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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
50
Administered orally.
Administered orally.
Administered orally.
Administered orally.
Administered orally.
Administered orally.
Administered orally.
Fortrea Clinical Research Unit Inc.
Daytona Beach, Florida, United States
Fortrea Clinical Research Unit Inc.
Dallas, Texas, United States
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.
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
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).
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
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.
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
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
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
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).
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
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.
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
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.
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
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).
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
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.
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
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
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
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).
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
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.
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
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.
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
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.
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.