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A Study to Investigate the Effect of Esomeprazole and the Effect of Food on the Pharmacokinetics of Balovaptan in Healthy Volunteers

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT04156646
Collaborator
(none)
16
Enrollment
1
Location
2
Arms
1.6
Actual Duration (Months)
10.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will investigate the effect of food and the effect of esomeprazole on the pharmacokinetics (PK) of a single dose of balovaptan in healthy volunteers.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Single-Center, Part-Randomized, Open-Label, Single-Dose, Three-Period, Crossover Study to Investigate the Effect of Esomeprazole and The Effect of Food on the Pharmacokinetics of Balovaptan in Healthy Volunteers
Actual Study Start Date :
Nov 19, 2019
Actual Primary Completion Date :
Dec 24, 2019
Actual Study Completion Date :
Jan 6, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment sequence ABC

In Period 1 participants will receive 1 tablet of balovaptan after high-fat, high-calorie meal. In Period 2, after 12 to 21 days wash-out, participants will receive 1 tablet of balovaptan after 10-hour fast. In Period 3 participants will receive esomeprazole administered once daily for 6 days and with a single oral dose of balovaptan in the fasted state 1 hour after the fifth esomeprazole dose

Drug: Balovaptan
Balovaptan will be administered after a high-fat, high-calorie meal (Treatment A), after a 10-hour fast (Treatment B), and after a 10-hour fast with esomeprazole 40 mg (Treatment C)

Drug: Esomeprazole
Esomeprazole will be administered once daily for 6 days and with a single dose of balovaptan 1 hour after the fifth esomeprazole dose
Experimental: Treatment sequence BAC

In Period 1 participants will receive 1 tablet of balovaptan after 10-hour fast. In Period 2, after 12 to 21 days wash-out, participants will receive 1 tablet of balovaptan after high-fat, high-calorie meal. In Period 3 participants will receive esomeprazole administered once daily for 6 days and with a single oral dose of balovaptan in the fasted state 1 hour after the fifth esomeprazole dose

Drug: Balovaptan
Balovaptan will be administered after a high-fat, high-calorie meal (Treatment A), after a 10-hour fast (Treatment B), and after a 10-hour fast with esomeprazole 40 mg (Treatment C)

Drug: Esomeprazole
Esomeprazole will be administered once daily for 6 days and with a single dose of balovaptan 1 hour after the fifth esomeprazole dose

Outcome Measures

Primary Outcome Measures

  1. Maximum Plasma Concentration (Cmax) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Maximum plasma concentration of Balovaptan is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units

  2. Mean Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Area under the plasma concentration-time curve (time 0 to infinity) of Balovaptan is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.

  3. Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose]

    Area under the plasma concentration-time curve of Balovaptan from time 0 to 24 hours post-dose is estimated using non-compartmental methods from the concentration-time profiles.

  4. Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of Balovaptan is estimated using non-compartmental methods from the concentration-time profiles.

  5. Time to Reach Cmax in Plasma (Tmax) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Time to maximum plasma concentration of Balovaptan is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.

  6. Last Quantifiable Concentration (Clast) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.

  7. Time To the Last Quantifiable Concentration (Tlast) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Time to last quantifiable concentration is based on last detectable concentration in the time curve.

  8. Time Between Dosing and Time of First Balovaptan Plasma Concentration (Tlag) [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Time between dosing and time of first balovaptan plasma concentration is estimated using non-compartmental methods from the concentration-time profiles.

  9. Apparent Clearance (Cl/F) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Apparent clearance is estimated using non-compartmental methods from the concentration-time profiles.

  10. Apparent Volume of Distribution (Vd/F) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Apparent volume of distribution is estimated using non-compartmental methods from the concentration-time profiles.

  11. Terminal Elimination Phase Half-Life (T1/2) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.

  12. Terminal Phase Rate Constant (λz) of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Terminal phase rate constant is estimated using non-compartmental methods from the concentration-time profiles.

  13. Plasma Concentrations of Balovaptan [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Amount of Balovaptan in a given volume of plasma.

Secondary Outcome Measures

  1. Maximum Plasma Concentration (Cmax) of M2 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Maximum plasma concentration of M2 Metabolite is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units

  2. Maximum Plasma Concentration (Cmax) of M3 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Maximum plasma concentration of M3 Metabolite is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units

  3. Maximum Plasma Concentration (Cmax) of Esomeprazole [Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose]

    Maximum plasma concentration of Esomeprazole is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units

  4. Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M2 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Area under the plasma concentration-time curve (time 0 to infinity) of M2 Metabolite is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.

