PK Study to Assess Drug-drug Interaction Between Sitravatinib and a P-gp Inducer and an Inhibitor.

Healthy Adults Clinical Trial

Official title:

A Phase 1 Open-label, Two-cohort, One-sequence Crossover Study to Investigator the Effect of P-glycoprotien Inhibitor (Itraconazole) and Inducer (Rifampin) on the Pharmacokinetics, Safety, and Tolerability of Sitravatinib in Health Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05255276
• Other study ID #: 516-013
• Status: Completed
• Phase: Phase 1
• Start date: February 2, 2022
• Est. completion date: February 10, 2023

Study information

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

Clinical Trial Summary

A Phase 1 Open-label, Two-cohort, One-sequence Crossover Study to Investigate the Effect of P glycoprotein Inhibitor (Itraconazole) and Inducer (Rifampin) on the Pharmacokinetics, Safety, and Tolerability of Sitravatinib in Healthy Subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: February 10, 2023
• Est. primary completion date: May 12, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Key Inclusion Criteria:

• Body mass index between 18.0 and 32.0 kg/m2, inclusive.

• In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations at screening and/or check-in, as assessed by the investigator (or qualified designee).

• 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 ICF and to abide by the study restrictions.

Key Exclusion Criteria:

• Significant history of clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, 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 IMP, or other substance (not including seasonal allergies), unless approved by the investigator.

• 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. (Uncomplicated appendectomy and hernia repair are allowed. Cholecystectomy is not allowed.)

• History of Gilbert's syndrome or suspicion of Gilbert's syndrome based on elevated total and indirect bilirubin (may be confirmed by repeat).

• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to study drug administration on Day 1 of Period 1.

Related Conditions & MeSH terms

• Healthy Adults

Intervention

Drug:
• Sitravatinib 50 mg
50 mg Sitravatinib on Day 1 (Group 1A)
• Sitravatinib 100 mg
100 mg Sitravatinib on Day 1 (Group 2A)
• Itraconazole
Itraconazole QD from Day 9 to Day 18, and Sitravatinib 50 mg at Day 12 (Group 1B)
• Rifampin
Rifampin QD from Day 9 to Day 22, and Sitravatinib 100 mg at Day 16 (Group 2B)

Locations

Country	Name	City	State
United States	Labcorp Drug Development Clinical Research Unit	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 - Cmax (sitravatinib)	Maximum observed plasma concentration	Up to Day 168 hours after dosing
Primary	Pharmacokinetics - AUC8 (sitravatinib)	Area under the plasma concentration-time curve from time zero extrapolated to infinity	Up to 168 hours after dosing
Primary	Pharmacokinetics - AUClast (sitravatinib)	Area under the curve from time zero to the last measured time point	Up to 168 hours after dosing
Primary	Pharmacokinetics - tmax (sitravatinib)	Terminal elimination half-life	Up to 168 hours after dosing
Primary	Pharmacokinetics - CL/F (sitravatinib)	Apparent total plasma clearance when dosed orally	Up to 168 hours after dosing
Primary	Pharmacokinetics - Vz/F (sitravatinib)	Apparent volume of distribution when dosed orally	Up to 168 hours after dosing
Primary	Pharmacokinetics - uf (sitravatinib)	Unbound fraction	Up to 168 hours after dosing
Secondary	Adverse Events (AEs)	Incidence and severity of AEs	Up to 12 weeks from screening