Clinical trial NCT04156646: A Study to Investigate the Effect of Esomeprazole and the Effect of Food on the Pharmacokinetics of Balovaptan in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Autism Spectrum Disorder
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-11-07
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Balovaptan
timeFrame: 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
measure: Mean Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Balovaptan
timeFrame: 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
measure: Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of Balovaptan
timeFrame: 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
measure: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Balovaptan
timeFrame: 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
measure: Time to Reach Cmax in Plasma (Tmax) of Balovaptan
timeFrame: 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
measure: Last Quantifiable Concentration (Clast) of Balovaptan
timeFrame: 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
measure: Time To the Last Quantifiable Concentration (Tlast) of Balovaptan
timeFrame: 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
measure: Time Between Dosing and Time of First Balovaptan Plasma Concentration (Tlag)
timeFrame: 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
measure: Apparent Clearance (Cl/F) of Balovaptan
timeFrame: 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
measure: Apparent Volume of Distribution (Vd/F) of Balovaptan
timeFrame: 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
measure: Terminal Elimination Phase Half-Life (T1/2) of Balovaptan
timeFrame: 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
measure: Terminal Phase Rate Constant (λz) of Balovaptan
timeFrame: 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
measure: Plasma Concentrations of Balovaptan
timeFrame: 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
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of M2 Metabolite
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of M3 Metabolite
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of Esomeprazole
timeFrame: Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
measure: Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M2 Metabolite
timeFrame: 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
measure: Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M3 Metabolite
timeFrame: 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
measure: Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Esomeprazole
timeFrame: Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
measure: Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M2 Metabolite
timeFrame: 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
measure: Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M3 Metabolite
timeFrame: 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
measure: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M2 Metabolite
timeFrame: 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
measure: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M3 Metabolite
timeFrame: 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
measure: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Esomeprazole
timeFrame: Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
measure: Time to Reach Cmax in Plasma (Tmax) of M2 Metabolite
timeFrame: 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
measure: Time to Reach Cmax in Plasma (Tmax) of M3 Metabolite
timeFrame: 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
measure: Time to Reach Cmax in Plasma (Tmax) of Esomeprazole
timeFrame: Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
measure: Last Quantifiable Concentration (Clast) of M2 Metabolite
timeFrame: 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
measure: Last Quantifiable Concentration (Clast) of M3 Metabolite
timeFrame: 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
measure: Last Quantifiable Concentration (Clast) of Esomeprazole
timeFrame: Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
measure: Time To the Last Quantifiable Concentration (Tlast) of M2 Metabolite
timeFrame: 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
measure: Time To the Last Quantifiable Concentration (Tlast) of M3 Metabolite
timeFrame: 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
measure: Time To the Last Quantifiable Concentration (Tlast) of Esomeprazole
timeFrame: Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
measure: Terminal Elimination Phase Half-Life (T1/2) of M2 Metabolite
timeFrame: 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
measure: Terminal Elimination Phase Half-Life (T1/2) of M3 Metabolite
timeFrame: 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
measure: Terminal Elimination Phase Half-Life (T1/2) of Esomeprazole
timeFrame: Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
measure: Percentage of Patricipants With Adverse Events (AEs)
timeFrame: Randomization to end of study (up to approximately 7 weeks)
measure: Terminal Phase Rate Constant (λz) of M2 Metabolite
timeFrame: 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
measure: Terminal Phase Rate Constant (λz) of M3 Metabolite
timeFrame: 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
measure: Terminal Phase Rate Constant (λz) of Esomeprazole
timeFrame: Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
measure: Plasma Concentrations of M2 Analyte
timeFrame: 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
measure: Plasma Concentrations of M3 Analyte
timeFrame: 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
measure: Plasma Concentrations of Esomeprazole
timeFrame: Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
Other outcomes:
Locations:
city: Lenexa
country: United States
facility: PRA International Clinical Pharmacology Center (EDS US Clinic)
state: Kansas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: