Clinical trial NCT05868356: A PK Study to Assess the Drug-drug Interaction of a Strong CYP2C8 Inhibitor on Adagrasib
Official title: A Phase 1, Open-label, Multiple-dose, One-sequence Crossover Study to Investigate the Effect of Repeated Oral Doses of a Strong CYP2C8 Inhibitor on the Steady-state Pharmacokinetics of Adagrasib in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adults
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-05-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A Phase 1, Open-label, Multiple-dose, One-sequence Crossover Study to Investigate the Effect of Repeated Oral Doses of a Strong CYP2C8 Inhibitor on the Steady-state Pharmacokinetics of Adagrasib in Healthy Adult Subjects
Primary purpose: OTHER

Brief summary: A Phase 1, Open-label, Multiple-dose, One-sequence Crossover Study to Investigate the Effect of Repeated Oral Doses of a Strong CYP2C8 Inhibitor on the Steady-state Pharmacokinetics of Adagrasib in Healthy Adult Subjects


Eligibility criteria: 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, 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) likely to alter absorption of study treatment or result in inability to swallow oral medications.
4. Significant history or clinical manifestation of any hepatic disease.
5. History or current diagnosis of uncontrolled or significant cardiac disease.
6. Ventricular dysfunction or history of risk factors for Torsades de Pointes.
7. History of allergic reaction to fibric acid derivatives.
8. History of drug abuse within 2 years prior to Screening.
9. History of alcohol abuse within 12 months prior to Screening.
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. Use or intend to use slow-release medications/products considered to still be active within 14 days prior to Check-in.
15. Participation in a clinical study involving administration of an investigational drug in the past 30 days or 5 half-lives prior to dosing, whichever is longer.
16. Have previously completed or withdrawn from this study or any other study investigating adagrasib, and have previously received the IP.
17. Receipt of blood products within 3 months prior to Check-in.
18. Donation of blood from 56 days prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
19. Subjects who, in the opinion of the Investigator, should not participate in this study.

Primary outcomes:
measure: Pharmacokinetics - AUC (adagrasib)
timeFrame: Days 1, 8, and 18
measure: Pharmacokinetics - Cmax (adagrasib)
timeFrame: Days 1, 8, and 18
measure: Pharmacokinetics - Tmax (adagrasib)
timeFrame: Days 1, 8, and 18
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: Up to 9 weeks from screening
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Labcorp Clinical Research Unit Inc
state: Texas
Study officials:
References: