A Drug-Drug Interaction Study of Orforglipron (LY3502970)... | NCT06186622 | Trialant
NCT06186622
Sponsor
Eli Lilly and Company
Status
Completed
Last Update Posted
May 22, 2026Actual
Enrollment
50Actual
Phase
Phase 1
Conditions
Healthy
Obese
Overweight
Interventions
Orforglipron
Simvastatin
Digoxin
Rosuvastatin
Acetaminophen
Midazolam
Sodium Bicarbonate
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT06186622
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
18631
Secondary IDs
ID
Type
Description
Link
J2A-MC-GZPG
Other Identifier
Eli Lilly and Company
Brief Title
A Drug-Drug Interaction Study of Orforglipron (LY3502970) in Healthy Overweight and Obese Participants
Official 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
Acronym
Not provided
Organization
Eli Lilly and CompanyINDUSTRY
Status Module
Record Verification Date
Apr 2026
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 2, 2024Actual
Primary Completion Date
Jul 10, 2024Actual
Completion Date
Jul 10, 2024Actual
First Submitted Date
Dec 16, 2023
First Submission Date that Met QC Criteria
Dec 16, 2023
First Posted Date
Jan 2, 2024Actual
Results Waived
Not provided
Results First Submitted Date
Apr 29, 2026
Results First Submitted that Met QC Criteria
Apr 29, 2026
Results First Posted Date
May 22, 2026Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Apr 29, 2026
Last Update Posted Date
May 22, 2026Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Eli Lilly and CompanyINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
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.
Detailed Description
Not provided
Conditions Module
Conditions
Healthy
Obese
Overweight
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
50Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration
Experimental
Participants received single oral doses as follows:Day 1: 20 milligram(mg) simvastatin; Day 2: 0.25 mg digoxin; Day 7:20 mg simvastatin + 600 mg sodium bicarbonate; Day 8: 20 mg rosuvastatin; Day 10: 1000 mg acetaminophen; Day 12: 0.2 mg midazolam;Day 14: 1 mg Orforglipron, followed by 1000 mg acetaminophen administered 2 hours (±10 minutes) later (staggered); Day 15: 1 mg Orforglipron; Days 16-97: Orforglipron administered once daily with dose escalation every 14 days:1 mg (Days 16-27), 3 mg (Days 28-41),6 mg (Days 42-55),12 mg (Days 56-69),24 mg (Days 70-83),36 mg (Days 84-97).
Days 98-110: 36 mg Orforglipron administered once daily with co administration as follows:Day 98: 20 mg simvastatin (simultaneous); Day 99: 0.25 mg digoxin (simultaneous); Day 104: 20 mg simvastatin (staggered); Day 105:20 mg rosuvastatin (simultaneous); Day 107: 1000 mg acetaminophen (staggered); Day 109:0.2 mg midazolam (simultaneous); Day 111: 20 mg Orforglipron tablet + 20 mg simvastatin (simultaneous).
Drug: Orforglipron
Drug: Simvastatin
Drug: Digoxin
Drug: Rosuvastatin
Drug: Acetaminophen
Drug: Midazolam
Drug: Sodium Bicarbonate
Cohort 2: Oral Drug Dosing With or Without Orforglipron Co-Administration
Experimental
Participants received single oral doses as follows: Day 1: 20 mg Simvastatin; Day 2: 0.25 mg Digoxin; Day 7: 20 mg Simvastatin + 600 mg Sodium Bicarbonate; Day 9: 1 mg Orforglipron capsule; Days 10-90: Participants received orforglipron capsule orally QD for 12 weeks, beginning at 1 mg QD. The dose was escalated every 14 days as follows: 1 mg (Days 10-22), 3 mg (Days 23-36), 6 mg (Days 37-50), 12 mg (Days 51-64), 24 mg (Days 65-78), and 36 mg (Days 79-90).
Participants continued 36 mg Orforglipron QD until Day 100, with co-administration of the following drugs; Day 93: 20 mg Simvastatin (simultaneous); Day 94: 0.25 mg Digoxin (simultaneous); Day 99: 20 mg Simvastatin administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing); Day 101: 20 mg Orforglipron tablet + 20 mg Simvastatin (simultaneous)
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Orforglipron
Drug
Administered orally.
Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration
Cohort 2: Oral Drug Dosing With or Without Orforglipron Co-Administration
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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)
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.
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
PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
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).
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
PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)
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.
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
PK: AUC [0-∞] of Digoxin (Cohort 1 and 2)
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
Secondary Outcomes
Measure
Description
Time Frame
PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2)
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.
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
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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.
Accepts Healthy Volunteers
Yes
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
70 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
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
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Fortrea Clinical Research Unit Inc.
Daytona Beach
Florida
32117
United States
Fortrea Clinical Research Unit Inc.
