A Study to Investigate the Effect of Itraconazole on the PK of Multiple Doses of Balovaptan in Healthy Volunteers

NCT03579719 | Completed Phase 1 Results

• 2 other identifiers: WP406092018-001454-10
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (9)

• 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, Day 10 and Day 15 of Period 2

• Maximum Plasma Concentration (Cmax) for M2 Metabolite (as Applicable)

  Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.

  Day 10 of Period 1, Day 10 and Day 15 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, Day 10 and Day 15 of Period 2

• Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for Balovaptan

  Day 10 of Period 1, Day 10 and Day 15 of Period 2

• Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for M2 Metabolite (as Applicable)

  Day 10 of Period 1, Day 10 and Day 15 of Period 2

• Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for M3 Metabolite

  Day 10 of Period 1, Day 10 and Day 15 of Period 2

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

  Day 10 of Period 1; Day 10 and Day 15 of Period 2

• Time to Maximum Observed Plasma Concentration (Tmax) for M2 Metabolite (as Applicable)

  Day 10 of Period 1; Day 10 and Day 15 of Period 2

• Time to Maximum Observed Plasma Concentration (Tmax) for M3 Metabolite

  Day 10 of Period 1; Day 10 and Day 15 of Period 2

Secondary Outcomes (5)

• Trough Plasma Concentration (Ctrough) for Balovaptan

  Day 10 of Period 1; Day 10 and Day 15 of Period 2

• Trough Plasma Concentration (Ctrough) for M2 Metabolite (as Applicable)

  Day 10 of Period 1; Day 10 and Day 15 of Period 2

• Trough Plasma Concentration (Ctrough) for M3 Metabolite

  Day 10 of Period 1; Day 10 and Day 15 of Period 2

• Time to Steady State for Balovaptan

  Days 1, 3, 5, 8, 9, 10 in Period 1 and Days 1, 3, 5, 8, 9, 10, 13, 14, 15 in Period 2

• Percentage of Participants With Adverse Events

  Up to 21 days postdose

Study Arms (1)

Balovaptan + Itraconzole

EXPERIMENTAL

Dosing in Period 1 was separated by at least a 7 day washout period before dosing starts in Period 2. Participants received the study drugs in 2 periods over a total of 37 days.

Drug: Balovaptan; Drug: Itraconazole

Interventions

Balovaptan DRUG

In Period 1, balovaptan was administered orally once daily (qd) on Days 1 to 10. In Period 2, balovaptan was administered qd on Days 6 to 20.

Balovaptan + Itraconzole

Itraconazole DRUG

In Period 2, 200 mg itraconzole was administered bid for 4 days and qd on Days 5-20, approximately 12 hours apart. On Days 6-20, 200 mg itraconazole was administered qd.

Balovaptan + Itraconzole

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.

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; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

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: June 26, 2018
• First Posted: July 9, 2018
• Study Start: July 10, 2018
• Primary Completion: November 9, 2018
• Study Completion: November 9, 2018
• Last Updated: November 4, 2019
• Results First Posted: November 4, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)