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

NCT03586726 | Completed Phase 1 Results

• 2 other identifiers: WP406082018-001783-40
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (8)

• Percentage of Participants With Adverse Events

  Up to 21 days postdose

• Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan

  Day 10 of Period 1 and Day 16 of Period 2

• Time to Maximum Observed Plasma Concentration for M2 Metabolite

  Day 10 of Period 1 and Day 16 of Period 2

• Time to Maximum Observed Plasma Concentration for M3 Metabolite

  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

Study Arms (1)

Balovaptan + Rifampicin

EXPERIMENTAL

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; Drug: Rifampicin

Interventions

Balovaptan DRUG

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.

Balovaptan + Rifampicin

Rifampicin DRUG

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.

Balovaptan + Rifampicin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Pra International Group B.V

Groningen, 9728 NZ, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 32935287 DERIVED

MeSH Terms

Interventions

balovaptan; Rifampin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2018
• First Posted: July 16, 2018
• Study Start: July 24, 2018
• Primary Completion: November 2, 2018
• Study Completion: November 15, 2018
• Last Updated: November 7, 2019
• Results First Posted: November 7, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)