NCT07340190

A Drug-drug Interaction Study to Evaluate the Effects of Pelabresib on the Pharmacokinetics of Repaglinide, Midazolam, and Combined Oral Contraceptive in Patients With Advanced Malignancies

A Phase 1b, Open Label, 2-Part Study to Evaluate the Effect of Pelabresib (DAK539/CPI-0610) on the Pharmacokinetics of Repaglinide, Midazolam, and Combined Drospirenone/Ethinyl Estradiol Oral Contraceptive in Patients With Advanced Malignancies

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This drug-drug interaction (DDI) study aims to evaluate the impact of pelabresib at steady-state plasma concentrations on the pharmacokinetic (PK) profile of A) a single dose of repaglinide and a single dose of midazolam, and B) a single dose of combined drospirenone and ethinyl estradiol. The study will be conducted in adult participants with advanced malignancies for whom no standard or curative treatment options are available.

Detailed description

This clinical study is divided into two components: 1. Part 1: Interventional Phase This phase evaluates the drug-drug interaction (DDI) potential of pelabresib with specific victim drugs. * Arm A: Assesses pelabresib's DDI potential with repaglinide and midazolam. Participants will be hospitalized for two nights-one starting on Pre-cycle Day 1 and another on Day 14. Beginning Cycle 1 Day 1, participants will receive 225 mg of pelabresib daily for 14 days, followed by a 7-day break. * Arm B: Evaluates pelabresib's DDI potential with drospirenone and ethinyl estradiol. Hospitalization will range from a minimum of 2 nights to a maximum of 10 nights-up to 5 nights starting on Pre-cycle Day 1, and up to 5 nights starting on Cycle 1 Day 10. Participants will follow the same pelabresib dosing schedule as Arm A. Arm B will proceed independently of Arm A's results. 2. Part 2: Continued Treatment Phase Participants demonstrating clinical benefit, as determined by the investigator, may continue receiving pelabresib in additional treatment cycles. A participant is considered to have entered the screening period upon signing the informed consent form. Enrollment occurs when the participant is assigned their first dose of study treatment via the IRT system. Completion is defined as having finished all study phases, including the End of Treatment (EOT) and the 30-day Safety Follow-Up visits. Participants with hematological malignancies will continue follow-up every 3 months after EOT. 1. End of Treatment Visit Must occur within 7 days of the last pelabresib dose or within 7 days of the decision to discontinue treatment, if that decision is made more than 7 days after the last dose. 2. 30-Day Safety Follow-Up All participants will be monitored for adverse events (AEs) and serious adverse events (SAEs) for 30 ± 3 days after the final pelabresib dose. If a participant initiates another anticancer therapy or transitions to pelabresib via another source (e.g., extension study or commercial supply), safety follow-up ends at the start of the new treatment. 3. Leukemic Transformation Monitoring Participants with hematological malignancies will be followed every 3 months after EOT for signs of leukemic transformation, continuing until one of the following: study end, confirmation of acute myeloid leukemia (AML), withdrawal of consent, loss to follow-up, or death.

Conditions

• Advanced Malignancies

Interventions

Type	Name	Description
DRUG	pelabresib	pelabresib 225 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break
DRUG	repaglinide	0.5 mg repaglinide tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 14
DRUG	midazolam	2 mg/mL midazolam oral solution administered orally on Pre-Cycle Day 1 and Cycle 1 Day 14
DRUG	drospirenone	3 mg drospirenone tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 10
DRUG	ethinyl estradiol	0.03 mg ethinyl estradiol tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 10

Timeline

• Start date: 2026-05-29
• Primary completion: 2028-03-09
• Completion: 2028-04-07
• First posted: 2026-01-14
• Last updated: 2026-04-02