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

Study Overview
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Brief Summary
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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

Official Title
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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
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Healthy Adults

Intervention / Treatment
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* Drug: Adagrasib
* Drug: Eltrombopag + adagrasib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: One-sequence Crossover Study
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |