Clinical trial NCT03586726: A Study to Investigate the Effect of Rifampicin on the PK of Multiple Doses of Balovaptin In Healthy Volunteers
Official title: A Single-Center, Non-Randomized, Open-Label, One-Sequence, Two-Period Within-Subject Study to Investigate the Effect of Rifampicin on the Pharmacokinetics of Multiple Doses of Balovaptin In Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-07-16
Enrollment: 16
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 single-center, non-randomized, open-label, one-sequence, two-period, within-subject study to investigate the effects of multiple doses of rifampicin on the PK and safety of multiple doses of balovaptan in healthy subjects. 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.

Rifampicin-related Exclusion Criteria:

* Subjects diagnosed, or suspected of having porphyria, and subjects with first-degree relatives diagnosed, or suspected of having porphyria.
* Known hypersensitivity to rifampicin

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) for Balovaptan
timeFrame: Day 10 of Period 1 and Day 16 of Period 2
measure: Maximum Plasma Concentration (Cmax) for M2 Metabolite
timeFrame: Day 10 of Period 1 and Day 16 of Period 2
measure: Maximum Plasma Concentration (Cmax) for M3 Metabolite
timeFrame: Day 10 of Period 1 and Day 16 of Period 2
measure: Area Under the Plasma Concentration Curve From Time 0 to 24 Hours (AUC0-24) for Balovaptan
timeFrame: Day 10 and 11 of Period 1; Day 16 and 17 of Period 2
measure: Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M2 Metabolite
timeFrame: Day 10 and 11 of Period 1; Day 16 and 17 of Period 2
measure: Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M3 Metabolite
timeFrame: Day 10 and 11 of Period 1; Day 16 and 17 of Period 2
Secondary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Up to 21 days postdose
measure: Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan
timeFrame: Day 10 of Period 1 and Day 16 of Period 2
measure: Time to Maximum Observed Plasma Concentration for M2 Metabolite
timeFrame: Day 10 of Period 1 and Day 16 of Period 2
measure: Time to Maximum Observed Plasma Concentration for M3 Metabolite
timeFrame: Day 10 of Period 1 and Day 16 of Period 2
measure: Metabolite to Parent Ratio for M2 Metabolite Based on AUC0-24
timeFrame: Day 10 and 11 of Period 1; Day 16 and 17 of Period 2
measure: Metabolite to Parent Ratio for M2 Metabolite Based on Cmax
timeFrame: Day 10 of Period 1 and Day 16 of Period 2
measure: Metabolite to Parent Ratio for M3 Metabolite Based on AUC0-24
timeFrame: Day 10 and 11 of Period 1; Day 16 and 17 of Period 2
measure: Metabolite to Parent Ratio for M3 Metabolite Based on Cmax
timeFrame: Day 10 of Period 1 and Day 16 of Period 2
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.