Clinical Trials in Italy / NCT07340190
Recruiting
Phase 1
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 · tracked via the Priya Life Science Italy tracker
Condition(s) studied
Advanced Malignancies
Investigational drug(s) / intervention(s)
pelabresib: pelabresib 225 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break
repaglinide: 0.5 mg repaglinide tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 14
midazolam: 2 mg/mL midazolam oral solution administered orally on Pre-Cycle Day 1 and Cycle 1 Day 14
drospirenone: 3 mg drospirenone tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 10
ethinyl estradiol: 0.03 mg ethinyl estradiol tablet administered orally on Pre-Cycle Day 1 and Cycle 1 Day 10
Study 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.
Eligibility
Key Inclusion Criteria:
Key inclusion criteria for all participants (Arm A and Arm B)
* 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.
Key Exclusion Criteria:
Key exclusion criteria for Arm A
* 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.
Key exclusion criteria for Arm B
* 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.
Other protocol-defined inclusion/exclusion criteria may apply.
Primary outcome measure(s)
- Maximum Plasma Concentration (Cmax) 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.
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 - Time to Maximum Concentration (Tmax) 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.
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 - Area Under the Curve to Last Measurable Concentration (AUClast) 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.
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 - Area Under the Curve to Infinity (AUCinf) 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.
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
Trial sites (6)
| Facility | City | Region | Status |
|---|---|---|---|
| Novartis Investigative Site | Bordeaux | France | Recruiting |
| Novartis Investigative Site | Candiolo | TO | Recruiting |
| Novartis Investigative Site | Pozuelo de Alarcón | Madrid | Recruiting |
| Novartis Investigative Site | Barcelona | Spain | Recruiting |
| Novartis Investigative Site | Madrid | Spain | Recruiting |
| Novartis Investigative Site | Madrid | Spain | Recruiting |
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Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT07340190 on ClinicalTrials.gov ↗ ← All trials in Italy