PK Study to Assess Drug-drug Interaction Between Sitravatinib and a P-gp Inducer and an Inhibitor.
Phase 1
Completed
- Conditions
- Healthy Adults
- Interventions
- Registration Number
- NCT05255276
- Lead Sponsor
- Mirati Therapeutics Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Group 1 Treatment A Sitravatinib 50 mg A single-dose administration of sitravatinib malate 50 mg on Day 1. Day 12, a single dose of sitravatinib malate 50 mg will be will be followed by a 72-hour PK sample collection period. Subjects will be discharged from the CRU on Day 4 after collection of 72-hour postdose PK sample and completion of all required study procedures. Group 2 Treatment A Sitravatinib 100 mg A single-dose administration of sitravatinib malate 100 mg on Day 1 will be followed by a 72-hour PK sample collection period. Subjects will be discharged from the CRU on Day 4 after collection of 72-hour postdose PK sample and completion of all required study procedures. Group 1 Treatment B Itraconazole On Days 9 to 11, itraconazole 200 mg will be administered QD in the morning. On Day 12, a single dose of sitravatinib malate 50 mg will be coadministered with itraconazole. Itraconazole QD dosing will continue on Days 13 to 18 to maintain steady state during the PK sample collection period. Group 2 Treatment B Rifampin On Days 9 to 15, rifampin 600 mg will be administered QD in the morning. On Day 16, a single dose of sitravatinib malate 100 mg will be coadministered with rifampin followed by a 72 hour PK sample collection period. Rifampin QD dosing will continue on Days 17 to 22 to maintain steady state during the PK sample collection period.
- Primary Outcome Measures
Name Time Method Pharmacokinetics - Vz/F (sitravatinib) Up to 168 hours after dosing Apparent volume of distribution when dosed orally
Pharmacokinetics - Cmax (sitravatinib) Up to Day 168 hours after dosing Maximum observed plasma concentration
Pharmacokinetics - AUC∞ (sitravatinib) Up to 168 hours after dosing Area under the plasma concentration-time curve from time zero extrapolated to infinity
Pharmacokinetics - tmax (sitravatinib) Up to 168 hours after dosing Terminal elimination half-life
Pharmacokinetics - uf (sitravatinib) Up to 168 hours after dosing Unbound fraction
Pharmacokinetics - CL/F (sitravatinib) Up to 168 hours after dosing Apparent total plasma clearance when dosed orally
Pharmacokinetics - AUClast (sitravatinib) Up to 168 hours after dosing Area under the curve from time zero to the last measured time point
- Secondary Outcome Measures
Name Time Method Adverse Events (AEs) Up to 12 weeks from screening Incidence and severity of AEs
Trial Locations
- Locations (1)
Labcorp Drug Development Clinical Research Unit
🇺🇸Dallas, Texas, United States