  5. Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M3 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Area under the plasma concentration-time curve (time 0 to infinity) of M3 Metabolite is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.

  6. Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Esomeprazole [Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose]

    Area under the plasma concentration-time curve (time 0 to infinity) of Esomeprazole is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.

  7. Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M2 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose]

    Area under the plasma concentration-time curve of M2 Metabolite from time 0 to 24 hours post-dose is estimated using non-compartmental methods from the concentration-time profiles.

  8. Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M3 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose]

    Area under the plasma concentration-time curve of M3 Metabolite from time 0 to 24 hours post-dose is estimated using non-compartmental methods from the concentration-time profiles.

  9. Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M2 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of M2 Metabolite is estimated using non-compartmental methods from the concentration-time profiles.

  10. Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M3 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of M3 Metabolite is estimated using non-compartmental methods from the concentration-time profiles.

  11. Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Esomeprazole [Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose]

    Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of Esomeprazole is estimated using non-compartmental methods from the concentration-time profiles.

  12. Time to Reach Cmax in Plasma (Tmax) of M2 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Time to maximum plasma concentration of M2 Metabolite is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.

  13. Time to Reach Cmax in Plasma (Tmax) of M3 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Time to maximum plasma concentration of M3 Metabolite is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.

  14. Time to Reach Cmax in Plasma (Tmax) of Esomeprazole [Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose]

    Time to maximum plasma concentration of Esomeprazole is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.

  15. Last Quantifiable Concentration (Clast) of M2 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.

  16. Last Quantifiable Concentration (Clast) of M3 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.

  17. Last Quantifiable Concentration (Clast) of Esomeprazole [Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose]

    Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.

  18. Time To the Last Quantifiable Concentration (Tlast) of M2 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Time to last quantifiable concentration is based on last detectable concentration in the time curve.

  19. Time To the Last Quantifiable Concentration (Tlast) of M3 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Time to last quantifiable concentration is based on last detectable concentration in the time curve.

  20. Time To the Last Quantifiable Concentration (Tlast) of Esomeprazole [Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose]

    Time to last quantifiable concentration is based on last detectable concentration in the time curve.

  21. Terminal Elimination Phase Half-Life (T1/2) of M2 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.

  22. Terminal Elimination Phase Half-Life (T1/2) of M3 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.

  23. Terminal Elimination Phase Half-Life (T1/2) of Esomeprazole [Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose]

    Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.

  24. Percentage of Patricipants With Adverse Events (AEs) [Randomization to end of study (up to approximately 7 weeks)]

  25. Terminal Phase Rate Constant (λz) of M2 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Terminal phase rate constant is estimated using non-compartmental methods from the concentration-time profiles.

  26. Terminal Phase Rate Constant (λz) of M3 Metabolite [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Terminal phase rate constant is estimated using non-compartmental methods from the concentration-time profiles.

  27. Terminal Phase Rate Constant (λz) of Esomeprazole [Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose]

    Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.

  28. Plasma Concentrations of M2 Analyte [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Amount of M2 Analyte in a given volume of plasma.

  29. Plasma Concentrations of M3 Analyte [Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose]

    Amount of M3 Analyte in a given volume of plasma.

  30. Plasma Concentrations of Esomeprazole [Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose]

    Amount of Esomeprazole in a given volume of plasma.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

  • No evidence of any active or chronic disease

  • Body mass index (BMI) between 18 and 32 kg/m2 inclusive, at screening

  • For women of childbearing potential: if engaging in heterosexual activity, agreement to use at least two adequate forms of contraception during the entire study and for 90 days following the last dose of study drug

  • For men: agreement to use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

  • Pregnancy or lactation (positive serum pregnancy test at screening or at admission)

  • 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

  • In the opinion of the Investigator, any major illness within 4 weeks prior to the screening examination or any febrile illness within 1 week prior to screening.

  • History of any clinically significant, as determined by the investigator, gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological, lymphatic, musculoskeletal, genitourinary, immunological, dermatological, or connective tissue or allergic disease, metabolic disorder, or cancer

  • Signs and symptoms potentially indicative of peripheral neuropathy

  • History or evidence of any medical condition potentially altering the absorption, distribution, metabolism, or elimination of drugs

  • A history of clinically significant in the opinion of the Investigator hypersensitivity

  • History or presence of clinically significant ECG abnormalities before study drug administration

  • Clinically significant abnormalities in laboratory test results

  • History of coagulopathies, bleeding disorders, or blood dyscrasias

  • Current suicidal risk, in the opinion of the Investigator

  • Unexplained syncope during the 6 months prior to screening or with presyncopal and/or syncopal symptoms during orthostatic challenge testing

  • Current smoker or user of tobacco or nicotine-containing products or subjects who have smoked or used tobacco or nicotine-containing products within 3 months prior to first study drug administration

  • Suspicion of or presence of a clinically relevant history of or current alcohol and/or other substance abuse or addiction.

