A Study to Compare Tablets and Capsules of Orforglipron (LY3502970) in Healthy Participants Who Are Obese or Overweight

NCT06440980 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 18617J2A-MC-GZPI
• Study Type: interventional
• Target: 533
• Locations: 1 country
• Sites: 7

Brief Summary

The main purpose of this study is to see how much of orforglipron (study drug) gets into the bloodstream and how long it takes the body to get rid of it when given as capsules compared to tablets in healthy overweight and obese participants. The safety and tolerability (side effects) of orforglipron when given as capsules and tablets will also be evaluated. The study will be conducted in two parts, with part A and B lasting up to approximately 25 and 22 weeks each respectively, including the screening period.

Conditions

Healthy; Obese; Overweight; Obesity

Keywords

Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Part B: Pharmacokinetics (PK): Steady-state Area Under the Concentration Time Curve From Time Zero to the End of the Dosing Interval, Tau (AUC[0-tau]) of LY3502970 on Day 7

  PK: Area under the concentration versus time curve from time 0 to the end of the once daily dosing interval at steady state AUC\[0-tau\] on Day 7.

  Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16 and 24 hours post-dose on Day 7 for each dosing treatment period (1 period=7 days)

• Part B: PK: Steady-state Maximum Observed Concentration (Cmax) of LY3502970 on Day 7

  PK: Maximum concentration of LY3502970 during a once daily dosing interval at steady state on Day 7.

  Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16 and 24 hours post-dose on Day 7 for each dosing treatment period (1 period=7 days)

Study Arms (14)

Part A: LY3502970 QD Oral Administration (Cohort 1A, Sequence 1)

EXPERIMENTAL

Participants received LY3502970 orally once daily (QD) across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: 1 mg (Capsule) * Period 2: Dose Level 2 (Tablet) * Period 3: Dose Level 1 (Tablet) * Period 4: Dose Level 3 (Tablet) * Period 5: 3 mg (Capsule) * Period 6: Dose Level 5 (Tablet) * Period 7: Dose Level 4 (Tablet) * Period 8: Dose Level 6 (Tablet) * Period 9: 6 mg (Capsule) * Period 10: Dose Level 8 (Tablet) * Period 11: Dose Level 7 (Tablet) * Period 12: Dose Level 9 (Tablet)

Drug: Orforglipron

Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 2)

EXPERIMENTAL

Participants received LY3502970 orally QD across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: Dose Level 2 (Tablet) * Period 2: 1 mg (Capsule) * Period 3: Dose Level 3 (Tablet) * Period 4: Dose Level 1 (Tablet) * Period 5: Dose Level 5 (Tablet) * Period 6: 3 mg (Capsule) * Period 7: Dose Level 6 (Tablet) * Period 8: Dose Level 4 (Tablet) * Period 9: Dose Level 8 (Tablet) * Period 10: 6 mg (Capsule) * Period 11: Dose Level 9 (Tablet) * Period 12: Dose Level 7 (Tablet)

Drug: Orforglipron

Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 3)

EXPERIMENTAL

Participants received LY3502970 orally QD across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: Dose Level 1 (Tablet) * Period 2: Dose Level 3 (Tablet) * Period 3: 1 mg (Capsule) * Period 4: Dose Level 2 (Tablet) * Period 5: Dose Level 4 (Tablet) * Period 6: Dose Level 6 (Tablet) * Period 7: 3 mg (Capsule) * Period 8: Dose Level 5 (Tablet) * Period 9: Dose Level 7 (Tablet) * Period 10: Dose Level 9 (Tablet) * Period 11: 6 mg (Capsule) * Period 12: Dose Level 8 (Tablet)

Drug: Orforglipron

Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 4)

EXPERIMENTAL

Participants received LY3502970 orally QD across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: Dose Level 3 (Tablet) * Period 2: Dose Level 1 (Tablet) * Period 3: Dose Level 2 (Tablet) * Period 4: 1 mg (Capsule) * Period 5: Dose Level 6 (Tablet) * Period 6: Dose Level 4 (Tablet) * Period 7: Dose Level 5 (Tablet) * Period 8: 3 mg (Capsule) * Period 9: Dose Level 9 (Tablet) * Period 10: Dose Level 7 (Tablet) * Period 11: Dose Level 8 (Tablet) * Period 12: 6 mg (Capsule)

Drug: Orforglipron

Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 1)

