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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 15
• 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: Yes
• 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.

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 + Itraconzole; 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; 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.; Drug: Itraconazole; 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.

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, 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 Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Adverse Events	Up to 21 days postdose
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

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 10, 2018
• Primary Completion (Actual): November 9, 2018
• Study Completion (Actual): November 9, 2018

Study Registration Dates

• First Submitted: June 26, 2018
• First Submitted That Met QC Criteria: June 26, 2018
• First Posted (Actual): July 9, 2018

Study Record Updates

• Last Update Posted (Actual): November 4, 2019
• Last Update Submitted That Met QC Criteria: October 14, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: WP40609; 2018-001454-10 (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