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

NCT ID: NCT07340190

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-05-29
• Study Completion Date: 2029-12-14

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Part 1 (PK profiles of victim drugs):

• Arm A: repaglinide + midazolam + pelabresib

Part 2 (Continued treatment):

After completing Part 1, in case of clinical benefit, participants can continue with pelabresib treatment in Part 2 until the end of study (EOS) is reached or until the participant meets discontinuation criteria, or until they receive pelabresib treatment via alternative means of access, whichever occurs first.

Group Type: EXPERIMENTAL

pelabresib

Intervention Type: DRUG

pelabresib 225 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break

repaglinide

Intervention Type: DRUG

0.5 mg repaglinide tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 14

midazolam

Intervention Type: DRUG

2 mg/mL midazolam oral solution administered orally on Pre-Cycle Day 1 and Cycle 1 Day 14

Arm B

Part 1 (PK profiles of victim drugs):

• Arm B: drospirenone + ethinyl estradiol + pelabresib

Part 2 (Continued treatment):

After completing Part 1, in case of clinical benefit, participants can continue with pelabresib treatment in Part 2 until the end of study (EOS) is reached or until the participant meets discontinuation criteria, or until they receive pelabresib treatment via alternative means of access, whichever occurs first.

Group Type: EXPERIMENTAL

pelabresib

Intervention Type: DRUG

pelabresib 225 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break

drospirenone

Intervention Type: DRUG

3 mg drospirenone tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 10

ethinyl estradiol

Intervention Type: DRUG

0.03 mg ethinyl estradiol tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 10

Interventions

pelabresib

pelabresib 225 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break

Intervention Type: DRUG

repaglinide

0.5 mg repaglinide tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 14

Intervention Type: DRUG

midazolam

2 mg/mL midazolam oral solution administered orally on Pre-Cycle Day 1 and Cycle 1 Day 14

Intervention Type: DRUG

drospirenone

3 mg drospirenone tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 10

Intervention Type: DRUG

ethinyl estradiol

0.03 mg ethinyl estradiol tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 10

Intervention Type: DRUG

Other Intervention Names

DAK539 (formerly CPI-0610)

Eligibility Criteria

Inclusion Criteria

• Is at least 18 years of age at the time of signing the informed consent.
• Has a confirmed documented diagnosis of an advanced malignancy for which no standard and/or curative treatment options are available
• Has the following acceptable laboratory assessments prior to the first dose of study treatment:

1. Platelet count ≥ 150 × 109 /L in the absence of thrombopoietic factors or transfusions within 2 weeks of the screening assessment

2. Absolute neutrophil count (ANC) ≥ 1 × 109 /L in the absence of granulocyte growth factors

3. Peripheral blood blast count < 5%. Assessment of blasts in bone marrow is not mandatory at screening; however, blasts must be <5% if the bone marrow assessment is performed.

4. Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN)

5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN (≤5 × ULN if the elevation can be ascribed to liver involvement)

6. Calculated or measured creatinine clearance of ≥30 mL/min*

• Has fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy (residual Grade 1 toxicities and residual alopecia of any grade are allowed).

Additional inclusion criterion for Arm B

• Is a female participant.

Exclusion Criteria

• Has a history of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical class.
• Is pregnant (confirmed by a pregnancy test at screening) or is breastfeeding.
• Has current known active or chronic infection with HIV, hepatitis B, or hepatitis C.
• Has impaired cardiac function or clinically significant cardiac disease.
• Has a gastrointestinal tumor, impaired GI function, GI disease, or significant resection of stomach or other portion of the gastrointestinal tract that could alter the absorption of pelabresib, midazolam, or repaglinide, including any unresolved nausea, vomiting, or diarrhea.

• Has renal impairment (CrCl less than 50 mL/min).
• Has a gastrointestinal tumor, impaired GI function, GI disease, or significant resection of stomach or other portion of the gastrointestinal tract that could alter the absorption of pelabresib, drospirenone and ethinyl estradiol, including any unresolved nausea, vomiting, or diarrhea.
• Has breast cancer or other estrogen- or progestin-sensitive cancer.
• Has undiagnosed abnormal uterine bleeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Central Contacts

Novartis Pharmaceuticals

Role: CONTACT

novartis.email@novartis.com

+41613241111

Novartis Pharmaceuticals

Role: CONTACT

novartis.email@novartis.com

Other Identifiers

2025-521000-22-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDAK539A12102

Identifier Type: -

Identifier Source: org_study_id