EXPERIMENTAL

Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: 12 mg (Capsule) * Period 8: Dose Level 11 (Tablet) * Period 9: Dose Level 10 (Tablet) * Period 10: Dose Level 12 (Tablet) * Period 11: 24 mg (Capsule) * Period 12: Dose Level 14 (Tablet) * Period 13: Dose Level 13 (Tablet) * Period 14: Dose Level 16 (Tablet) * Period 15: 36 mg (Capsule) * Period 16: Dose Level 17 (Tablet) * Period 17: Dose Level 15 (Tablet) * Period 18: Dose Level 18 (Tablet)

Drug: Orforglipron

Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 2)

EXPERIMENTAL

Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: Dose Level 11 (Tablet) * Period 8: 12 mg (Capsule) * Period 9: Dose Level 12 (Tablet) * Period 10: Dose Level 10 (Tablet) * Period 11: Dose Level 14 (Tablet) * Period 12: 24 mg (Capsule) * Period 13: Dose Level 16 (Tablet) * Period 14: Dose Level 13 (Tablet) * Period 15: Dose Level 17 (Tablet) * Period 16: 36 mg (Capsule) * Period 17: Dose Level 18 (Tablet) * Period 18: Dose Level 15 (Tablet)

Drug: Orforglipron

Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 3)

EXPERIMENTAL

Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: Dose Level 10 (Tablet) * Period 8: Dose Level 12 (Tablet) * Period 9: 12 mg (Capsule) * Period 10: Dose Level 11 (Tablet) * Period 11: Dose Level 13 (Tablet) * Period 12: Dose Level 16 (Tablet) * Period 13: 24 mg (Capsule) * Period 14: Dose Level 14 (Tablet) * Period 15: Dose Level 15 (Tablet) * Period 16: Dose Level 18 (Tablet) * Period 17: 36 mg (Capsule) * Period 18: Dose Level 17 (Tablet)

Drug: Orforglipron

Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 4)

EXPERIMENTAL

Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: Dose Level 12 (Tablet) * Period 8: Dose Level 10 (Tablet) * Period 9: Dose Level 11 (Tablet) * Period 10: 12 mg (Capsule) * Period 11: Dose Level 16 (Tablet) * Period 12: Dose Level 13 (Tablet) * Period 13: Dose Level 14 (Tablet) * Period 14: 24 mg (Capsule) * Period 15: Dose Level 18 (Tablet) * Period 16: Dose Level 15 (Tablet) * Period 17: Dose Level 17 (Tablet) * Period 18: 36 mg (Capsule)

Drug: Orforglipron

Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 1)

EXPERIMENTAL

Participants received LY3502970 orally QD across inpatient Treatment Periods 1-9 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: 1 mg (Capsule- First Treatment) * Period 2: 1 mg (Capsule- Second Treatment) * Period 3: 0.8 mg (Tablet) * Period 4: 3 mg (Capsule- First Treatment) * Period 5: 3 mg (Capsule- Second Treatment) * Period 6: 2.5 mg (Tablet) * Period 7: 6 mg (Capsule- First Treatment) * Period 8: 6 mg (Capsule- Second Treatment) * Period 9: 5.5 mg (Tablet)

Drug: Orforglipron

Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 2)

EXPERIMENTAL

Participants received LY3502970 orally QD across inpatient Treatment Periods 1-9 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: 1 mg (Capsule- First Treatment) * Period 2: 0.8 mg (Tablet) * Period 3: 1 mg (Capsule- Second Treatment) * Period 4: 3 mg (Capsule- First Treatment) * Period 5: 2.5 mg (Tablet) * Period 6: 3 mg (Capsule- Second Treatment) * Period 7: 6 mg (Capsule- First Treatment) * Period 8: 5.5 mg (Tablet) * Period 9: 6 mg (Capsule- Second Treatment)

Drug: Orforglipron

Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 3)

EXPERIMENTAL

Participants received LY3502970 orally QD across inpatient Treatment Periods 1-9 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: 0.8 mg (Tablet) * Period 2: 1 mg (Capsule- First Treatment) * Period 3: 1 mg (Capsule- Second Treatment) * Period 4: 2.5 mg (Tablet) * Period 5: 3 mg (Capsule- First Treatment) * Period 6: 3 mg (Capsule- Second Treatment) * Period 7: 5.5 mg (Tablet) * Period 8: 6 mg (Capsule- First Treatment) * Period 9: 6 mg (Capsule- Second Treatment)

Drug: Orforglipron

Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 1)

