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

NCT05255276 | Completed Phase 1 FDA Drug

• 1 other identifier: 516-013
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (1)

• Adverse Events (AEs)

  Up to 12 weeks from screening

Study Arms (4)

Group 1 Treatment A

ACTIVE COMPARATOR

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

Group 1 Treatment B

ACTIVE COMPARATOR

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

Group 2 Treatment A

ACTIVE COMPARATOR

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

Group 2 Treatment B

ACTIVE COMPARATOR

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

Interventions

Sitravatinib 50 mg DRUG

50 mg Sitravatinib on Day 1 (Group 1A)

Also known as: MGCD516

Group 1 Treatment A

Sitravatinib 100 mg DRUG

100 mg Sitravatinib on Day 1 (Group 2A)

Also known as: MGCD516

Group 2 Treatment A

Itraconazole DRUG

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

Also known as: Protonix

Group 1 Treatment B

Rifampin DRUG

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

Also known as: Pepcid

Group 2 Treatment B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mirati Therapeutics Inc.: lead

Study Sites (1)

Labcorp Drug Development Clinical Research Unit

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

sitravatinib; Itraconazole; Pantoprazole; Rifampin; Famotidine

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Thiazoles

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 10, 2022
• First Posted: February 24, 2022
• Study Start: February 2, 2022
• Primary Completion: May 12, 2022
• Study Completion: February 10, 2023
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

US (1)