A PK Study to Assess the Drug-drug Interaction of a BCRP Inhibitor on Adagrasib

NCT05924152 | Completed Phase 1 FDA Drug

• 1 other identifier: 849-025
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1, Open-label, One-sequence Crossover Study to Investigate the Effect of a Breast Cancer Resistance Protein Inhibitor on the Single-dose Pharmacokinetics of Adagrasib in Healthy Adult Subjects

Conditions

Healthy Adults

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetics - AUC (adagrasib)

  Area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC∞)

  Days 1 and 8

• Pharmacokinetics - AUC (adagrasib)

  AUC from time zero to the last quantifiable concentration (AUClast)

  Days 1 and 8

• Pharmacokinetics - Cmax (adagrasib)

  Maximum observed plasma concentration (Cmax)

  Days 1 and 8

• Pharmacokinetics - Tmax (adagrasib)

  Time to reach Cmax (tmax)

  Days 1 and 8

• Pharmacokinetics - t1/2 (adagrasib)

  Elimination half-life (t1/2)

  Days 1 and 8

• Pharmacokinetics - CL/F (adagrasib)

  Apparent total plasma clearance (CL/F)

  Days 1 and 8

• Pharmacokinetics - Vz/F (adagrasib)

  Apparent volume of distribution (Vz/F)

  Days 1 and 8

Secondary Outcomes (1)

• Adverse Events (AEs)

  Up to 8 weeks from screening

Study Arms (2)

Treatment A

ACTIVE COMPARATOR

Treatment A: A single oral dose of adagrasib 400 mg (2 × 200-mg tablets) on Day 1;

Drug: Adagrasib

Treatment B

ACTIVE COMPARATOR

Treatment B: A single oral dose of eltrombopag 75 mg (1 × 75-mg tablet) plus adagrasib 400 mg (2 × 200-mg tablets) on Day 8.

Drug: Eltrombopag + adagrasib

Interventions

Adagrasib DRUG

Adagrasib

Treatment A

Eltrombopag + adagrasib DRUG

Eltrombopag + adagrasib

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 any race, between 18 and 60 years of age, inclusive, at Screening.
• Body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, or clinical laboratory evaluations at Screening and Check-in as assessed by the Investigator.
• Females of childbearing potential will not be pregnant or lactating and must have a negative result on an approved pregnancy test at Screening and Check-in. Females of childbearing potential must agree to use contraception.
• Male subjects must agree to use contraception.
• Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.

You may not qualify if:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, thrombotic, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, any components of the investigational product (IP), or other substance (not including seasonal allergies).
• History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome).
• Significant history or clinical manifestation of any hepatic disease, as determined by laboratory abnormalities.
• History or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study.
• Ventricular dysfunction or history of risk factors for Torsades de Pointes.
• History of drug abuse within 2 years prior to Screening.
• History of alcohol abuse within 12 months prior to Screening.
• Positive serology test results for hepatitis B surface antigen, hepatitis C antibody, and/or human immunodeficiency virus (HIV) 1/2.
• Use of tobacco- or nicotine-containing products within 3 months prior to Check-in.
• Use of any drugs or substances known or suspected to alter drug absorption, distribution, metabolism, or elimination.
• Use or intend to use any prescription medications/products within 14 days prior to Check-in.
• Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations.
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days.
• Subjects who, in the opinion of the Investigator, should not participate in this study.

Sponsors & Collaborators

• Mirati Therapeutics Inc.: lead

Study Sites (1)

Fortrea Clinical Research Unit Daytona Beach (Labcorp Clinical Research Unit Daytona Beach)

Daytona Beach, Florida, 32117, United States

Location

MeSH Terms

Interventions

adagrasib; eltrombopag

Study Design

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

Model Details: One-sequence Crossover Study

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: June 29, 2023
• Study Start: June 29, 2023
• Primary Completion: August 9, 2023
• Study Completion: August 17, 2023
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)