Healthy, Obese, Overweight
Conditions
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.
Interventions
DRUGOrforglipron
Administered orally.
DRUGSimvastatin
Administered orally.
DRUGDigoxin
Administered orally.
DRUGRosuvastatin
Administered orally.
DRUGAcetaminophen
Administered orally.
DRUGMidazolam
Administered orally.
DRUGSodium Bicarbonate
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
| PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2) | 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). |
| PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2) | 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. |
| 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 | — |
| PK: AUC [0-∞] of Rosuvastatin (Cohort 1 Only) | 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 | — |
| PK: AUC [0-∞] of Acetaminophen (Cohort 1 Only) | 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). |
| PK: AUC [0-∞] of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only) | 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. |
| PK: Maximum Observed Concentration (Cmax) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2) | 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. |
| PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2) | 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). |
| PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2) | 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. |
| 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 | — |
| PK: Cmax of Rosuvastatin (Cohort 1 Only) | 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 | — |
| PK: Cmax of Acetaminophen (Cohort 1 Only) | 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). |
| PK: Cmax of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only) | 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
| Measure | Time frame | Description |
|---|---|---|
| PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2) | 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. |
| PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2) | 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. |
Countries
United States
Contacts
STUDY_DIRECTORCall 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
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 42.9 Years STANDARD_DEVIATION 12.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Region of Enrollment United States | 50 Participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk | EG026 affected / at risk | EG027 affected / at risk | EG028 affected / at risk | EG029 affected / at risk | EG030 affected / at risk | EG031 affected / at risk | EG032 affected / at risk | EG033 affected / at risk | EG034 affected / at risk | EG035 affected / at risk | EG036 affected / at risk | EG037 affected / at risk | EG038 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 | 0 / 28 | 0 / 28 | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 26 | 0 / 26 | 0 / 26 | 0 / 26 | 0 / 26 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 21 | 0 / 22 | 0 / 22 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 19 | 0 / 19 | 0 / 18 | 0 / 18 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 2 / 30 | 0 / 30 | 0 / 28 | 0 / 28 | 1 / 27 | 0 / 27 | 1 / 27 | 4 / 27 | 2 / 26 | 5 / 26 | 2 / 26 | 2 / 26 | 11 / 26 | 0 / 22 | 2 / 22 | 2 / 22 | 0 / 22 | 2 / 22 | 2 / 22 | 1 / 22 | 1 / 22 | 1 / 21 | 0 / 22 | 2 / 22 | 1 / 20 | 0 / 20 | 0 / 20 | 9 / 20 | 7 / 20 | 6 / 19 | 6 / 19 | 4 / 18 | 10 / 18 | 1 / 16 | 1 / 16 | 2 / 16 | 1 / 16 | 0 / 16 | 3 / 16 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 28 | 0 / 28 | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 26 | 0 / 26 | 0 / 26 | 0 / 26 | 0 / 26 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 21 | 0 / 22 | 0 / 22 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 19 | 1 / 19 | 0 / 18 | 0 / 18 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
None listed