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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Adults
• Intervention / Treatment: Drug: Sitravatinib 50 mg; Drug: Itraconazole; Drug: Sitravatinib 100 mg; Drug: Rifampin

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Labcorp Drug Development Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Sitravatinib 50 mg; 50 mg Sitravatinib on Day 1 (Group 1A); Other Names: MGCD516
Active Comparator: 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.	Drug: Itraconazole; Itraconazole QD from Day 9 to Day 18, and Sitravatinib 50 mg at Day 12 (Group 1B); Other Names: Protonix
Active Comparator: 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.	Drug: Sitravatinib 100 mg; 100 mg Sitravatinib on Day 1 (Group 2A); Other Names: MGCD516
Active Comparator: 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.	Drug: Rifampin; Rifampin QD from Day 9 to Day 22, and Sitravatinib 100 mg at Day 16 (Group 2B); Other Names: Pepcid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Cmax (sitravatinib)	Maximum observed plasma concentration	Up to Day 168 hours after dosing
Pharmacokinetics - AUC∞ (sitravatinib)	Area under the plasma concentration-time curve from time zero extrapolated to infinity	Up to 168 hours after dosing
Pharmacokinetics - AUClast (sitravatinib)	Area under the curve from time zero to the last measured time point	Up to 168 hours after dosing
Pharmacokinetics - tmax (sitravatinib)	Terminal elimination half-life	Up to 168 hours after dosing
Pharmacokinetics - CL/F (sitravatinib)	Apparent total plasma clearance when dosed orally	Up to 168 hours after dosing
Pharmacokinetics - Vz/F (sitravatinib)	Apparent volume of distribution when dosed orally	Up to 168 hours after dosing
Pharmacokinetics - uf (sitravatinib)	Unbound fraction	Up to 168 hours after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Incidence and severity of AEs	Up to 12 weeks from screening

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2022
• Primary Completion (Actual): May 12, 2022
• Study Completion (Actual): February 10, 2023

Study Registration Dates

• First Submitted: February 10, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): February 24, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Itraconazole
• Other Study ID Numbers: 516-013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No