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

NCT07340190 | Not Yet Recruiting Phase 1

• 2 other identifiers: CDAK539A121022025-521000-22-00
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Advanced Malignancies

Keywords

Drug-drug interaction (DDI); Cytochrome P450 (CYP); Advanced Malignancies; oral contraceptive; Pharmacokinetics (PK)

Outcome Measures

Primary Outcomes (4)

• Maximum Plasma Concentration (Cmax) of repaglinide, midazolam, and drospirenone and ethinyl estradiol

  Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax of repaglinide, midazolam and combined oral contraceptive drospirenone and ethinyl estradiol per study group will be listed and summarized using descriptive statistics

  Arm A: Pre-Cycle Day 1/Cycle 1 Day 14 (Predose, 0.25-12 hours); Cycle 1 Days 1/15 (24 hours). Arm B: Pre-Cycle Day 1/Cycle 1 Day 10 (Predose, 0.5-10 hours); Days 2/11 (24 h), 3/12 (48 h), 4/13 (72 h), 5/14 (96 h); Cycle 1 Days 1/15 (120 h). 21-day cycle.

• Time to Maximum Concentration (Tmax) of repaglinide, midazolam, and drospirenone and ethinyl estradiol

  Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax of repaglinide, midazolam and combined oral contraceptive drospirenone and ethinyl estradiol per study group will be listed and summarized using descriptive statistics

  Arm A: Pre-Cycle Day 1/Cycle 1 Day 14 (Predose, 0.25-12 hours); Cycle 1 Days 1/15 (24 hours). Arm B: Pre-Cycle Day 1/Cycle 1 Day 10 (Predose, 0.5-10 hours); Days 2/11 (24 h), 3/12 (48 h), 4/13 (72 h), 5/14 (96 h); Cycle 1 Days 1/15 (120 h). 21-day cycle.

• Area Under the Curve to Last Measurable Concentration (AUClast) of repaglinide, midazolam, and drospirenone and ethinyl estradiol

  Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast of repaglinide, midazolam and combined oral contraceptive drospirenone and ethinyl estradiol per study group will be listed and summarized using descriptive statistics

  Arm A: Pre-Cycle Day 1/Cycle 1 Day 14 (Predose, 0.25-12 hours); Cycle 1 Days 1/15 (24 hours). Arm B: Pre-Cycle Day 1/Cycle 1 Day 10 (Predose, 0.5-10 hours); Days 2/11 (24 h), 3/12 (48 h), 4/13 (72 h), 5/14 (96 h); Cycle 1 Days 1/15 (120 h). 21-day cycle.

• Area Under the Curve to Infinity (AUCinf) of repaglinide, midazolam, and drospirenone and ethinyl estradiol

  Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUCinf of repaglinide, midazolam and combined oral contraceptive drospirenone and ethinyl estradiol per study group will be listed and summarized using descriptive statistics

  Arm A: Pre-Cycle Day 1/Cycle 1 Day 14 (Predose, 0.25-12 hours); Cycle 1 Days 1/15 (24 hours). Arm B: Pre-Cycle Day 1/Cycle 1 Day 10 (Predose, 0.5-10 hours); Days 2/11 (24 h), 3/12 (48 h), 4/13 (72 h), 5/14 (96 h); Cycle 1 Days 1/15 (120 h). 21-day cycle.

Secondary Outcomes (6)

• Apparent Clearance (CL/F) of repaglinide, midazolam, and drospirenone and ethinyl estradiol

  Arm A: Pre-Cycle Day 1/Cycle 1 Day 14 (Predose, 0.25-12 hours); Cycle 1 Days 1/15 (24 hours). Arm B: Pre-Cycle Day 1/Cycle 1 Day 10 (Predose, 0.5-10 hours); Days 2/11 (24 h), 3/12 (48 h), 4/13 (72 h), 5/14 (96 h); Cycle 1 Days 1/15 (120 h). 21-day cycle.

• Apparent Volume of Distribution during Terminal Phase (Vz/F) of repaglinide, midazolam, and drospirenone and ethinyl estradiol

  Arm A: Pre-Cycle Day 1/Cycle 1 Day 14 (Predose, 0.25-12 hours); Cycle 1 Days 1/15 (24 hours). Arm B: Pre-Cycle Day 1/Cycle 1 Day 10 (Predose, 0.5-10 hours); Days 2/11 (24 h), 3/12 (48 h), 4/13 (72 h), 5/14 (96 h); Cycle 1 Days 1/15 (120 h). 21-day cycle.

• Terminal Half-Life (T½) of repaglinide, midazolam, and drospirenone and ethinyl estradiol

  Arm A: Pre-Cycle Day 1/Cycle 1 Day 14 (Predose, 0.25-12 hours); Cycle 1 Days 1/15 (24 hours). Arm B: Pre-Cycle Day 1/Cycle 1 Day 10 (Predose, 0.5-10 hours); Days 2/11 (24 h), 3/12 (48 h), 4/13 (72 h), 5/14 (96 h); Cycle 1 Days 1/15 (120 h). 21-day cycle.

• Maximum Plasma Concentration (Cmax) of pelabresib at steady state

  Arm A: Pre-Cycle Day 1/Cycle 1 Day 14 (Predose, 0.25-12 hours); Cycle 1 Days 1/15 (24 hours). Arm B: Pre-Cycle Day 1/Cycle 1 Day 10 (Predose, 0.5-10 hours); Days 2/11 (24 h), 3/12 (48 h), 4/13 (72 h), 5/14 (96 h); Cycle 1 Days 1/15 (120 h). 21-day cycle.

• Area Under the Curve from 0 to 24 hours on Day 14 (AUC₀-24h) of pelabresib at steady state

  Arm A: Pre-Cycle Day 1/Cycle 1 Day 14 (Predose, 0.25-12 hours); Cycle 1 Days 1/15 (24 hours). Arm B: Pre-Cycle Day 1/Cycle 1 Day 10 (Predose, 0.5-10 hours); Days 2/11 (24 h), 3/12 (48 h), 4/13 (72 h), 5/14 (96 h); Cycle 1 Days 1/15 (120 h). 21-day cycle.

Study Arms (2)

Arm A

EXPERIMENTAL

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.

Drug: pelabresib; Drug: repaglinide; Drug: midazolam

Arm B

EXPERIMENTAL

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.

Drug: pelabresib; Drug: drospirenone; Drug: ethinyl estradiol

Interventions

pelabresib DRUG

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

Also known as: DAK539 (formerly CPI-0610)

Arm A; Arm B

repaglinide DRUG

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

Arm A

midazolam DRUG

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

Arm A

drospirenone DRUG

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

Arm B

ethinyl estradiol DRUG

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

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Platelet count ≥ 150 × 109 /L in the absence of thrombopoietic factors or transfusions within 2 weeks of the screening assessment
• Absolute neutrophil count (ANC) ≥ 1 × 109 /L in the absence of granulocyte growth factors
• 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.
• Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN (≤5 × ULN if the elevation can be ascribed to liver involvement)
• 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).
• Is a female participant.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Interventions

repaglinide; Midazolam; drospirenone; Ethinyl Estradiol

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 14, 2026
• Study Start: May 29, 2026
• Primary Completion (Estimated): March 9, 2028
• Study Completion (Estimated): April 7, 2028
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share