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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

ConditionAdvanced Malignancies
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNovartis Pharmaceuticals

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

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

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • pelabresib

    Drug

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

  • repaglinide

    Drug

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

  • midazolam

    Drug

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

  • drospirenone

    Drug

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

  • ethinyl estradiol

    Drug

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

Treatment groups

24 Participants
are divided into 2 treatment groups
Group A: Arm AExperimental treatment 3 interventions
Group B: Arm BExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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

Time frame
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.
2

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

Time frame
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.
3

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

Time frame
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.
4

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

Time frame
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

1

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

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.

Time frame
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.
2

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

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.

Time frame
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.
3

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

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

Time frame
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.
4

Maximum Plasma Concentration (Cmax) of pelabresib at steady state

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.

Time frame
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.

Other outcomes

Sponsors and contacts

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Novartis Pharmaceuticals

Lead sponsor

Source ClinicalTrials.gov
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