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

NCT ID: NCT05255276

Last Updated: 2024-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-02
• Study Completion Date: 2023-02-10

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.

Conditions

Healthy Adults

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Group 1 Treatment A

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 Type: ACTIVE_COMPARATOR

Sitravatinib 50 mg

Intervention Type: DRUG

50 mg Sitravatinib on Day 1 (Group 1A)

Group 1 Treatment B

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 Type: ACTIVE_COMPARATOR

Itraconazole

Intervention Type: DRUG

Itraconazole QD from Day 9 to Day 18, and Sitravatinib 50 mg at Day 12 (Group 1B)

Group 2 Treatment A

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 Type: ACTIVE_COMPARATOR

Sitravatinib 100 mg

Intervention Type: DRUG

100 mg Sitravatinib on Day 1 (Group 2A)

Group 2 Treatment B

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.

Group Type: ACTIVE_COMPARATOR

Rifampin

Intervention Type: DRUG

Rifampin QD from Day 9 to Day 22, and Sitravatinib 100 mg at Day 16 (Group 2B)

Interventions

Sitravatinib 50 mg

50 mg Sitravatinib on Day 1 (Group 1A)

Intervention Type: DRUG

Sitravatinib 100 mg

100 mg Sitravatinib on Day 1 (Group 2A)

Intervention Type: DRUG

Itraconazole

Itraconazole QD from Day 9 to Day 18, and Sitravatinib 50 mg at Day 12 (Group 1B)

Intervention Type: DRUG

Rifampin

Rifampin QD from Day 9 to Day 22, and Sitravatinib 100 mg at Day 16 (Group 2B)

Intervention Type: DRUG

Other Intervention Names

MGCD516; MGCD516; Protonix; Pepcid

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mirati Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Labcorp Drug Development Clinical Research Unit

Dallas, Texas, United States

Countries

United States

Other Identifiers

516-013

Identifier Type: -

Identifier Source: org_study_id