A PK Study to Assess the Drug-drug Interaction of a Strong CYP2C8 Inhibitor on Adagrasib

Healthy Adults Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05868356
• Other study ID #: 849-024
• Status: Completed
• Phase: Phase 1
• Start date: June 1, 2023
• Est. completion date: August 7, 2023

Study information

• Verified date: March 2024
• Source: Mirati Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: August 7, 2023
• Est. primary completion date: July 25, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Adults

Intervention

Drug:
• Treatment A
Oral adagrasib 200 mg twice daily (BID) for 8 days (Days 1 to 8). Predose PK blood samples for the measurement of adagrasib concentration will be collected on Days 2 to 7. Serial PK blood samples for adagrasib will be collected up to 12 hours postdose on Days 1 and 8.
• Treatment B
Oral adagrasib 200 mg BID and gemfibrozil 600 mg BID for 10 days (Days 9 to 18), with no evening dose of adagrasib or gemfibrozil on Day 18. Predose PK blood samples for the measurement of adagrasib concentration will be collected on Days 9 to 17 before the morning dose of adagrasib. Predose PK blood samples for the measurement of gemfibrozil trough concentration will be collected on Days 15 to 18 before the morning dose of gemfibrozil. Serial PK blood samples for adagrasib will be collected up to 12 hours postdose on Day 18.

Locations

Country	Name	City	State
United States	Labcorp Clinical Research Unit Inc	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics - AUC (adagrasib)	Area under the plasma concentration time curve (AUC) during a dosage interval (AUCtau)	Days 1, 8, and 18
Primary	Pharmacokinetics - Cmax (adagrasib)	Maximum observed plasma concentration	Days 1, 8, and 18
Primary	Pharmacokinetics - Tmax (adagrasib)	Time to reach Cmax (tmax)	Days 1, 8, and 18
Secondary	Adverse Events (AEs)	Incidence and severity of AEs	Up to 9 weeks from screening