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration
Participants received single oral doses of the following drugs:
Day 1: 20 milligram (mg) Simvastatin alone
Day 2: 0.25 mg Digoxin alone
Day 7: 20 mg Simvastatin + 600 mg Sodium Bicarbonate
Day 8: 20 mg Rosuvastatin alone
Day 10: 1000 mg Acetaminophen alone
Day 12: 0.2 mg Midazolam alone
Day 14: 1 mg Orforglipron capsule + 1000 mg Acetaminophen administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing)
Day 15: 1 mg Orforglipron capsule
Days 16-97: Participants received Orforglipron capsule orally once daily (QD) for 12 weeks, beginning at 1 mg QD. The dose was escalated every 14 days as follows: 1 mg (Days 16-27), 3 mg (Days 28-41), 6 mg (Days 42-55), 12 mg (Days 56-69), 24 mg (Days 70-83), and 36 mg (Days 84-97).
Participants continued 36 mg Orforglipron QD until Day 110, with co-administration of the following drugs:
Day 98: 20 mg Simvastatin (simultaneous dosing)
Day 99: 0.25 mg Digoxin (simultaneous dosing)
Day 104: 20 mg Simvastatin administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing)
Day 105: 20 mg Rosuvastatin (simultaneous dosing)
Day 107: 1000 mg Acetaminophen administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing)
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).
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
PK: AUC [0-∞] of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only)
AUC [0-∞] of midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
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
PK: Maximum Observed Concentration (Cmax) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
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
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
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).
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
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)
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.
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
PK: Cmax of Digoxin (Cohorts 1 and 2)
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
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).
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
PK: Cmax of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only)
Cmax of Midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule is reported in this outcome measure.
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
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2)
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron tablet were reported in this outcome measure.
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
Dallas
Texas
75247
United States
FG001
Cohort 2: Oral Drug Dosing With or Without Orforglipron Co-Administration
Participants received single oral doses of the following drugs:
Day 1: 20 milligram (mg) Simvastatin alone
Day 2: 0.25 mg Digoxin alone
Day 7: 20 mg Simvastatin + 600 mg Sodium Bicarbonate
Day 9: 1 mg Orforglipron capsule
Days 10-90: Participants received orforglipron capsule orally QD for 12 weeks, beginning at 1 mg QD. The dose was escalated every 14 days as follows: 1 mg (Days 10-22), 3 mg (Days 23-36), 6 mg (Days 37-50), 12 mg (Days 51-64), 24 mg (Days 65-78), and 36 mg (Days 79-90).
Participants continued 36 mg Orforglipron QD until Day 100, with co-administration of the following drugs:
Day 93: 20 mg Simvastatin (simultaneous dosing)
Day 94: 0.25 mg Digoxin (simultaneous dosing)
Day 99: 20 mg Simvastatin administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing)
Safety Analysis Population (Received at Least One Dose of Study Drug)
FG00030 subjectsIn Cohort 1, 30 participants started on Days 1-2 (n=30). Discontinuations occurred as follows: 2 after digoxin (Day 2; n=28), 1 after rosuvastatin (Day 8; n=27), 1 after 1 mg orforglipron (Day 27; n=26), and 4 during 36 mg orforglipron dosing (Days 93-97; n=22). Of the 22 remaining participants in the co-administration period (Days 98-111), 1 did not receive orforglipron or midazolam on Day 109 due to intolerability (n=21) but resumed dosing on Day 110 per protocol.
FG00120 subjectsIn Cohort 2, 20 participants were included during Days 1-36 (n=20). After 1 discontinuation on Day 34 following 3 mg Orforglipron administration, 19 participants remained during Days 37-64 (n=19). One participant discontinued on Day 57 after 12 mg orforglipron, leaving 18 participants during Days 65-92 (n=18). Two participants discontinued on Day 90 after 36 mg Orforglipron, leaving 16 participants during Days 93-101 (n=16).
COMPLETED
FG00022 subjects
FG00116 subjects
NOT COMPLETED
FG0008 subjects
FG0014 subjects
Type
Comment
Reasons
Adverse Event
FG0006 subjects
FG0011 subjects
Sponsor Decision
FG0000 subjects
FG0012 subjects
Protocol Violation
FG0001 subjects
FG0010 subjects
Withdrawal by Subject
FG0001 subjects
FG0011 subjects
All enrolled population.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1: Oral Drug Dosing With or Without Orforglipron
Participants received single oral doses of the following drugs:
Day 1: 20 milligram (mg) Simvastatin alone
Day 2: 0.25 mg Digoxin alone
Day 7: 20 mg Simvastatin + 600 mg Sodium Bicarbonate
Day 8: 20 mg Rosuvastatin alone
Day 10: 1000 mg Acetaminophen alone
Day 12: 0.2 mg Midazolam alone
Day 14: 1 mg Orforglipron capsule + 1000 mg Acetaminophen administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing)
Day 15: 1 mg Orforglipron capsule
Days 16-97: Participants received Orforglipron capsule orally once daily (QD) for 12 weeks, beginning at 1 mg QD. The dose was escalated every 14 days as follows: 1 mg (Days 16-27), 3 mg (Days 28-41), 6 mg (Days 42-55), 12 mg (Days 56-69), 24 mg (Days 70-83), and 36 mg (Days 84-97).
