A Clinical Trial to Investigate the Clinical Drug-Drug Interaction of Divarasib With Probe Substrates of P-Glycoprotein and Breast Cancer Resistance Protein in Healthy Participants

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)

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Digoxin; Drug: Divarasib; Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Daytona Beach Clinical Rsch Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Participants will receive a single oral dose of Digoxin and Rosuvastatin drug cocktail.	Drug: Digoxin; Digoxin will be administered together with Rosuvastatin as a drug cocktail as specified for the respective period; Drug: Rosuvastatin; Rosuvastatin will be administered together with Digoxin as a drug cocktail as specified for the respective period
Experimental: Treatment B; Participants will receive a single dose of Digoxin and Rosuvastatin drug cocktail administered 2 hours after the Divarasib dose on Day 5.	Drug: Digoxin; Digoxin will be administered together with Rosuvastatin as a drug cocktail as specified for the respective period; Drug: Divarasib; Divarasib will be administered in combination with Digoxin and Rosuvastatin as specified for the respective period; Drug: Rosuvastatin; Rosuvastatin will be administered together with Digoxin as a drug cocktail as specified for the respective period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Digoxin and Rosuvastatin	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	Day 1 of Period 1 and Day 5 of Period 2
Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Digoxin and Rosuvastatin	Day 1 of Period 1 and Day 5 of Period 2
Time to Cmax (Tmax) of Digoxin and Rosuvastatin	Day 1 of Period 1 and Day 5 of Period 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events (AEs)	From Day 1 until end of study participation (approximately 2 months)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2024
• Primary Completion (Actual): December 30, 2024
• Study Completion (Actual): December 30, 2024

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Actual): November 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anti-Arrhythmia Agents; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Digoxin
• Other Study ID Numbers: GP45712

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No