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A Drug-drug Interaction Study to Assess the Effect of Phenytoin and Itraconazole on the Pharmacokinetics of Pelabresib in Healthy Participants

ConditionHealthy Participants
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-55
SponsorNovartis Pharmaceuticals

About this trial

The purpose of this study is to assess the effect of multiple doses of phenytoin, a strong cytochrome P450 (CYP)3A4 inducer, and itraconazole, a strong CYP3A4 inhibitor, on the pharmacokinetic (PK) profile of DAK539 (hereafter referred to as pelabresib) after a single dose in healthy participants. In addition, the safety and tolerability of a single dose of pelabresib with and without the co-administration of itraconazole or phenytoin will be evaluated.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Participants willing to adhere to the protocol requirements and to provide written informed consent prior to participation in the study.

Healthy male and non-childbearing potential female participants between 18 and 55 years of age, inclusive.

In good health as determined by no clinically significant findings from medical history, physical examination, vital signs, electrocardiograms (ECG) and laboratory tests.

Body Mass Index (BMI) within the range of 18.5 to 29.9 kg/m2, inclusive, with body weight at least 50.0 kg at screening.

Disqualifiers

History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants.

History of clinically significant cardiovascular, renal, hepatic, testicular, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the Investigator.

Clinically significant abnormal clinical chemistry, hematology, coagulation, or urinalysis as judged by the Investigator at screening or first baseline (admission).

Evidence of renal impairment as indicated by creatinine or blood urea level > 1.0 × upper limit of normal (ULN) or clinically significant microalbuminuria or hematuria or clinically significant elevated cystatin-C at screening; evidence of urinary obstruction, or difficulty in voiding at screening; evidence of congenital renal abnormalities with known effect on renal function; calculated estimated glomerular filtration rate (eGFR) < 80 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula for adults at Screening.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Pelabresib

    Drug

    Oral dosing

  • Phenytoin

    Drug

    Oral dosing

  • Itraconazole

    Drug

    Oral dosing

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: Part 1: Pelabresib + PhenytoinExperimental treatment 2 interventions
Group B: Part 2: Pelabresib + ItraconazoleExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Part 1 and 2: Maximum observed plasma concentration (Cmax) of pelabresib

Pharmacokinetic (PK) parameters determined using the actual recorded sampling times and non- compartmental method(s) from the pelabresib plasma concentration-time data.

Time frame
From pre-dose up to 48 or 72 hours after pelabresib administration
2

Part 1 and 2: Area under the plasma concentration-time curve from time 0 to the last measurable concentration sampling time (AUClast) of pelabresib

PK parameters determined using the actual recorded sampling times and non- compartmental method(s) from the pelabresib plasma concentration-time data.

Time frame
From pre-dose up to 48 or 72 hours after pelabresib administration
3

Part 1 and 2: Area under the plasma concentration-time curve from time 0 to infinity (AUCinf) of pelabresib

PK parameters determined using the actual recorded sampling times and non- compartmental method(s) from the pelabresib plasma concentration-time data.

Time frame
From pre-dose up to 48 or 72 hours after pelabresib administration
4

Part 1 and 2: Time to reach maximum plasma concentration (Tmax) of pelabresib

PK parameters determined using the actual recorded sampling times and non- compartmental method(s) from the pelabresib plasma concentration-time data.

Time frame
From pre-dose up to 48 or 72 hours after pelabresib administration

Secondary outcomes

1

Part 1 and 2: Apparent plasma clearance (CL/F) of pelabresib

Pharmacokinetic (PK) parameters determined using the actual recorded sampling times and non- compartmental method(s) from the pelabresib plasma concentration-time data.

Time frame
From pre-dose up to 48 or 72 hours after pelabresib administration
2

Part 1 and 2: Apparent volume of distribution during the terminal elimination phase (Vz/F) of pelabresib

Pharmacokinetic (PK) parameters determined using the actual recorded sampling times and non- compartmental method(s) from the pelabresib plasma concentration-time data.

Time frame
From pre-dose up to 48 or 72 hours after pelabresib administration
3

Part 1 and 2: Terminal elimination half-life (T1/2) of pelabresib

Pharmacokinetic (PK) parameters determined using the actual recorded sampling times and non- compartmental method(s) from the pelabresib plasma concentration-time data.

Time frame
From pre-dose up to 48 or 72 hours after pelabresib administration
4

Part 1 and 2: Incidence of adverse events (AEs) and serious adverse events (SAEs)

Number of participants with AEs and SAEs, including changes in vital signs, electrocardiograms and laboratory values qualifying and reported as AEs.

Time frame
Up to approximately 30 days after the last dose of study drug (Day 48 in Part 1 and Day 40 in Part 2)

Other outcomes

Sponsors and contacts

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Novartis Pharmaceuticals

Lead sponsor

Source ClinicalTrials.gov
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