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Een geneesmiddel-geneesmiddelinteractiestudie om de effecten van pelabresib op de farmacokinetiek van repaglinide, midazolam en gecombineerd oraal anticonceptivum te evalueren bij patiënten met gevorderde maligniteiten

8 oktober 2026 bijgewerkt door: Novartis Pharmaceuticals

Een fase 1b, open-label, tweedelig onderzoek om het effect van Pelabresib (DAK539/CPI-0610) op de farmacokinetiek van repaglinide, midazolam en gecombineerd drospirenon/ethinylestradiol oraal anticonceptiemiddel te evalueren bij patiënten met gevorderde maligniteiten

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

24

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • Frankrijk
      • Bordeaux, Frankrijk, 33075
        • Werving
        • Novartis Investigative Site
  • Italië
    • TO
      • Candiolo, TO, Italië, 10060
        • Werving
        • Novartis Investigative Site
  • Spanje
      • Barcelona, Spanje, 08023
        • Werving
        • Novartis Investigative Site
      • Madrid, Spanje, 28040
        • Werving
        • Novartis Investigative Site
      • Madrid, Spanje, 28050
        • Werving
        • Novartis Investigative Site
    • Madrid
      • Pozuelo de Alarcón, Madrid, Spanje, 28223
        • Werving
        • Novartis Investigative Site

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Geneesmiddel: pelabresib

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

Andere namen:
  • DAK539 (voorheen CPI-0610)
Geneesmiddel: repaglinide

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

Geneesmiddel: midazolam

2 mg/mL midazolam oral solution administered orally on Pre-Cycle Day 1 and Cycle 1 Day 14
Experimenteel: 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.
Geneesmiddel: pelabresib

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

Andere namen:
  • DAK539 (voorheen CPI-0610)
Geneesmiddel: drospirenone

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

Geneesmiddel: ethinyl estradiol

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

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Maximum Plasma Concentration (Cmax) of repaglinide, midazolam, and drospirenone and ethinyl estradiol
Tijdsspanne: 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
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
Tijdsspanne: 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
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
Tijdsspanne: 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
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
Tijdsspanne: 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
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.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Apparent Clearance (CL/F) of repaglinide, midazolam, and drospirenone and ethinyl estradiol
Tijdsspanne: 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. CL/F 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.
Apparent Volume of Distribution during Terminal Phase (Vz/F) of repaglinide, midazolam, and drospirenone and ethinyl estradiol
Tijdsspanne: 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. Vz/F 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.
Terminal Half-Life (T½) of repaglinide, midazolam, and drospirenone and ethinyl estradiol
Tijdsspanne: 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. T½ 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.
Maximum Plasma Concentration (Cmax) of pelabresib at steady state
Tijdsspanne: 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 pelabresib at steady state 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 from 0 to 24 hours on Day 14 (AUC₀-24h) of pelabresib at steady state
Tijdsspanne: 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. AUC₀-24h of pelabresib at steady state 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.
Number of Participants with adverse events (AEs), serious AEs (SAEs)
Tijdsspanne: Through study completion, an average of 42 months

Incidence of adverse events by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Through study completion, an average of 42 months

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Novartis Pharmaceuticals

Onderzoekers

  • Studie directeur: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

12 juni 2026

Primaire voltooiing (Geschat)

9 maart 2028

Studie voltooiing (Geschat)

7 april 2028

Studieregistratiedata

Eerst ingediend

6 januari 2026

Eerst ingediend dat voldeed aan de QC-criteria

6 januari 2026

Eerst geplaatst (Werkelijk)

14 januari 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

9 oktober 2026

Laatste update ingediend die voldeed aan QC-criteria

8 oktober 2026

Laatst geverifieerd

1 oktober 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • CDAK539A12102
  • 2025-521000-22-00 (Register-ID: EU CT Number)
  • 2025 (Subsidie/contract van de Amerikaanse NIH)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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