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

Phase 1

Completed

• Conditions: GIST - Gastrointestinal Stromal Tumor
• Interventions: Drug: Ripretinib; Drug: Repaglinide

• Registration Number: NCT04530981
• Lead Sponsor: Deciphera Pharmaceuticals, LLC

Brief Summary

Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Substrate

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-08-24
• Study First Submitted QC: 2020-08-27
• Study First Posted: 2020-08-28
• Study Start: 2021-09-22
• Primary Completion: 2023-11-16
• Status Verified: 2024-07
• Study Completion: 2024-07-29
• Last Update Submitted: 2024-07-31
• Last Update Posted: 2024-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Patients ≥18 years of age.
2. Patients must have a histologic diagnosis of GIST.
3. Patients must have GIST that has progressed on or have intolerance to at least 2 lines of prior TKI therapies.
4. Patients must have an Eastern Cooperative Oncology Group performance score of ≤ 2.
5. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
6. Adequate organ and bone marrow function.

Exclusion Criteria

1. Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose.

2. Prior treatment with ripretinib.

3. Patients who have had prior repaglinide treatment within 14 days prior to Cycle 1 Day 1.

4. History or presence of clinically relevant cardiovascular abnormalities.

5. Gastrointestinal abnormalities including but not limited to:

   • inability to take oral medication,
   • malabsorption syndromes,
   • requirement for intravenous alimentation.

6. Patients who have type 1 or type 2 diabetes.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Repaglinide 0.5 mg + Ripretinib 150 mg QD	Repaglinide	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.
Repaglinide 0.5 mg + Ripretinib 150 mg QD	Ripretinib	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.

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration for Repaglinide	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.	Measure the Cmax
Area under the concentration-time curve (AUC) from time 0 up to time t (AUC0-t) for Repaglinide	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.	Measure the AUC0-t
AUC from time 0 and extrapolated to infinity (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.	Measure the AUC0-∞

Secondary Outcome Measures

Name	Time	Method
Incidence of Adverse Events	Cycle 1 through study completion (~ 12 months). Each cycle is 28 days.	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).

Trial Locations

Locations (3)

Mayo Clinic Florida; 🇺🇸 Jacksonville, Florida, United States

Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States