  • Alcohol consumption of >14 units per week for males and females

  • Positive urine alcohol test or urine drug screen at screening or Day -1 of any treatment period

  • Hormone replacement therapy if postmenopausal status cannot be ascertained from medical history or FSH levels

  • Clinically relevant deviation from normal in the physical examination including vital signs, as determined by the investigator

  • Positive result for HIV 1, HIV 2, hepatitis C virus antibody, or hepatitis B core (HBc) antibody.

  • Participation in an investigational drug or device study within 4 weeks or 5 times the elimination half-life, whichever is longer, prior to first dosing, or within 5 months prior to first administration of study drug in case of a study with a biological, as calculated from the day of Follow-up visit from the previous study

  • Donation of blood or plasma or significant blood loss within 3 months prior to screening

  • Dietary restrictions that would prohibit the consumption of standardized meals or the highfat, high-calorie meal planned for this study

  • Use of any prohibited medications or food before study start or subjects who do not agree to refrain from consuming prohibited medications or food during the study

  • Conditions requiring concomitant medication during the study (including for dental conditions).

  • Any prescribed systemic or topical medication within 4 weeks (or within 5 times the elimination half-life of the medication, whichever is longer) of the first administration of study drug

  • Used any nonprescribed systemic or topical medication or herbal remedies within 7 days before the first study drug administration

  • Received any medications known to chronically alter drug absorption or elimination processes within 4 weeks before the first administration of study drug

  • Use of any drugs or substances, including herbal treatments such as St John's wort, that are known to be substrates, inducers, or inhibitors of CYP3A4 within 4 weeks before the first administration of study drug

  • Use of any drugs or substances, including herbal treatments, such as fluoxetine, fluvoxamine, aspirin, norethisterone, rifampicin, etc that are known to be substrates, inducers, or inhibitors of CYP2C19 within 4 weeks before the first administration of study drug

  • Subjects under judicial supervision, guardianship, or curatorship

  • Poor venous access for blood sampling

  • Participants who are intolerant to sucrose

  • Previous exposure to balovaptan

Contacts and Locations

Locations

Site City State Country Postal Code
1 PRA International Clinical Pharmacology Center (EDS US Clinic) Lenexa Kansas United States 66219

Sponsors and Collaborators

  • Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT04156646
Other Study ID Numbers:
  • WP41047
First Posted:
Nov 7, 2019
Last Update Posted:
Mar 16, 2021
Last Verified:
Feb 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Autism Spectrum Disorder
Esomeprazole

Study Results

Participant Flow

Recruitment Details Screening was conducted between Day -28 and Day -2.
Pre-assignment Detail
Arm/Group Title Treatment Sequence ABC Treatment Sequence BAC
Arm/Group Description Participants were randomized to ABC sequence on Day 1 of Period 1 with the treatments being as follows: Treatment A: 20 mg balovaptan administered as a single oral dose following consumption of high-fat, high-calorie meal Treatment B: 20 mg balovaptan administered as a single oral dose after a ≥10-hour fast Treatment C: 40 mg esomeprazole administered once daily (QD) for 6 days and with a single dose of balovaptan 20 mg in the fasted state 1 hour after the fifth esomeprazole dose Participants were randomized to BAC sequence on Day 1 of Period 1 with the treatments being as follows: Treatment B: 20 mg balovaptan administered as a single oral dose after a ≥10-hour fast Treatment A: 20 mg balovaptan administered as a single oral dose following consumption of high-fat, high-calorie meal Treatment C: 40 mg esomeprazole administered once daily (QD) for 6 days and with a single dose of balovaptan 20 mg in the fasted state 1 hour after the fifth esomeprazole dose
Period Title: Treatment Period 1 (6 Days)
STARTED 8 8
COMPLETED 8 8
NOT COMPLETED 0 0
Period Title: Treatment Period 1 (6 Days)
STARTED 8 8
COMPLETED 8 8
NOT COMPLETED 0 0
Period Title: Treatment Period 1 (6 Days)
STARTED 8 8
COMPLETED 8 8
NOT COMPLETED 0 0
Period Title: Treatment Period 1 (6 Days)
STARTED 8 8
COMPLETED 8 8
NOT COMPLETED 0 0
Period Title: Treatment Period 1 (6 Days)
STARTED 8 8
COMPLETED 8 7
NOT COMPLETED 0 1

Baseline Characteristics

Arm/Group Title Treatment Sequence ABC Treatment Sequence BAC Total
Arm/Group Description Participants were randomized to ABC sequence on Day 1 of Period 1 with the treatments being as follows: Treatment A: 20 mg balovaptan administered as a single oral dose following consumption of high-fat, high-calorie meal Treatment B: 20 mg balovaptan administered as a single oral dose after a ≥10-hour fast Treatment C: 40 mg esomeprazole administered once daily (QD) for 6 days and with a single dose of balovaptan 20 mg in the fasted state 1 hour after the fifth esomeprazole dose Participants were randomized to BAC sequence on Day 1 of Period 1 with the treatments being as follows: Treatment B: 20 mg balovaptan administered as a single oral dose after a ≥10-hour fast Treatment A: 20 mg balovaptan administered as a single oral dose following consumption of high-fat, high-calorie meal Treatment C: 40 mg esomeprazole administered once daily (QD) for 6 days and with a single dose of balovaptan 20 mg in the fasted state 1 hour after the fifth esomeprazole dose Total of all reporting groups
Overall Participants 8 8 16
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
8
100%
8
100%
16
100%
>=65 years
0
0%
0
0%
0
0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
39.3
(11.96)
47.1
(13.26)
43.2
(12.9)
Sex: Female, Male (Count of Participants)
Female
4
50%
1
12.5%
5
31.3%
Male
4
50%
7
87.5%
11
68.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
1
12.5%
1
12.5%
2
12.5%
Not Hispanic or Latino
7
87.5%
7
87.5%
14
87.5%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
3
37.5%
4
50%
7
43.8%
White
5
62.5%
3
37.5%
8
50%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
1
12.5%
1
6.3%

Outcome Measures

1. Primary Outcome
Title Maximum Plasma Concentration (Cmax) of Balovaptan
Description Maximum plasma concentration of Balovaptan is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
74.83
(42.6)
97.44
(44.6)
79.67
(38.3)
2. Primary Outcome
Title Mean Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Balovaptan
Description Area under the plasma concentration-time curve (time 0 to infinity) of Balovaptan is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
For one participant with Balovaptan 20 mg Fasted+ Esomeprazole 40 mg Fasted, AUC(0-inf)%extrap was > 20%, so AUC(0-inf) and T1/2 were not included in summary statistics.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 15
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
1736.7
(51.3)
1705.7
(55.9)
1820.0
(46.9)
3. Primary Outcome
Title Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of Balovaptan
Description Area under the plasma concentration-time curve of Balovaptan from time 0 to 24 hours post-dose is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
935.2
(31.7)
945.2
(30.8)
965.0
(30.7)
4. Primary Outcome
Title Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Balovaptan
Description Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of Balovaptan is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
1671.0
(50.2)
1636.1
(53.3)
1650.9
(48.3)
5. Primary Outcome
Title Time to Reach Cmax in Plasma (Tmax) of Balovaptan
Description Time to maximum plasma concentration of Balovaptan is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Median (Full Range) [h]
4.50
1.00
1.75
6. Primary Outcome
Title Last Quantifiable Concentration (Clast) of Balovaptan
Description Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
1.693
(45.2)
1.745
(57.3)
2.253
(142.8)
7. Primary Outcome
Title Time To the Last Quantifiable Concentration (Tlast) of Balovaptan
Description Time to last quantifiable concentration is based on last detectable concentration in the time curve.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [h]
115.86
(33.4)
113.79
(35.0)
103.58
(41.0)
8. Primary Outcome
Title Time Between Dosing and Time of First Balovaptan Plasma Concentration (Tlag)
Description Time between dosing and time of first balovaptan plasma concentration is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Median (Full Range) [h]
0.2500
0.2500
0.2500
9. Primary Outcome
Title Apparent Clearance (Cl/F) of Balovaptan
Description Apparent clearance is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [L/h]
11.51
(35.7)
11.73
(36.3)
11.26
(32.2)
10. Primary Outcome
Title Apparent Volume of Distribution (Vd/F) of Balovaptan
Description Apparent volume of distribution is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [L]
422.7
(28.7)
422.5
(33.4)
429.4
(18.5)
11. Primary Outcome
Title Terminal Elimination Phase Half-Life (T1/2) of Balovaptan
Description Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
For one participant with Balovaptan 20 mg Fasted+ Esomeprazole 40 mg Fasted, AUC(0-inf)%extrap was > 20%, so AUC(0-inf) and T1/2 were not included in summary statistics.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 15
Geometric Mean (Geometric Coefficient of Variation) [h]
25.44
(40.0)
24.98
(47.0)
27.26
(40.9)
12. Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of M2 Metabolite
Description Maximum plasma concentration of M2 Metabolite is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
11.27
(27.0)
11.44
(30.8)
11.68
(30.1)
13. Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of M3 Metabolite
Description Maximum plasma concentration of M3 Metabolite is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
15.96
(37.0)
16.91
(40.8)
16.85
(32.3)
14. Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Esomeprazole
Description Maximum plasma concentration of Esomeprazole is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units
Time Frame Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
1255.2
(36.9)
15. Secondary Outcome
Title Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M2 Metabolite
Description Area under the plasma concentration-time curve (time 0 to infinity) of M2 Metabolite is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
For one participant (Balovaptan 20 mg Fasted, Balovaptan 20 mg Fasted + Esomeprazole) AUC(0-inf)%extrap was > 20%, so AUC(0-inf) was not included in summary statistics. For one participant in Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fastedthere was no terminal phase, so AUC(0-inf) could not be calculated. One participant was discontinued in Period 3 with Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted after withdrawal of consent.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 15 14
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
987.3
(27.5)
998.5
(22.7)
1087.7
(21.9)
16. Secondary Outcome
Title Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M3 Metabolite
Description Area under the plasma concentration-time curve (time 0 to infinity) of M3 Metabolite is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
Balovaptan 20 mg Fed: 3 participants were exluded from the analysis due to AUC(0-inf)%extrap > 20% Balovaptan 20 mg Fasted: 3 participants were exluded from the analysis due to AUC(0-inf)%extrap > 20% Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted: 4 participants were exluded from the analysis due to AUC(0-inf)%extrap > 20%. One additional participant was discontinued in Period 3 with Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted after withdrawal of consent.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 13 13 11
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
1552.9
(26.2)
1590.0
(26.9)
1723.2
(26.5)
17. Secondary Outcome
Title Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Esomeprazole
Description Area under the plasma concentration-time curve (time 0 to infinity) of Esomeprazole is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.
Time Frame Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose

Outcome Measure Data

Analysis Population Description
3 participants were excluded from the analysis due to missing data. For one of those the value was excluded due to AUC(0-inf)%extrap > 20%.
Arm/Group Title Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 13
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
4570.1
(48.7)
18. Secondary Outcome
Title Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M2 Metabolite
Description Area under the plasma concentration-time curve of M2 Metabolite from time 0 to 24 hours post-dose is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
150.6
(38.3)
180.1
(39.5)
182.2
(35.9)
19. Secondary Outcome
Title Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M3 Metabolite
Description Area under the plasma concentration-time curve of M3 Metabolite from time 0 to 24 hours post-dose is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
269.8
(40.9)
325.1
(42.0)
325.5
(34.1)
20. Secondary Outcome
Title Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M2 Metabolite
Description Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of M2 Metabolite is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
897.6
(27.2)
869.4
(26.9)
873.9
(32.8)
21. Secondary Outcome
Title Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M3 Metabolite
Description Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of M3 Metabolite is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
1389.6
(23.9)
1462.8
(29.3)
1384.3
(35.6)
22. Secondary Outcome
Title Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Esomeprazole
Description Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of Esomeprazole is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
4014.9
(42.9)
23. Secondary Outcome
Title Time to Reach Cmax in Plasma (Tmax) of M2 Metabolite
Description Time to maximum plasma concentration of M2 Metabolite is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Median (Full Range) [h]
36.00
24.03
36.00
24. Secondary Outcome
Title Time to Reach Cmax in Plasma (Tmax) of M3 Metabolite
Description Time to maximum plasma concentration of M3 Metabolite is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Median (Full Range) [h]
20.01
24.02
16.00
25. Secondary Outcome
Title Time to Reach Cmax in Plasma (Tmax) of Esomeprazole
Description Time to maximum plasma concentration of Esomeprazole is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16
Median (Full Range) [h]
2.00
26. Secondary Outcome
Title Last Quantifiable Concentration (Clast) of M2 Metabolite
Description Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
1.515
(30.0)
1.739
(29.4)
1.682
(82.8)
27. Secondary Outcome
Title Last Quantifiable Concentration (Clast) of M3 Metabolite
Description Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
2.211
(46.2)
2.279
(55.4)
2.837
(82.1)
28. Secondary Outcome
Title Last Quantifiable Concentration (Clast) of Esomeprazole
Description Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
133.3
(78.8)
29. Secondary Outcome
Title Time To the Last Quantifiable Concentration (Tlast) of M2 Metabolite
Description Time to last quantifiable concentration is based on last detectable concentration in the time curve.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [h]
155.3
(21.2)
142.4
(25.2)
142.4
(29.5)
30. Secondary Outcome
Title Time To the Last Quantifiable Concentration (Tlast) of M3 Metabolite
Description Time to last quantifiable concentration is based on last detectable concentration in the time curve.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [h]
192.0
(0.0)
192.0
(0.0)
168.7
(23.1)
31. Secondary Outcome
Title Time To the Last Quantifiable Concentration (Tlast) of Esomeprazole
Description Time to last quantifiable concentration is based on last detectable concentration in the time curve.
Time Frame Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16
Geometric Mean (Geometric Coefficient of Variation) [h]
8.002
(0.1)
32. Secondary Outcome
Title Terminal Elimination Phase Half-Life (T1/2) of M2 Metabolite
Description Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
For one participant in Balovaptan 20 mg Fasted and one participant in Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted AUC(0-inf)%extrap was > 20%, so T1/2 were not included in summary statistics. For one additional participant in Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted there was no terminal phase, so AUC(0-inf) and T1/2 could not be calculated.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 15 14
Geometric Mean (Geometric Coefficient of Variation) [h]
38.99
(29.2)
37.81
(30.7)
39.19
(22.7)
33. Secondary Outcome
Title Terminal Elimination Phase Half-Life (T1/2) of M3 Metabolite
Description Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
For 3 subjects in Balovaptan 20 mg Fed, 3 subjects in Balovaptan 20 mg Fasted and 4 subjects in Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted AUC(0-inf)%extrap was > 20%, so AUC(0-inf) were not included in summary statistics.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 13 13 11
Geometric Mean (Geometric Coefficient of Variation) [h]
57.40
(17.3)
59.30
(17.6)
57.81
(19.2)
34. Secondary Outcome
Title Terminal Elimination Phase Half-Life (T1/2) of Esomeprazole
Description Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose

