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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Adults
• Intervention / Treatment: Drug: Adagrasib; Drug: Eltrombopag + adagrasib

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Fortrea Clinical Research Unit Daytona Beach (Labcorp Clinical Research Unit Daytona Beach)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Males or females, of any race, between 18 and 60 years of age, inclusive, at Screening.
2. Body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.
3. 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.
4. 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.
5. Male subjects must agree to use contraception.
6. Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.

Exclusion Criteria:

1. 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.
2. 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).
3. History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome).
4. Significant history or clinical manifestation of any hepatic disease, as determined by laboratory abnormalities.
5. History or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study.
6. Ventricular dysfunction or history of risk factors for Torsades de Pointes.
7. History of drug abuse within 2 years prior to Screening.
8. History of alcohol abuse within 12 months prior to Screening.
9. Positive serology test results for hepatitis B surface antigen, hepatitis C antibody, and/or human immunodeficiency virus (HIV) 1/2.
10. Use of tobacco- or nicotine-containing products within 3 months prior to Check-in.
11. Use of any drugs or substances known or suspected to alter drug absorption, distribution, metabolism, or elimination.
12. Use or intend to use any prescription medications/products within 14 days prior to Check-in.
13. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations.
14. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days.
15. Subjects who, in the opinion of the Investigator, should not participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A; Treatment A: A single oral dose of adagrasib 400 mg (2 × 200-mg tablets) on Day 1;	Drug: Adagrasib; Adagrasib
Active Comparator: Treatment B; 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; Eltrombopag + adagrasib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Incidence and severity of AEs	Up to 8 weeks from screening

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2023
• Primary Completion (Actual): August 9, 2023
• Study Completion (Actual): August 17, 2023

Study Registration Dates

• First Submitted: June 20, 2023
• First Submitted That Met QC Criteria: June 20, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Adagrasib
• Other Study ID Numbers: 849-025

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