Clinical trial NCT05255276: PK Study to Assess Drug-drug Interaction Between Sitravatinib and a P-gp Inducer and an Inhibitor.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adults
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-24
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: OTHER

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.


Eligibility 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.

Primary outcomes:
measure: Pharmacokinetics - Cmax (sitravatinib)
timeFrame: Up to Day 168 hours after dosing
measure: Pharmacokinetics - AUC∞ (sitravatinib)
timeFrame: Up to 168 hours after dosing
measure: Pharmacokinetics - AUClast (sitravatinib)
timeFrame: Up to 168 hours after dosing
measure: Pharmacokinetics - tmax (sitravatinib)
timeFrame: Up to 168 hours after dosing
measure: Pharmacokinetics - CL/F (sitravatinib)
timeFrame: Up to 168 hours after dosing
measure: Pharmacokinetics - Vz/F (sitravatinib)
timeFrame: Up to 168 hours after dosing
measure: Pharmacokinetics - uf (sitravatinib)
timeFrame: Up to 168 hours after dosing
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: Up to 12 weeks from screening
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Labcorp Drug Development Clinical Research Unit
state: Texas
Study officials:
References: