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

NCT06677957 | Completed Phase 1 FDA Drug

• 1 other identifier: GP45712
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Percentage of Participants with Adverse Events (AEs)

  From Day 1 until end of study participation (approximately 2 months)

Study Arms (2)

Treatment A

EXPERIMENTAL

Participants will receive a single oral dose of Digoxin and Rosuvastatin drug cocktail.

Drug: Digoxin; Drug: Rosuvastatin

Treatment B

EXPERIMENTAL

Participants will receive a single dose of Digoxin and Rosuvastatin drug cocktail administered 2 hours after the Divarasib dose on Day 5.

Drug: Digoxin; Drug: Divarasib; Drug: Rosuvastatin

Interventions

Digoxin DRUG

Digoxin will be administered together with Rosuvastatin as a drug cocktail as specified for the respective period

Treatment A; Treatment B

Divarasib DRUG

Divarasib will be administered in combination with Digoxin and Rosuvastatin as specified for the respective period

Treatment B

Rosuvastatin DRUG

Rosuvastatin will be administered together with Digoxin as a drug cocktail as specified for the respective period

Treatment A; Treatment B

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females of non-childbearing potential
• Within body mass index (BMI) range of 18.0 to 32.0 kg/m2, inclusive

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

Daytona Beach Clinical Rsch Unit

Daytona Beach, Florida, 32117, United States

Location

MeSH Terms

Interventions

Digoxin; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 7, 2024
• Study Start: November 6, 2024
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: January 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)