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

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)

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

Study Overview

• Status: Completed
• Conditions: GIST - Gastrointestinal Stromal Tumor
• Intervention / Treatment: Drug: Ripretinib; Drug: Repaglinide

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Repaglinide 0.5 mg + Ripretinib 150 mg QD; 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; Oral KIT/PDGFRA kinase inhibitor; Other Names: QINLOCK; Drug: Repaglinide; Oral antihyperglycemic agent

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Deciphera Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2021
• Primary Completion (Actual): November 16, 2023
• Study Completion (Actual): July 29, 2024

Study Registration Dates

• First Submitted: August 24, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Hypoglycemic Agents; Physiological Effects of Drugs; Repaglinide
• Other Study ID Numbers: DCC-2618-01-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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