Participants continued 36 mg Orforglipron QD until Day 110, with co-administration of the following drugs:
Day 98: 20 mg Simvastatin (simultaneous dosing)
Day 99: 0.25 mg Digoxin (simultaneous dosing)
Day 104: 20 mg Simvastatin administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing)
Day 105: 20 mg Rosuvastatin (simultaneous dosing)
Day 107: 1000 mg Acetaminophen administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing)
Cohort 2: Oral Drug Dosing With or Without Orforglipron
Participants received single oral doses of the following drugs:
Day 1: 20 mg Simvastatin alone
Day 2: 0.25 mg Digoxin alone
Day 7: 20 mg Simvastatin + 600 mg Sodium Bicarbonate
Day 9: 1 mg Orforglipron capsule
Days 10-90: Participants received Orforglipron capsule orally QD for 12 weeks, beginning at 1 mg QD. The dose was escalated every 14 days as follows: 1 mg (Days 10-22), 3 mg (Days 23-36), 6 mg (Days 37-50), 12 mg (Days 51-64), 24 mg (Days 65-78), and 36 mg (Days 79-90).
Participants continued 36 mg Orforglipron QD until Day 100, with co-administration of the following drugs:
Day 93: 20 mg Simvastatin (simultaneous dosing)
Day 94: 0.25 mg Digoxin (simultaneous dosing)
Day 99: 20 mg Simvastatin administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing)
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)
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.
All participants who received at least 1 dose of study drug and had evaluable PK data for this specific outcome. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
Nanogram* hours per milliliter (ng*h/ml)
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
ID
Title
Description
OG000
20 mg Simvastatin Alone
Participants received single dose of 20 mg simvastatin alone orally on Day 1 (Cohorts 1 and 2).
Participants received simultaneous dosing of 20 mg simvastatin and 36 mg Orforglipron capsule orally on Day 98 (Cohort 1) and Day 93 (Cohort 2).
Units
Counts
Participants
OG00050
OG00136
Title
Denominators
Categories
Simvastatin
ParticipantsOG00050
ParticipantsOG00136
Title
Measurements
OG00022.1± 79.2
Primary
PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
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).
All participants who received at least 1 dose of study drug and had evaluable PK data. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/ml
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
ID
Title
Description
OG000
20 mg Simvastatin Alone
Participants received single dose of 20 mg simvastatin alone orally on Day 1 (Cohorts 1 and 2)
Participants received staggered dosing of 36 mg Orforglipron capsule followed by 20 mg Simvastatin orally on Day 104 (Cohort 1) and Day 99 (Cohort 2).
Primary
PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)
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.
All participants who received at least 1 dose of study drug and had evaluable PK data for this specific outcome. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/ml
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
ID
Title
Description
OG000
20 mg Simvastatin Alone
Participants received single dose of 20 mg simvastatin alone orally on Day 1 (Cohorts 1 and 2).
Participants received simultaneous dosing of 20 mg simvastatin and 600 mg sodium bicarbonate orally on Day 7 (Cohorts 1 and 2).
Primary
PK: AUC [0-∞] of Digoxin (Cohort 1 and 2)
All participants who received at least 1 dose of study drug and had evaluable PK data for this specific outcome. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/ml
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
ID
Title
Description
OG000
0.25 mg Digoxin Alone
Participants received 0.25 mg digoxin alone on Day 2 (Cohort 1 and 2).
Participants received simultaneous dosing of 20 mg rosuvastatin and 36 mg Orforglipron capsule orally on Day 105 (Cohort 1 only).
Units
Counts
Participants
OG000
Primary
PK: AUC [0-∞] of Acetaminophen (Cohort 1 Only)
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).
All participants who received at least 1 dose of study drug and had evaluable PK data.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/ml
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
ID
Title
Description
OG000
1000 mg Acetaminophen Alone
Participants received single dose of 1000 mg acetaminophen alone orally on Day 10 (Cohort 1 only).
Participants received staggered dosing of 36 mg single dose of Orforglipron capsule followed by 1000 mg acetaminophen orally on Day 107 (Cohort 1 Only).
