Healthy Adults
Conditions
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.
Interventions
DRUGSitravatinib 50 mg
50 mg Sitravatinib on Day 1 (Group 1A)
DRUGSitravatinib 100 mg
100 mg Sitravatinib on Day 1 (Group 2A)
DRUGItraconazole
Itraconazole QD from Day 9 to Day 18, and Sitravatinib 50 mg at Day 12 (Group 1B)
DRUGRifampin
Rifampin QD from Day 9 to Day 22, and Sitravatinib 100 mg at Day 16 (Group 2B)
Sponsors
Mirati Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
This is a Phase 1, single-center, open-label, 2-cohort, 1-sequence crossover study to investigate the effect of coadministration of a P glycoprotein (P-gp) inhibitor, itraconazole, (Cohort 1) and a P-gp inducer, rifampin, (Cohort 2) in healthy subjects.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics - tmax (sitravatinib) | Up to 168 hours after dosing | Terminal elimination half-life |
| Pharmacokinetics - CL/F (sitravatinib) | Up to 168 hours after dosing | Apparent total plasma clearance when dosed orally |
| Pharmacokinetics - Vz/F (sitravatinib) | Up to 168 hours after dosing | Apparent volume of distribution when dosed orally |
| Pharmacokinetics - uf (sitravatinib) | Up to 168 hours after dosing | Unbound fraction |
| 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 - AUClast (sitravatinib) | Up to 168 hours after dosing | Area under the curve from time zero to the last measured time point |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) | Up to 12 weeks from screening | Incidence and severity of AEs |
Countries
United States
Outcome results
None listed