Outcome Measure Data

Analysis Population Description
For one participant AUC(0-inf)%extrap was > 20%, so T1/2 was not included in summary statistics. For 2 participants, there was no terminal phase, so T1/2 could not be calculated.
Arm/Group Title Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 13
Geometric Mean (Geometric Coefficient of Variation) [h]
1.590
(29.2)
35. Secondary Outcome
Title Percentage of Patricipants With Adverse Events (AEs)
Description
Time Frame Randomization to end of study (up to approximately 7 weeks)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Count of Participants [Participants]
1
12.5%
1
12.5%
1
6.3%
36. Primary Outcome
Title Terminal Phase Rate Constant (λz) of Balovaptan
Description Terminal phase rate constant is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Geometric Mean (Geometric Coefficient of Variation) [/h]
0.0272
(33.3)
0.0278
(37.5)
0.0263
(30.3)
37. Secondary Outcome
Title Terminal Phase Rate Constant (λz) of M2 Metabolite
Description Terminal phase rate constant is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
For one participant there was no terminal phase, so they are excluded form the analysis.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 15
Geometric Mean (Geometric Coefficient of Variation) [/h]
0.0178
(30.3)
0.0174
(31.9)
0.0171
(25.5)
38. Secondary Outcome
Title Terminal Phase Rate Constant (λz) of M3 Metabolite
Description Terminal phase rate constant is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
For one participant there was no terminal phase, so they are excluded form the analysis.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 15
Geometric Mean (Geometric Coefficient of Variation) [/h]
0.0112
(22.1)
0.0107
(24.8)
0.0107
(25.2)
39. Secondary Outcome
Title Terminal Phase Rate Constant (λz) of Esomeprazole
Description Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.
Time Frame Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose

Outcome Measure Data

Analysis Population Description
For two participants there was no terminal phase, so they are excluded form the analysis.
Arm/Group Title Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 14
Geometric Mean (Geometric Coefficient of Variation) [/h]
0.4197
(30.1)
40. Primary Outcome
Title Plasma Concentrations of Balovaptan
Description Amount of Balovaptan in a given volume of plasma.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
Number of analyzed participants reflects number of participants whose samples were available at given timepoint.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Predose
NA
(NA)
NA
(NA)
NA
(NA)
0.25 Hrs Postdose
3.90
(246.8)
2.46
(136.0)
NA
(NA)
0.5 Hrs Postdose
8.89
(235.7)
21.26
(117.5)
8.40
(129.8)
1 Hrs Postdose
17.76
(113.0)
63.58
(60.9)
44.78
(70.8)
1.5 Hrs Postdose
20.08
(88.2)
66.54
(47.4)
49.82
(52.7)
2 Hrs Postdose
27.47
(77.0)
70.75
(32.9)
62.24
(37.0)
2.5 Hrs Postdose
32.90
(73.0)
66.40
(33.4)
63.44
(32.1)
3 Hrs Postdose
41.92
(73.6)
63.60
(29.7)
66.26
(29.8)
3.5 Hrs Postdose
45.68
(60.4)
60.63
(31.2)
64.70
(34.5)
4 Hrs Postdose
51.84
(50.2)
59.58
(27.9)
63.95
(31.5)
5 Hrs Postdose
60.59
(36.5)
59.56
(27.4)
61.45
(35.4)
6 Hrs Postdose
56.91
(34.6)
49.69
(28.3)
54.51
(31.1)
8 Hrs Postdose
51.07
(30.7)
44.58
(30.0)
48.05
(30.5)
12 Hrs Postdose
39.18
(27.4)
34.74
(32.9)
35.91
(31.8)
16 Hrs Postdose
33.17
(38.5)
28.88
(37.5)
30.85
(37.1)
24 Hrs Postdose
25.43
(42.7)
22.95
(43.6)
25.95
(37.2)
36 Hrs Postdose
14.94
(57.1)
13.92
(55.4)
15.13
(50.1)
48 Hrs Postdose
9.75
(70.5)
10.70
(7.376)
12.15
(6.794)
72 Hrs Postdose
4.47
(90.2)
4.28
(97.8)
5.04
(64.0)
96 Hrs Postdose
2.68
(112.0)
2.86
(125.0)
2.98
(91.4)
144 Hrs Postdose
2.38
(186.5)
2.45
(204.4)
2.57
(198.5)
192 Hrs Postdose
NA
(NA)
NA
(NA)
NA
(NA)
41. Secondary Outcome
Title Plasma Concentrations of M2 Analyte
Description Amount of M2 Analyte in a given volume of plasma.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
Number of analyzed participants reflects number of participants whose samples were available at given timepoint.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Predose
NA
(NA)
NA
(NA)
NA
(NA)
0.25 Hrs Postdose
NA
(NA)
NA
(NA)
NA
(NA)
0.5 Hrs Postdose
NA
(NA)
NA
(NA)
NA
(NA)
1 Hrs Postdose
NA
(NA)
3.081
(62.2)
2.649
(95.5)
1.5 Hrs Postdose
NA
(NA)
3.421
(57.2)
2.690
(72.6)
2 Hrs Postdose
2.021
(97.7)
3.637
(45.6)
3.019
(54.9)
2.5 Hrs Postdose
2.236
(83.3)
3.724
(48.8)
3.502
(46.4)
3 Hrs Postdose
2.714
(80.0)
4.293
(49.9)
3.878
(43.2)
3.5 Hrs Postdose
2.780
(75.7)
4.724
(49.2)
4.217
(44.5)
4 Hrs Postdose
3.208
(65.5)
4.860
(49.1)
4.749
(41.1)
5 Hrs Postdose
3.756
(60.5)
5.696
(47.9)
5.471
(44.8)
6 Hrs Postdose
4.158
(50.9)
5.797
(50.0)
5.775
(39.8)
8 Hrs Postdose
5.223
(48.9)
6.550
(46.6)
6.512
(40.8)
12 Hrs Postdose
6.921
(40.4)
7.889
(39.5)
8.426
(42.9)
16 Hrs Postdose
8.384
(39.7)
9.207
(40.9)
9.563
(34.2)
24 Hrs Postdose
10.123
(29.4)
10.928
(30.9)
10.887
(33.0)
36 Hrs Postdose
10.509
(29.6)
10.519
(27.4)
11.409
(26.9)
48 Hrs Postdose
9.383
(28.2)
9.134
(25.8)
10.191
(26.8)
72 Hrs Postdose
6.576
(30.7)
5.998
(27.5)
27.5
(23.5)
96 Hrs Postdose
4.050
(41.6)
3.748
(32.9)
4.450
(27.5)
144 Hrs Postdose
2.033
(64.7)
2.139
(71.9)
2.107
(45.2)
192 Hrs Postdose
NA
(NA)
NA
(NA)
NA
(NA)
42. Secondary Outcome
Title Plasma Concentrations of M3 Analyte
Description Amount of M3 Analyte in a given volume of plasma.
Time Frame Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Outcome Measure Data

