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

• ClinicalTrials.gov Identifier: NCT04530981
• Recruitment Status: Active, not recruiting
• First Posted: August 28, 2020
• Last Update Posted: April 26, 2024
• Sponsor: Deciphera Pharmaceuticals LLC
• Information provided by (Responsible Party): Deciphera Pharmaceuticals LLC

Tracking Information

• First Submitted Date: August 24, 2020
• First Posted Date: August 28, 2020
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: September 22, 2021
• Actual Primary Completion Date: November 16, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2020)

• Maximum Observed Plasma Concentration for Repaglinide [ Time Frame: 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 [ Time Frame: 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-∞) [ Time Frame: 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-∞

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 18, 2023)

Incidence of Adverse Events [ Time Frame: 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).

Original Secondary Outcome Measures (submitted: August 27, 2020)

Incidence of Adverse Events [ Time Frame: Cycle 1 through study completion (~ 12 months). Each cycle is 28 days. ]

Adverse events [TEAEs, SAEs, AESIs], dose reduction, dose interruption, or discontinuation, vital signs (heart rate [beats/min], and changes in laboratory parameters (chemistry, hematology, urinalysis, coagulation).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Drug-Drug Interaction Study to Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Probe Substrate in Patients With Advanced GIST
• Official Title: 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)
• Brief Summary: Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Substrate
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: GIST - Gastrointestinal Stromal Tumor

Intervention

• Drug: Ripretinib
  Oral KIT/PDGFRA kinase inhibitor
  Other Name: QINLOCK
• Drug: Repaglinide
  Oral antihyperglycemic agent

Study Arms

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.

Interventions:

• Drug: Ripretinib
• Drug: Repaglinide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 25, 2024): 13
• Original Estimated Enrollment (submitted: August 27, 2020): 30
• Estimated Study Completion Date: March 2025
• Actual Primary Completion Date: November 16, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04530981
• Other Study ID Numbers: DCC-2618-01-007
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Deciphera Pharmaceuticals LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Deciphera Pharmaceuticals LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Deciphera Pharmaceuticals LLC
• Verification Date: April 2024