EXPERIMENTAL

Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg \[Capsule\]), followed by inpatient Treatment Periods 7-15 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: 12 mg (Capsule- First Treatment) * Period 8: 12 mg (Capsule- Second Treatment) * Period 9: 9 mg (Tablet) * Period 10: 24 mg (Capsule- First Treatment) * Period 11: 24 mg (Capsule- Second Treatment) * Period 12: 14.5 mg (Tablet) * Period 13: 36 mg (Capsule- First Treatment) * Period 14: 36 mg (Capsule- Second Treatment) * Period 15: 17.2 mg (Tablet)

Drug: Orforglipron

Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 2)

EXPERIMENTAL

Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg \[Capsule\]), followed by inpatient Treatment Periods 7-15 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: 12 mg (Capsule- First Treatment) * Period 8: 9 mg (Tablet) * Period 9: 12 mg (Capsule- Second Treatment) * Period 10: 24 mg (Capsule- First Treatment) * Period 11: 14.5 mg (Tablet) * Period 12: 24 mg (Capsule- Second Treatment) * Period 13: 36 mg (Capsule- First Treatment) * Period 14: 17.2 mg (Tablet) * Period 15: 36 mg (Capsule- Second Treatment)

Drug: Orforglipron

Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 3)

EXPERIMENTAL

Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg \[Capsule\]), followed by inpatient Treatment Periods 7-15 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: 9 mg (Tablet) * Period 8: 12 mg (Capsule- First Treatment) * Period 9: 12 mg (Capsule- Second Treatment) * Period 10: 14.5 mg (Tablet) * Period 11: 24 mg (Capsule- First Treatment) * Period 12: 24 mg (Capsule- Second Treatment) * Period 13: 17.2 mg (Tablet) * Period 14: 36 mg (Capsule- First Treatment) * Period 15: 36 mg (Capsule- Second Treatment)

Drug: Orforglipron

Interventions

Orforglipron DRUG

Administered orally

Also known as: LY3502970

Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 2); Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 3); Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 4); Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 1); Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 2); Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 3); Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 4); Part A: LY3502970 QD Oral Administration (Cohort 1A, Sequence 1); Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 1); Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 2); Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 3); Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 1); Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 2); Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 3)

Eligibility Criteria

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

You may qualify if:

• Participants who are overtly healthy as determined by medical history and physical examination.
• Have a stable body weight for one month prior to screening (less than or equal to 5 percent body weight gain or loss) and Body Mass Index (BMI) in range of 27 to 40 kilogram per meter square (kg/m²).
• Participants must be reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
• Have venous access sufficient to allow for blood sampling.

You may not qualify if:

• Have hemoglobin A1c (HbA1c) level of 6.5 percent (%) or greater.
• Have a history of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders or other significant active, uncontrolled medical conditions.
• Have significant history of or currently have major depressive disorder or psychiatric disorder within the last 2 years.
• Obesity induced by other endocrine disorders, such as Cushing's syndrome or Prader-Willi syndrome.
• Have known clinically significant gastric emptying abnormality.
• Have undergone bariatric surgery (for example: Lap-Band, Gastric Bypass)
• Have a known self or family history (first-degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or any form of thyroid cancer.
• Have an abnormal 12-lead electrocardiogram (ECG) at screening.
• Have history of pancreatitis.
• Judged by the study investigator to be at serious suicidal risk and have answered "Yes" to either question 4 or 5 on the Columbia-Suicide Severity Rating Scale \[C-SSRS\]).
• Have difficulty swallowing capsules or tablets.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (7)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Collaborative Neuroscience Research, LLC

Los Alamitos, California, 90720, United States

Location

Fortrea Clinical Research Unit

Daytona Beach, Florida, 32117, United States

Location

Altasciences Company Inc.

Overland Park, Kansas, 66212, United States

Location

QPS

Springfield, Missouri, 65802, United States

Location

Fortrea Clinical Research Unit

Dallas, Texas, 75247, United States

Location

Fortrea Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

Related Publications (1)

• Ma X, Li YG, Raha S, Sperry DC, Coutant DE, Bhattachar S. Pharmacokinetic Bioequivalence of Orforglipron Tablets and Capsules in Healthy Participants With Obesity or Overweight. Diabetes Obes Metab. 2026 Jul;28(7):5803-5809. doi: 10.1111/dom.70783. Epub 2026 Apr 17.

  PMID: 41994902 DERIVED

Related Links

• A Study to Compare Tablets and Capsules of Orforglipron (LY3502970) in Healthy Participants Who Are Obese or Overweight

MeSH Terms

Conditions

Obesity; Overweight

Interventions

orforglipron

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2024
• First Posted: June 4, 2024
• Study Start: June 24, 2024
• Primary Completion: June 2, 2025
• Study Completion: June 2, 2025
• Last Updated: July 17, 2026
• Results First Posted: July 17, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)