A Phase I, Open-Label, Two-Period, One-Sequence, Crossover Study in Healthy Subjects to Evaluate the Clinical Drug-Drug Interaction of Divarasib With Probe Substrates of P-Glycoprotein (Digoxin) and Breast Cancer Resistance Protein (Rosuvastatin)
Overview
- Phase
- Phase 1
- Intervention
- Digoxin
- Conditions
- Healthy Participants
- Sponsor
- Genentech, Inc.
- Enrollment
- 19
- Locations
- 1
- Primary Endpoint
- Maximum Observed Plasma Concentration (Cmax) of Digoxin and Rosuvastatin
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 1, open-label, two-period, one-sequence, crossover drug-drug interaction study to assess the P-gp and BCRP inhibition potential of divarasib using digoxin and rosuvastatin as probe substrates, respectively, in healthy participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males or females of non-childbearing potential
- •Within body mass index (BMI) range of 18.0 to 32.0 kg/m2, inclusive
Exclusion Criteria
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), neurological, or psychiatric disorder
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator
- •Poor peripheral venous access
Arms & Interventions
Treatment A
Participants will receive a single oral dose of Digoxin and Rosuvastatin drug cocktail.
Intervention: Digoxin
Treatment A
Participants will receive a single oral dose of Digoxin and Rosuvastatin drug cocktail.
Intervention: Rosuvastatin
Treatment B
Participants will receive a single dose of Digoxin and Rosuvastatin drug cocktail administered 2 hours after the Divarasib dose on Day 5.
Intervention: Digoxin
Treatment B
Participants will receive a single dose of Digoxin and Rosuvastatin drug cocktail administered 2 hours after the Divarasib dose on Day 5.
Intervention: Divarasib
Treatment B
Participants will receive a single dose of Digoxin and Rosuvastatin drug cocktail administered 2 hours after the Divarasib dose on Day 5.
Intervention: Rosuvastatin
Outcomes
Primary Outcomes
Maximum Observed Plasma Concentration (Cmax) of Digoxin and Rosuvastatin
Time Frame: Day 1 of Period 1 and Day 5 of Period 2
Area Under the Plasma Concentration-Time Curve from Hour 0 to the Last Measurable Concentration (AUC0-t) of Digoxin and Rosuvastatin
Time Frame: Day 1 of Period 1 and Day 5 of Period 2
Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Digoxin and Rosuvastatin
Time Frame: Day 1 of Period 1 and Day 5 of Period 2
Time to Cmax (Tmax) of Digoxin and Rosuvastatin
Time Frame: Day 1 of Period 1 and Day 5 of Period 2
Secondary Outcomes
- Percentage of Participants with Adverse Events (AEs)(From Day 1 until end of study participation (approximately 2 months))