Autism Spectrum Disorder
Conditions
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.
Interventions
DRUGBalovaptan
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)
DRUGEsomeprazole
Esomeprazole will be administered once daily for 6 days and with a single dose of balovaptan 1 hour after the fifth esomeprazole dose
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Percentage of Patricipants With Adverse Events (AEs) | Randomization to end of study (up to approximately 7 weeks) | — |
| 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. |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Screening was conducted between Day -28 and Day -2.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence ABC 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 | 8 |
| Treatment Sequence BAC 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 | 8 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 3 (6 Days) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Treatment Sequence ABC | Treatment Sequence BAC | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 16 Participants |
| Age, Continuous | 39.3 Years STANDARD_DEVIATION 11.96 | 47.1 Years STANDARD_DEVIATION 13.26 | 43.2 Years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 7 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 1 / 16 | 1 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Apparent Clearance (Cl/F) of Balovaptan
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Apparent Clearance (Cl/F) of Balovaptan | 11.51 L/h | Geometric Coefficient of Variation 35.7 |
| Balovaptan 20 mg Fasted | Apparent Clearance (Cl/F) of Balovaptan | 11.73 L/h | Geometric Coefficient of Variation 36.3 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Apparent Clearance (Cl/F) of Balovaptan | 11.26 L/h | Geometric Coefficient of Variation 32.2 |
Primary
Apparent Volume of Distribution (Vd/F) of Balovaptan
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Apparent Volume of Distribution (Vd/F) of Balovaptan | 422.7 L | Geometric Coefficient of Variation 28.7 |
| Balovaptan 20 mg Fasted | Apparent Volume of Distribution (Vd/F) of Balovaptan | 422.5 L | Geometric Coefficient of Variation 33.4 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Apparent Volume of Distribution (Vd/F) of Balovaptan | 429.4 L | Geometric Coefficient of Variation 18.5 |
Primary
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of Balovaptan
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of Balovaptan | 935.2 h*ng/mL | Geometric Coefficient of Variation 31.7 |
| Balovaptan 20 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of Balovaptan | 945.2 h*ng/mL | Geometric Coefficient of Variation 30.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of Balovaptan | 965.0 h*ng/mL | Geometric Coefficient of Variation 30.7 |
Primary
Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Balovaptan
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Balovaptan | 1671.0 h*ng/mL | Geometric Coefficient of Variation 50.2 |
| Balovaptan 20 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Balovaptan | 1636.1 h*ng/mL | Geometric Coefficient of Variation 53.3 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Balovaptan | 1650.9 h*ng/mL | Geometric Coefficient of Variation 48.3 |
Primary
Last Quantifiable Concentration (Clast) of Balovaptan
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Last Quantifiable Concentration (Clast) of Balovaptan | 1.693 ng/mL | Geometric Coefficient of Variation 45.2 |
| Balovaptan 20 mg Fasted | Last Quantifiable Concentration (Clast) of Balovaptan | 1.745 ng/mL | Geometric Coefficient of Variation 57.3 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Last Quantifiable Concentration (Clast) of Balovaptan | 2.253 ng/mL | Geometric Coefficient of Variation 142.8 |
Primary
Maximum Plasma Concentration (Cmax) of Balovaptan
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Maximum Plasma Concentration (Cmax) of Balovaptan | 74.83 ng/mL | Geometric Coefficient of Variation 42.6 |
| Balovaptan 20 mg Fasted | Maximum Plasma Concentration (Cmax) of Balovaptan | 97.44 ng/mL | Geometric Coefficient of Variation 44.6 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Maximum Plasma Concentration (Cmax) of Balovaptan | 79.67 ng/mL | Geometric Coefficient of Variation 38.3 |
Primary
Mean Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Balovaptan
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Mean Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Balovaptan | 1736.7 h*ng/mL | Geometric Coefficient of Variation 51.3 |
| Balovaptan 20 mg Fasted | Mean Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Balovaptan | 1705.7 h*ng/mL | Geometric Coefficient of Variation 55.9 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Mean Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Balovaptan | 1820.0 h*ng/mL | Geometric Coefficient of Variation 46.9 |
Primary
Plasma Concentrations of Balovaptan
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
