A Study of LY3502970 in Healthy Participants

NCT03929744 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17416J2A-MC-GZGA
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Part A: Pharmacokinetics (PK): Maximum Observed Concentration (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

  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

  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

  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

  Day 28 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 96, 168, 336 hours post-dose)

Study Arms (17)

Part A 0.3 mg LY3502970

EXPERIMENTAL

Participants received a single oral dose of 0.3 milligram (mg) LY3502970.

Drug: LY3502970

Part A 1 mg LY3502970

EXPERIMENTAL

Participants received a single oral dose of 1 mg LY3502970.

Drug: LY3502970

Part A 3 mg LY3502970

EXPERIMENTAL

Participants received a single oral dose of 3 mg LY3502970.

Drug: LY3502970

Part A 6 mg LY3502970

EXPERIMENTAL

Participants received a single oral dose of 6 mg LY3502970.

Drug: LY3502970

Part A Placebo

PLACEBO COMPARATOR

Participants received a single oral dose of Placebo.

Drug: Placebo

Part B Placebo

PLACEBO COMPARATOR

Participants received oral doses of placebo once daily for 4 weeks.

Drug: Placebo

Part B: 2 mg LY3502970 (Cohort G)

EXPERIMENTAL

Participants received oral doses of 2 mg LY3502970 once daily for 4 weeks.

Drug: LY3502970

Part B: 2 / 4 / 6 mg LY3502970 (Cohort H)

EXPERIMENTAL

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

Part B: 2 / 4 / 8 / 16 mg LY3502970 (Cohort I)

EXPERIMENTAL

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

Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort J)

EXPERIMENTAL

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: LY3502970; Drug: Atorvastatin; Drug: Midazolam

Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort K)

EXPERIMENTAL

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; Drug: Simvastatin

Part C: 3 mg LY3502970 (Fasted/Fed)

EXPERIMENTAL

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

Part C: 3 mg LY3502970 (Fed/Fasted)

EXPERIMENTAL

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

Part D: 3 mg LY3502970 Prototype Formulation

ACTIVE COMPARATOR

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

Part D: Placebo Prototype Formulation

PLACEBO COMPARATOR

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

Part E: 2 / 5 / 12 / 24 mg LY3502970 (24 mg as Formulation 1)

EXPERIMENTAL

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

Part E: 2 / 5 / 12 / 24 mg LY3502970 (24 mg as Formulation 2)

EXPERIMENTAL

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

Interventions

LY3502970 DRUG

Administered orally.

Part A 0.3 mg LY3502970; Part A 1 mg LY3502970; Part A 3 mg LY3502970; Part A 6 mg LY3502970; Part B: 2 / 4 / 6 mg LY3502970 (Cohort H); Part B: 2 / 4 / 8 / 16 mg LY3502970 (Cohort I); Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort J); Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort K); Part B: 2 mg LY3502970 (Cohort G); Part C: 3 mg LY3502970 (Fasted/Fed); Part C: 3 mg LY3502970 (Fed/Fasted); Part D: 3 mg LY3502970 Prototype Formulation; Part E: 2 / 5 / 12 / 24 mg LY3502970 (24 mg as Formulation 1); Part E: 2 / 5 / 12 / 24 mg LY3502970 (24 mg as Formulation 2)

Placebo DRUG

Administered orally.

Part A Placebo; Part B Placebo; Part D: Placebo Prototype Formulation

Atorvastatin DRUG

Administered orally.

Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort J)

Simvastatin DRUG

Administered orally.

Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort K)

Midazolam DRUG

Administered orally.

Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort J)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Covance Dallas

Dallas, Texas, 75247, United States

Location

Related Publications (1)

• 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.

  PMID: 38402332 DERIVED

MeSH Terms

Interventions

orforglipron; Atorvastatin; Simvastatin; Midazolam

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part C is a crossover design.

Study Record Dates

• First Submitted: April 25, 2019
• First Posted: April 29, 2019
• Study Start: June 12, 2019
• Primary Completion: November 2, 2020
• Study Completion: November 2, 2020
• Last Updated: July 10, 2026
• Results First Posted: July 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)