Primary
PK: AUC [0-∞] of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only)
AUC [0-∞] of midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
All participants who received at least 1 dose of study drug and had evaluable PK data.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/ml
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
ID
Title
Description
OG000
0.2 mg Midazolam Alone
Participants received single dose of 0.2 mg midazolam alone orally on Day 12 (Cohort 1 only)
Participants received simultaneous dosing of 0.2 mg midazolam and 36 mg Orforglipron capsule orally on Day 109 (Cohort 1 Only).
Units
Counts
Participants
Primary
PK: Maximum Observed Concentration (Cmax) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
All participants who received at least 1 dose of study drug and had evaluable PK data. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
Nanogram per milliliter (ng/ml)
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
ID
Title
Description
OG000
20 mg Simvastatin Alone
Participants received single dose of 20 mg simvastatin alone orally on Day 1 (Cohort 1 and 2)
Participants received simultaneous dosing of 20 mg simvastatin and 36 mg Orforglipron capsule orally on Day 98 (Cohort 1) and Day 93 (Cohort 2).
Primary
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
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).
All participants who received at least 1 dose of study drug and had evaluable PK data. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/ml
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
ID
Title
Description
OG000
20 mg Simvastatin Alone
Participants received single dose of 20 mg simvastatin alone orally on Day 1 (Cohort 1 and 2).
Participants received staggered dosing of 36 mg Orforglipron capsule followed by 20 mg Simvastatin orally on Day 104 (Cohort 1) and Day 99 (Cohort 2).
Primary
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)
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.
All participants who received at least 1 dose of study drug and had evaluable PK data. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/ml
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
ID
Title
Description
OG000
20 mg Simvastatin Alone
Participants received single dose of 20 mg simvastatin alone orally on Day 1 (Cohort 1 and 2).
Participants received simultaneous dosing of 20 mg simvastatin and 600 mg sodium bicarbonate orally on Day 7 (Cohorts 1 and 2).
Primary
PK: Cmax of Digoxin (Cohorts 1 and 2)
All participants who received at least 1 dose of study drug and had evaluable PK data. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/ml
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
ID
Title
Description
OG000
0.25 mg Digoxin Alone
Participants received 0.25 mg digoxin alone on Day 2 (Cohort 1 and 2).
Participants received simultaneous dosing of 20 mg rosuvastatin and 36 mg Orforglipron capsule orally on Day 105 (Cohort 1 only).
Units
Counts
Participants
OG000
Primary
PK: Cmax of Acetaminophen (Cohort 1 Only)
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).
All participants who received at least 1 dose of study drug and had evaluable PK data.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/ml
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
ID
Title
Description
OG000
1000 mg Acetaminophen Alone
Participants received single dose of 1000 mg acetaminophen alone orally on Day 10 (Cohort 1 only)
Participants received staggered dosing of 36 mg single dose of Orforglipron capsule followed by 1000 mg acetaminophen orally on Day 107 (Cohort 1 only).
Primary
PK: Cmax of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only)
Cmax of Midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule is reported in this outcome measure.
All participants who received at least 1 dose of study drug and had evaluable PK data.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/ml
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
ID
Title
Description
OG000
0.2 mg Midazolam Alone
Participants received single dose of 0.2 mg midazolam alone orally on Day 12 (Cohort 1 only).
Participants received simultaneous dosing of 0.2 mg midazolam and 36 mg Orforglipron capsule orally on Day 109 (Cohort 1 only).
Units
Counts
Participants
Secondary
PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2)
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.
All participants who received at least 1 dose of study drug and had evaluable PK data. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/ml
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
ID
Title
Description
OG000
20 mg Simvastatin Alone
Participants received single dose of 20 mg simvastatin alone orally on Day 1 (Cohorts 1 and 2).
Participants received simultaneous dosing of 20 mg simvastatin and 20 mg Orforglipron tablet orally on Day 111 (Cohort 1) and Day 101 (Cohort 2).
Secondary
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2)
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron tablet were reported in this outcome measure.
All participants who received at least 1 dose of study drug and had evaluable PK data. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/ml
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
ID
Title
Description
OG000
20 mg Simvastatin Alone
Participants received single dose of 20 mg simvastatin alone orally on Day 1 (Cohorts 1 and 2).
Participants received simultaneous dosing of 20 mg simvastatin and 20 mg Orforglipron tablet orally on Day 111 (Cohort 1) and Day 101 (Cohort 2).
Time Frame
Cohort 1: Baseline up to end of follow-up (up to 129 days); Cohort 2: Baseline up to end of follow-up (up to 119 days)
Description
All participants who received at least 1 dose of study drug (Orforglipron, Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, and Midazolam). Participants were analyzed according to the treatment regimen they received.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cohort 1: 20 mg Simvastatin Alone (Day 1)
Participants received single dose of 20 mg simvastatin alone orally on Day 1.
0
30
0
30
2
30
EG001
Cohort 1: 0.25 mg Digoxin Alone (Day 2)
Participants received 0.25 mg digoxin alone on Day 2.