Analysis Population Description
Number of analyzed participants reflects number of participants whose samples were available at given timepoint.
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16 16 16
Predose
NA
(NA)
NA
(NA)
NA
(NA)
0.25 Hrs Postdose
NA
(NA)
NA
(NA)
NA
(NA)
0.5 Hrs Postdose
NA
(NA)
5.006
(118.0)
3.172
(127.1)
1 Hrs Postdose
2.347
(138.4)
7.812
(60.6)
5.556
(78.9)
1.5 Hrs Postdose
3.787
(95.1)
8.928
(59.6)
6.705
(62.6)
2 Hrs Postdose
5.211
(83.0)
10.157
(46.8)
8.859
(55.8)
2.5 Hrs Postdose
5.520
(83.5)
10.539
(47.9)
9.853
(45.8)
3 Hrs Postdose
6.616
(85.9)
10.980
(48.6)
10.887
(39.4)
3.5 Hrs Postdose
5.985
(78.0)
11.369
(50.8)
11.316
(41.2)
4 Hrs Postdose
6.408
(71.4)
12.160
(50.8)
11.969
(38.0)
5 Hrs Postdose
8.901
(58.8)
13.241
(41.5)
12.998
(46.7)
6 Hrs Postdose
9.691
(59.8)
12.831
(47.9)
13.442
(39.6)
8 Hrs Postdose
11.157
(47.8)
13.875
(48.4)
13.762
(40.4)
12 Hrs Postdose
12.697
(5.7063)
14.296
(39.7)
14.287
(36.3)
16 Hrs Postdose
14.113
(40.9)
15.145
(41.6)
15.049
(30.1)
24 Hrs Postdose
14.388
(33.4)
15.061
(39.7)
16.092
(29.9)
36 Hrs Postdose
13.626
(26.4)
14.148
(29.7)
13.793
(27.7)
48 Hrs Postdose
11.665
(26.4)
11.470
(29.0)
12.966
(27.3)
72 Hrs Postdose
8.108
(28.3)
8.129
(31.3)
9.023
(25.2)
96 Hrs Postdose
6.066
(31.6)
6.111
(42.4)
6.653
(34.1)
144 Hrs Postdose
3.525
(45.5)
3.747
(45.7)
3.957
(45.2)
192 Hrs Postdose
2.211
(46.2)
2.279
(55.4)
2.569
(54.2)
43. Secondary Outcome
Title Plasma Concentrations of Esomeprazole
Description Amount of Esomeprazole in a given volume of plasma.
Time Frame Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose

Outcome Measure Data

Analysis Population Description
Number of analyzed participants reflects number of participants whose samples were available at given timepoint.
Arm/Group Title Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Measure Participants 16
Predose
NA
(NA)
0.25 Hrs Postdose
NA
(NA)
0.5 Hrs Postdose
NA
(NA)
1 Hrs Postdose
171.8
(171.5)
1.5 Hrs Postdose
242.6
(102.8)
2 Hrs Postdose
697.1
(66.2)
3 Hrs Postdose
984.4
(36.1)
4 Hrs Postdose
770.7
(34.7)
6 Hrs Postdose
336.6
(59.8)
8 Hrs Postdose
133.3
(78.8)

Adverse Events

Time Frame From baseline to end of study (up to approximately 7 weeks)
Adverse Event Reporting Description
Arm/Group Title Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Arm/Group Description Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A). Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B) Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state.
All Cause Mortality
Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/16 (0%) 0/16 (0%) 0/16 (0%)
Serious Adverse Events
Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/16 (0%) 0/16 (0%) 0/16 (0%)
Other (Not Including Serious) Adverse Events
Balovaptan 20 mg Fed Balovaptan 20 mg Fasted Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/16 (6.3%) 1/16 (6.3%) 1/16 (6.3%)
Eye disorders
Eye Pain 0/16 (0%) 0 1/16 (6.3%) 1 0/16 (0%) 0
Infections and infestations
Gastroenteritis 0/16 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
Injury, poisoning and procedural complications
Tooth fracture 0/16 (0%) 0 0/16 (0%) 0 1/16 (6.3%) 1
Nervous system disorders
Headache 1/16 (6.3%) 1 0/16 (0%) 0 0/16 (0%) 0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

Name/Title Medical Communications
Organization Hoffmann-La Roche
Phone 800 821-8590
Email genentech@druginfo.com
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT04156646
Other Study ID Numbers:
  • WP41047
First Posted:
Nov 7, 2019
Last Update Posted:
Mar 16, 2021
Last Verified:
Feb 1, 2021