A Drug-Drug Interaction Study to Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Probe Substrate in Patients With Advanced GIST

Study Overview
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Brief Summary
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Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Substrate

Official Title
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A Phase 1 Open-label, Multicenter Study to Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Probe Substrate (Repaglinide) in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)

Conditions
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GIST - Gastrointestinal Stromal Tumor

Intervention / Treatment
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* Drug: Ripretinib
* Drug: Repaglinide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years of age. Patients must have a histologic diagnosis of GIST. Patients must have GIST that has progressed on or have intolerance to at least 2 lines of prior TKI therapies. Patients must have an Eastern Cooperative Oncology Group performance score of ≤ 2. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements. Adequate organ and bone marrow function. Exclusion Criteria: Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose. Prior treatment with ripretinib. Patients who have had prior repaglinide treatment within 14 days prior to Cycle 1 Day 1. History or presence of clinically relevant cardiovascular abnormalities. Gastrointestinal abnormalities including but not limited to: inability to take oral medication, malabsorption syndromes, requirement for intravenous alimentation. Patients who have type 1 or type 2 diabetes.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Repaglinide 0.5 mg + Ripretinib 150 mg QD<br>A single dose of repaglinide 0.5 mg (1 × 0.5-mg tablet) will be administered orally on Cycle 1 Day 1 and Cycle 1 Day 15. Ripretinib 150 mg QD (3 × 50-mg tablets) will be administered orally from Day 2 through Day 28 for Cycle 1 and will be administered continuously from Cycle 2 until disease progression as assessed by the Investigator, unacceptable toxicity, or withdrawal of consent. | Drug: Ripretinib<br>* Oral KIT/PDGFRA kinase inhibitor<br>* Other names: QINLOCK;Drug: Repaglinide<br>* Oral antihyperglycemic agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration for Repaglinide | Measure the Cmax | Cycle 1 Day 1 and Cycle 1 Day 15 (pre-dose and at multiple time points [up to 24 hours] post-dose). Each cycle is 28 days. | 
| Area under the concentration-time curve (AUC) from time 0 up to time t (AUC0-t) for Repaglinide | Measure the AUC0-t | Cycle 1 Day 1 and Cycle 1 Day 15 (pre-dose and at multiple time points [up to 24 hours] post-dose). Each cycle is 28 days. | 
| AUC from time 0 and extrapolated to infinity (AUC0-∞) | Measure the AUC0-∞ | Cycle 1 Day 1 and Cycle 1 Day 15 (pre-dose and at multiple time points [up to 24 hours] post-dose). Each cycle is 28 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | Adverse events [TEAEs, SAEs], dose reduction, dose interruption, or discontinuation, vital signs (heart rate [beats/min], and changes in laboratory parameters (chemistry, hematology, urinalysis, coagulation). | Cycle 1 through study completion (  12 months). Each cycle is 28 days. |