A Study to Investigate the Effect of Rifampicin on the PK of Multiple Doses of Balovaptin In Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Balovaptan; Drug: Rifampicin

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • Pra International Group B.V

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Balovaptan + Rifampicin; Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2.	Drug: Balovaptan; In Period 1, balovaptan was administered alone as a once daily (qd) dose on Days 1 to 10. In Period 2, balovaptan was administered as a qd dose on Days 7 to 16.; Drug: Rifampicin; In Period 2, 600 mg of rifampicin will be administered alone as a qd dose from Day 1 to Day 6, and as a qd dose on Days 7 to 16.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) for Balovaptan	Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.	Day 10 of Period 1 and Day 16 of Period 2
Maximum Plasma Concentration (Cmax) for M2 Metabolite	Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.	Day 10 of Period 1 and Day 16 of Period 2
Maximum Plasma Concentration (Cmax) for M3 Metabolite	Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.	Day 10 of Period 1 and Day 16 of Period 2
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours (AUC0-24) for Balovaptan	AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose.	Day 10 and 11 of Period 1; Day 16 and 17 of Period 2
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M2 Metabolite	AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose.	Day 10 and 11 of Period 1; Day 16 and 17 of Period 2
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M3 Metabolite	AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose.	Day 10 and 11 of Period 1; Day 16 and 17 of Period 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events		Up to 21 days postdose
Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan	Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units.	Day 10 of Period 1 and Day 16 of Period 2
Time to Maximum Observed Plasma Concentration for M2 Metabolite	Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units.	Day 10 of Period 1 and Day 16 of Period 2
Time to Maximum Observed Plasma Concentration for M3 Metabolite	Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units.	Day 10 of Period 1 and Day 16 of Period 2
Metabolite to Parent Ratio for M2 Metabolite Based on AUC0-24		Day 10 and 11 of Period 1; Day 16 and 17 of Period 2
Metabolite to Parent Ratio for M2 Metabolite Based on Cmax		Day 10 of Period 1 and Day 16 of Period 2
Metabolite to Parent Ratio for M3 Metabolite Based on AUC0-24		Day 10 and 11 of Period 1; Day 16 and 17 of Period 2
Metabolite to Parent Ratio for M3 Metabolite Based on Cmax		Day 10 of Period 1 and Day 16 of Period 2

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2018
• Primary Completion (Actual): November 2, 2018
• Study Completion (Actual): November 15, 2018

Study Registration Dates

• First Submitted: July 3, 2018
• First Submitted That Met QC Criteria: July 3, 2018
• First Posted (Actual): July 16, 2018

Study Record Updates

• Last Update Posted (Actual): November 7, 2019
• Last Update Submitted That Met QC Criteria: October 15, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin
• Other Study ID Numbers: WP40608; 2018-001783-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No