Population: Number of analyzed participants reflects number of participants whose samples were available at given timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 24 Hrs Postdose | 25.43 ng/mL | Geometric Coefficient of Variation 42.7 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 4 Hrs Postdose | 51.84 ng/mL | Geometric Coefficient of Variation 50.2 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 8 Hrs Postdose | 51.07 ng/mL | Geometric Coefficient of Variation 30.7 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 5 Hrs Postdose | 60.59 ng/mL | Geometric Coefficient of Variation 36.5 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 36 Hrs Postdose | 14.94 ng/mL | Geometric Coefficient of Variation 57.1 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 6 Hrs Postdose | 56.91 ng/mL | Geometric Coefficient of Variation 34.6 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 96 Hrs Postdose | 2.68 ng/mL | Geometric Coefficient of Variation 112 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 48 Hrs Postdose | 9.75 ng/mL | Geometric Coefficient of Variation 70.5 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 72 Hrs Postdose | 4.47 ng/mL | Geometric Coefficient of Variation 90.2 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 144 Hrs Postdose | 2.38 ng/mL | Geometric Coefficient of Variation 186.5 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 192 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 12 Hrs Postdose | 39.18 ng/mL | Geometric Coefficient of Variation 27.4 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | Predose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 0.25 Hrs Postdose | 3.90 ng/mL | Geometric Coefficient of Variation 246.8 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 1.5 Hrs Postdose | 20.08 ng/mL | Geometric Coefficient of Variation 88.2 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 0.5 Hrs Postdose | 8.89 ng/mL | Geometric Coefficient of Variation 235.7 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 16 Hrs Postdose | 33.17 ng/mL | Geometric Coefficient of Variation 38.5 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 1 Hrs Postdose | 17.76 ng/mL | Geometric Coefficient of Variation 113 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 2.5 Hrs Postdose | 32.90 ng/mL | Geometric Coefficient of Variation 73 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 2 Hrs Postdose | 27.47 ng/mL | Geometric Coefficient of Variation 77 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 3 Hrs Postdose | 41.92 ng/mL | Geometric Coefficient of Variation 73.6 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Balovaptan | 3.5 Hrs Postdose | 45.68 ng/mL | Geometric Coefficient of Variation 60.4 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 0.5 Hrs Postdose | 21.26 ng/mL | Geometric Coefficient of Variation 117.5 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 3.5 Hrs Postdose | 60.63 ng/mL | Geometric Coefficient of Variation 31.2 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 24 Hrs Postdose | 22.95 ng/mL | Geometric Coefficient of Variation 43.6 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 192 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 4 Hrs Postdose | 59.58 ng/mL | Geometric Coefficient of Variation 27.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 3 Hrs Postdose | 63.60 ng/mL | Geometric Coefficient of Variation 29.7 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 2.5 Hrs Postdose | 66.40 ng/mL | Geometric Coefficient of Variation 33.4 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 5 Hrs Postdose | 59.56 ng/mL | Geometric Coefficient of Variation 27.4 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | Predose | NA ng/mL | — |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 12 Hrs Postdose | 34.74 ng/mL | Geometric Coefficient of Variation 32.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 6 Hrs Postdose | 49.69 ng/mL | Geometric Coefficient of Variation 28.3 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 8 Hrs Postdose | 44.58 ng/mL | Geometric Coefficient of Variation 30 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 36 Hrs Postdose | 13.92 ng/mL | Geometric Coefficient of Variation 55.4 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 1 Hrs Postdose | 63.58 ng/mL | Geometric Coefficient of Variation 60.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 0.25 Hrs Postdose | 2.46 ng/mL | Geometric Coefficient of Variation 136 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 48 Hrs Postdose | 10.70 ng/mL | Geometric Coefficient of Variation 7.376 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 144 Hrs Postdose | 2.45 ng/mL | Geometric Coefficient of Variation 204.4 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 2 Hrs Postdose | 70.75 ng/mL | Geometric Coefficient of Variation 32.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 72 Hrs Postdose | 4.28 ng/mL | Geometric Coefficient of Variation 97.8 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 96 Hrs Postdose | 2.86 ng/mL | Geometric Coefficient of Variation 125 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 1.5 Hrs Postdose | 66.54 ng/mL | Geometric Coefficient of Variation 47.4 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of Balovaptan | 16 Hrs Postdose | 28.88 ng/mL | Geometric Coefficient of Variation 37.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 36 Hrs Postdose | 15.13 ng/mL | Geometric Coefficient of Variation 50.1 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 1.5 Hrs Postdose | 49.82 ng/mL | Geometric Coefficient of Variation 52.7 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 8 Hrs Postdose | 48.05 ng/mL | Geometric Coefficient of Variation 30.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 12 Hrs Postdose | 35.91 ng/mL | Geometric Coefficient of Variation 31.