Skip to main content
OpenTrials
Completed

NCT Number: NCT04156646

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Autism Spectrum Disorder Child Development Disorders, Pervasive Mental Disorders Neurodevelopmental Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

PRA International Clinical Pharmacology Center (EDS US Clinic)

Lenexa, Kansas, 66219, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Balovaptan

Drug

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)

Esomeprazole

Drug

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

Primary outcomes

  1. Maximum Plasma Concentration (Cmax) of Balovaptan

    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

    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

    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

    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

    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

    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

    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

    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

    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

    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

    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

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

  7. Time To the Last Quantifiable Concentration (Tlast) of Balovaptan

    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

    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)

    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

    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

    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

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

  10. Apparent Volume of Distribution (Vd/F) of Balovaptan

    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

    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

    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

    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

    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

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

  13. Plasma Concentrations of Balovaptan

    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

    Amount of Balovaptan in a given volume of plasma.

Secondary outcomes

  1. Maximum Plasma Concentration (Cmax) of M2 Metabolite

    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

    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

    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

    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

    Time frame: 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

    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

    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

    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

    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

    Time frame: 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

    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

    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

    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

    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

    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

    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

    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

    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

    Time frame: 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

    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

    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

    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

    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

    Time frame: 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

    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

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

  16. Last Quantifiable Concentration (Clast) of M3 Metabolite

    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

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

  17. Last Quantifiable Concentration (Clast) of Esomeprazole

    Time frame: 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

    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

    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

    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

    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

    Time frame: 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

    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

    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

    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

    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

    Time frame: 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)

    Time frame: Randomization to end of study (up to approximately 7 weeks)

  25. Terminal Phase Rate Constant (λz) of M2 Metabolite

    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

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

  26. Terminal Phase Rate Constant (λz) of M3 Metabolite

    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

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

  27. Terminal Phase Rate Constant (λz) of Esomeprazole

    Time frame: 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

    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

    Amount of M2 Analyte in a given volume of plasma.

  29. Plasma Concentrations of M3 Analyte

    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

    Amount of M3 Analyte in a given volume of plasma.

  30. Plasma Concentrations of Esomeprazole

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2019
Study completion
2020
First posted
Nov 7, 2019
Registry last updated
Mar 16, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.