A PK Study to Assess the Drug-drug Interaction of a BCRP Inhibitor on Adagrasib
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetics - AUC (adagrasib) [Days 1 and 8]
Area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC∞)
- Pharmacokinetics - AUC (adagrasib) [Days 1 and 8]
AUC from time zero to the last quantifiable concentration (AUClast)
- Pharmacokinetics - Cmax (adagrasib) [Days 1 and 8]
Maximum observed plasma concentration (Cmax)
- Pharmacokinetics - Tmax (adagrasib) [Days 1 and 8]
Time to reach Cmax (tmax)
- Pharmacokinetics - t1/2 (adagrasib) [Days 1 and 8]
Elimination half-life (t1/2)
- Pharmacokinetics - CL/F (adagrasib) [Days 1 and 8]
Apparent total plasma clearance (CL/F)
- Pharmacokinetics - Vz/F (adagrasib) [Days 1 and 8]
Apparent volume of distribution (Vz/F)
Secondary Outcome Measures
- Adverse Events (AEs) [Up to 8 weeks from screening]
Incidence and severity of AEs
Eligibility Criteria
Criteria
Inclusion Criteria:
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Males or females, of any race, between 18 and 60 years of age, inclusive, at Screening.
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Body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.
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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.
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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.
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Male subjects must agree to use contraception.
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Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.
Exclusion Criteria:
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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.
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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).
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History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome).
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Significant history or clinical manifestation of any hepatic disease, as determined by laboratory abnormalities.
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History or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study.
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Ventricular dysfunction or history of risk factors for Torsades de Pointes.
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History of drug abuse within 2 years prior to Screening.
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History of alcohol abuse within 12 months prior to Screening.
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Positive serology test results for hepatitis B surface antigen, hepatitis C antibody, and/or human immunodeficiency virus (HIV) 1/2.
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Use of tobacco- or nicotine-containing products within 3 months prior to Check-in.
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Use of any drugs or substances known or suspected to alter drug absorption, distribution, metabolism, or elimination.
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Use or intend to use any prescription medications/products within 14 days prior to Check-in.
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Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations.
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Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days.
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Subjects who, in the opinion of the Investigator, should not participate in this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fortrea Clinical Research Unit Daytona Beach (Labcorp Clinical Research Unit Daytona Beach) | Daytona Beach | Florida | United States | 32117 |
Sponsors and Collaborators
- Mirati Therapeutics Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 849-025