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Completed

NCT Number: NCT06186622

A Drug-Drug Interaction Study of Orforglipron (LY3502970) in Healthy Overweight and Obese Participants

The main purpose of this study is to determine effect of orforglipron capsule formulation on the amount of digoxin, rosuvastatin, acetaminophen, midazolam, and simvastatin (each given alone and together with orforglipron) that enters the bloodstream and how long it takes the body to eliminate them when administered orally in healthy overweight and obese participants. In addition, the effect of the orforglipron tablet on the amount of simvastatin that enters the bloodstream and how long it takes the body to eliminate it will be evaluated.

The study will also assess the effect of sodium bicarbonate when administered alone with simvastatin versus orforglipron capsule containing sodium bicarbonate administered with simvastatin. The safety and tolerability of orforglipron and information about any side effects experienced will be collected.

Study will be conducted in two parts, with part 1 and 2 lasting up to approximately 23 and 24 weeks each, including the screening period.

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Key information

Conditions

Healthy Body Weight Nutrition Disorders Nutritional and Metabolic Diseases Obese Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Fortrea Clinical Research Unit Inc., Daytona Beach, Florida, United States

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants who are overtly healthy as determined by medical history and physical examination.
  • Have body mass index (BMI) equal to or greater than 27 kilograms per meter squared (kg/m²), inclusive, at screening.
  • Have an estimated glomerular filtration rate equal to or greater than 60 milliliters per minute (mL/min).
  • Males and females who agree to follow contraceptive requirements, or women not of childbearing potential (WNOCBP).
  • Have venous access sufficient to allow for blood sampling.

Exclusion criteria

  • Have any type of diabetes with hemoglobin A1c (HbA1c) level of 6.5 percent (%) or greater.
  • 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 significant previous or current history of comorbidities capable of significantly altering the absorption, metabolism, or elimination of drug.
  • Participants must not be currently participating in or completed a clinical trial within the last 90 days.
  • Have a known allergy or hypersensitivity to midazolam, simvastatin, rosuvastatin, or digoxin.

Treatment and study plan

Orforglipron

Drug

Administered orally.

Other names: LY3502970

simvastatin

Drug

Administered orally.

Digoxin

Drug

Administered orally.

Rosuvastatin

Drug

Administered orally.

Acetaminophen

Drug

Administered orally.

midazolam

Drug

Administered orally.

Sodium bicarbonate

Drug

Administered orally.

Primary outcomes

  1. Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)

    Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (h) post-dose; Day 98 (Cohort 1) and Day 93 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose

    AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.

  2. PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)

    Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 104 (Cohort 1) and Day 99 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose

    AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following staggered administration with or without Orforglipron capsule were reported in this outcome measure. Simvastatin was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).

  3. PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)

    Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 7 (Cohort 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose

    AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without sodium bicarbonate administration were reported in this outcome measure.

  4. PK: AUC [0-∞] of Digoxin (Cohort 1 and 2)

    Time frame: Day 2 (For Cohort 1 and 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose ; Day 99 (Cohort 1) and Day 94 (Cohort 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose

  5. PK: AUC [0-∞] of Rosuvastatin (Cohort 1 Only)

    Time frame: Day 8 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose; Day 105 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose

  6. PK: AUC [0-∞] of Acetaminophen (Cohort 1 Only)

    Time frame: Day 10 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 14 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 107 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose

    AUC [0-∞] of acetaminophen following staggered administration with or without either 1 mg or 36 mg Orforglipron capsule were reported in this outcome measure. Acetaminophen was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).

  7. PK: AUC [0-∞] of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only)

    Time frame: Day 12 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose; Day 109 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose

    AUC [0-∞] of midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.

  8. PK: Maximum Observed Concentration (Cmax) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)

    Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 98 (Cohort 1) and Day 93 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose

    Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.

  9. PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)

    Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 104 (Cohort 1) and Day 99 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose

    Cmax of simvastatin and its active acid metabolite (simvastatin acid) following staggered administration with or without Orforglipron capsule were reported in this outcome measure. Simvastatin was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).

  10. PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)

    Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 7 (Cohort 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose

    Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without sodium bicarbonate administration were reported in this outcome measure.

  11. PK: Cmax of Digoxin (Cohorts 1 and 2)

    Time frame: Day 2 (For Cohort 1 and 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose; Day 99 (Cohort 1) and Day 94 (Cohort 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose

  12. PK: Cmax of Rosuvastatin (Cohort 1 Only)

    Time frame: Day 8 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose; Day 105 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose

  13. PK: Cmax of Acetaminophen (Cohort 1 Only)

    Time frame: Day 10 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 14 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 107 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose

    Cmax of acetaminophen following staggered administration with or without either 1 mg or 36 mg Orforglipron capsule were reported in this outcome measure. Acetaminophen was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).

  14. PK: Cmax of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only)

    Time frame: Day 12 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose; Day 109 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose

    Cmax of Midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule is reported in this outcome measure.

Secondary outcomes

  1. PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2)

    Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 111 (Cohort 1) and Day 101 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose

    AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron tablet were reported in this outcome measure.

  2. PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2)

    Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 111 (Cohort 1) and Day 101 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose

    Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron tablet were reported in this outcome measure.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

A Drug-Drug Interaction Study to Assess the Effect of Orforglipron on the Pharmacokinetics of Digoxin, Simvastatin, Rosuvastatin, Acetaminophen, and Midazolam in Healthy Overweight and Obese Participants

Important dates

Study start
2024
Primary completion
2024
Study completion
2024
First posted
Jan 2, 2024
Registry last updated
May 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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