in treatment period 1 (fasted condition), followed by administration in treatment period 2 (fed condition), with a washout period of at least 5 days between periods.	Drug: LY3502970; Administered orally.
Experimental: Part C: 3 mg LY3502970 (Fed/Fasted); Part C of the study is exploratory, conducted to study exploratory objectives. Participants received a single oral dose of 3 mg LY3502970 in treatment period1 (fed condition), followed by administration in treatment period 2 (fasted condition), with a washout period of at least 5 days between periods.	Drug: LY3502970; Administered orally.
Active Comparator: Part D: 3 mg LY3502970 Prototype Formulation; Part D of the study is exploratory, conducted to study exploratory objectives. Participants received a single oral dose of 3 mg LY3502970 in a controlled-release prototype formulation.	Drug: LY3502970; Administered orally.
Placebo Comparator: Part D: Placebo Prototype Formulation; Part D of the study is exploratory, conducted to study exploratory objectives. Participants received a single oral dose of placebo in a controlled-release prototype formulation.	Drug: Placebo; Administered orally.
Experimental: Part E: 2 / 5 / 12 / 24 mg LY3502970 (24 mg as Formulation 1); Part E of the study is exploratory, conducted to study exploratory objectives. Participants received oral doses of LY3502970 once daily for 4 weeks where 2 mg was given for first week, 5 mg for second week, 12 mg for third week and 24 mg as formulation 1 for the fourth week.	Drug: LY3502970; Administered orally.
Experimental: Part E: 2 / 5 / 12 / 24 mg LY3502970 (24 mg as Formulation 2); Part E of the study is exploratory, conducted to study exploratory objectives. Participants received oral doses of LY3502970 once daily for 4 weeks where 2 mg was given for first week, 5 mg for second week, 12 mg for third week and 24 mg as formulation 2 for the fourth week.	Drug: LY3502970; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A and B: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug	An SAE is any adverse event from this study that results in 1 of the following: Death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent 1 of the other outcomes listed in the definition above. The number of participants with one or more SAEs considered by the investigator to be related to study drug administration is reported. An overall summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.	Baseline through Follow-up (up to Day 42)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3502970	PK: Cmax of LY3502970	Pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post-dose
Part A: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-tlast]) of LY3502970	PK: AUC(0-tlast) of LY3502970	Pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post-dose
Part A: PK: Time of Maximum Observed Concentration (Tmax) of LY3502970	PK: Tmax of LY3502970	Pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post-dose
Part B: PK: Maximum Observed Concentration (Cmax) of LY3502970 on Day 1	PK: Cmax of LY3502970	Day 1 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24 hours post-dose)
Part B: PK: Maximum Observed Concentration (Cmax) of LY3502970 on Day 28	PK: Cmax of LY3502970	Day 28 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 96, 168, 336 hours post-dose)
Part B: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-tlast]) of LY3502970 on Day 1	PK: AUC(0-tlast) of LY3502970	Day 1 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24 hours post-dose)
Part B: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-tlast]) of LY3502970 on Day 28	PK: AUC(0-tlast) of LY3502970	Day 28 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 96, 168, 336 hours post-dose)
Part B: PK: Time of Maximum Observed Concentration (Tmax) of LY3502970 on Day 1	PK: Tmax of LY3502970	Day 1 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24 hours post-dose)
Part B: PK: Time of Maximum Observed Concentration (Tmax) of LY3502970 on Day 28	PK: Tmax of LY3502970	Day 28 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 96, 168, 336 hours post-dose)

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

• Ma X, Liu R, Pratt EJ, Benson CT, Bhattachar SN, Sloop KW. Effect of Food Consumption on the Pharmacokinetics, Safety, and Tolerability of Once-Daily Orally Administered Orforglipron (LY3502970), a Non-peptide GLP-1 Receptor Agonist. Diabetes Ther. 2024 Apr;15(4):819-832. doi: 10.1007/s13300-024-01554-1. Epub 2024 Feb 24.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2019
• Primary Completion (Actual): November 2, 2020
• Study Completion (Actual): November 2, 2020

Study Registration Dates

• First Submitted: April 25, 2019
• First Submitted That Met QC Criteria: April 25, 2019
• First Posted (Actual): April 29, 2019

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fatty Acids; Lipids; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Benzazepines; Pyrroles; Heptanoic Acids; Benzodiazepines; Lovastatin; Atorvastatin; Midazolam; Simvastatin; orforglipron
• Other Study ID Numbers: 17416; J2A-MC-GZGA (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