Clinical trial NCT03579719: A Study to Investigate the Effect of Itraconazole on the PK of Multiple Doses of Balovaptan in Healthy Volunteers
Official title: A Single-Center, Non-Randomized, Open-Label, One-Sequence, Two-Period Within-Subject Study to Investigate the Effect of Itraconazole on the Pharmacokinetics of Multiple Doses of Balovaptan in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-07-09
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This study was a non-randomized, open-label, one-sequence, two-period within-subject study to investigate the effect of CYP3A inhibition on the PK of balovaptan in healthy male and female volunteers using itraconazole as a CYP3A inhibitor. The study was conducted at 1 site in the Netherlands.


Eligibility criteria: Inclusion Criteria:

* Healthy male and female subjects. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, urinalysis, and serology.
* Body Mass Index of 18 to 30 kg/m2, inclusive.
* For women of childbearing potential: agreement to use at least 2 acceptable contraceptive methods during the treatment period and for 90 days after the last dose of study drug.
* For men: agreement to use contraceptive measures, and agreement to refrain from donating sperm until 90 days after the last dose of study drug.

Exclusion Criteria:

* Female subjects who are pregnant or lactating.
* Any condition or disease detected during the medical interview/physical examination that would render the subject unsuitable for the study, place the subject at undue risk or interfere with the ability of the subject to complete the study in the opinion of the Investigator.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) for Balovaptan
timeFrame: Day 10 of Period 1, Day 10 and Day 15 of Period 2
measure: Maximum Plasma Concentration (Cmax) for M2 Metabolite (as Applicable)
timeFrame: Day 10 of Period 1, Day 10 and Day 15 of Period 2
measure: Maximum Plasma Concentration (Cmax) for M3 Metabolite
timeFrame: Day 10 of Period 1, Day 10 and Day 15 of Period 2
measure: Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for Balovaptan
timeFrame: Day 10 of Period 1, Day 10 and Day 15 of Period 2
measure: Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for M2 Metabolite (as Applicable)
timeFrame: Day 10 of Period 1, Day 10 and Day 15 of Period 2
measure: Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for M3 Metabolite
timeFrame: Day 10 of Period 1, Day 10 and Day 15 of Period 2
measure: Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan
timeFrame: Day 10 of Period 1; Day 10 and Day 15 of Period 2
measure: Time to Maximum Observed Plasma Concentration (Tmax) for M2 Metabolite (as Applicable)
timeFrame: Day 10 of Period 1; Day 10 and Day 15 of Period 2
measure: Time to Maximum Observed Plasma Concentration (Tmax) for M3 Metabolite
timeFrame: Day 10 of Period 1; Day 10 and Day 15 of Period 2
Secondary outcomes:
measure: Trough Plasma Concentration (Ctrough) for Balovaptan
timeFrame: Day 10 of Period 1; Day 10 and Day 15 of Period 2
measure: Trough Plasma Concentration (Ctrough) for M2 Metabolite (as Applicable)
timeFrame: Day 10 of Period 1; Day 10 and Day 15 of Period 2
measure: Trough Plasma Concentration (Ctrough) for M3 Metabolite
timeFrame: Day 10 of Period 1; Day 10 and Day 15 of Period 2
measure: Time to Steady State for Balovaptan
timeFrame: Days 1, 3, 5, 8, 9, 10 in Period 1 and Days 1, 3, 5, 8, 9, 10, 13, 14, 15 in Period 2
measure: Percentage of Participants With Adverse Events
timeFrame: Up to 21 days postdose
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: Pra International Group B.V
Study officials:
References:
citation: Derks MGM, Wandel C, Young A, Bolt SK, Meyenberg C. Open-Label Assessment of the Effects of Itraconazole and Rifampicin on Balovaptan Pharmacokinetics in Healthy Volunteers. Adv Ther. 2020 Nov;37(11):4720-4729. doi: 10.1007/s12325-020-01491-y. Epub 2020 Sep 15.