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 16 Hrs Postdose | 30.85 ng/mL | Geometric Coefficient of Variation 37.1 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 24 Hrs Postdose | 25.95 ng/mL | Geometric Coefficient of Variation 37.2 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 72 Hrs Postdose | 5.04 ng/mL | Geometric Coefficient of Variation 64 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 144 Hrs Postdose | 2.57 ng/mL | Geometric Coefficient of Variation 198.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 192 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | Predose | NA ng/mL | — |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 0.25 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 0.5 Hrs Postdose | 8.40 ng/mL | Geometric Coefficient of Variation 129.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 2 Hrs Postdose | 62.24 ng/mL | Geometric Coefficient of Variation 37 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 2.5 Hrs Postdose | 63.44 ng/mL | Geometric Coefficient of Variation 32.1 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 3 Hrs Postdose | 66.26 ng/mL | Geometric Coefficient of Variation 29.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 3.5 Hrs Postdose | 64.70 ng/mL | Geometric Coefficient of Variation 34.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 4 Hrs Postdose | 63.95 ng/mL | Geometric Coefficient of Variation 31.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 5 Hrs Postdose | 61.45 ng/mL | Geometric Coefficient of Variation 35.4 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 6 Hrs Postdose | 54.51 ng/mL | Geometric Coefficient of Variation 31.1 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 1 Hrs Postdose | 44.78 ng/mL | Geometric Coefficient of Variation 70.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 48 Hrs Postdose | 12.15 ng/mL | Geometric Coefficient of Variation 6.794 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of Balovaptan | 96 Hrs Postdose | 2.98 ng/mL | Geometric Coefficient of Variation 91.4 |
Primary
Terminal Elimination Phase Half-Life (T1/2) of Balovaptan
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Terminal Elimination Phase Half-Life (T1/2) of Balovaptan | 25.44 h | Geometric Coefficient of Variation 40 |
| Balovaptan 20 mg Fasted | Terminal Elimination Phase Half-Life (T1/2) of Balovaptan | 24.98 h | Geometric Coefficient of Variation 47 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Terminal Elimination Phase Half-Life (T1/2) of Balovaptan | 27.26 h | Geometric Coefficient of Variation 40.9 |
Primary
Terminal Phase Rate Constant (λz) of Balovaptan
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Terminal Phase Rate Constant (λz) of Balovaptan | 0.0272 /h | Geometric Coefficient of Variation 33.3 |
| Balovaptan 20 mg Fasted | Terminal Phase Rate Constant (λz) of Balovaptan | 0.0278 /h | Geometric Coefficient of Variation 37.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Terminal Phase Rate Constant (λz) of Balovaptan | 0.0263 /h | Geometric Coefficient of Variation 30.3 |
Primary
Time Between Dosing and Time of First Balovaptan Plasma Concentration (Tlag)
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Balovaptan 20 mg Fed | Time Between Dosing and Time of First Balovaptan Plasma Concentration (Tlag) | 0.2500 h |
| Balovaptan 20 mg Fasted | Time Between Dosing and Time of First Balovaptan Plasma Concentration (Tlag) | 0.2500 h |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Time Between Dosing and Time of First Balovaptan Plasma Concentration (Tlag) | 0.2500 h |
Primary
Time to Reach Cmax in Plasma (Tmax) of Balovaptan
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Balovaptan 20 mg Fed | Time to Reach Cmax in Plasma (Tmax) of Balovaptan | 4.50 h |
| Balovaptan 20 mg Fasted | Time to Reach Cmax in Plasma (Tmax) of Balovaptan | 1.00 h |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Time to Reach Cmax in Plasma (Tmax) of Balovaptan | 1.75 h |
Primary
Time To the Last Quantifiable Concentration (Tlast) of Balovaptan
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Time To the Last Quantifiable Concentration (Tlast) of Balovaptan | 115.86 h | Geometric Coefficient of Variation 33.4 |
| Balovaptan 20 mg Fasted | Time To the Last Quantifiable Concentration (Tlast) of Balovaptan | 113.79 h | Geometric Coefficient of Variation 35 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Time To the Last Quantifiable Concentration (Tlast) of Balovaptan | 103.58 h | Geometric Coefficient of Variation 41 |
Secondary
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M2 Metabolite
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M2 Metabolite | 150.6 h*ng/mL | Geometric Coefficient of Variation 38.3 |
| Balovaptan 20 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M2 Metabolite | 180.1 h*ng/mL | Geometric Coefficient of Variation 39.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M2 Metabolite | 182.2 h*ng/mL | Geometric Coefficient of Variation 35.9 |
Secondary
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M3 Metabolite
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M3 Metabolite | 269.8 h*ng/mL | Geometric Coefficient of Variation 40.9 |
| Balovaptan 20 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M3 Metabolite | 325.1 h*ng/mL | Geometric Coefficient of Variation 42 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M3 Metabolite | 325.5 h*ng/mL | Geometric Coefficient of Variation 34.1 |
Secondary
Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Esomeprazole
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Esomeprazole | 4014.9 h*ng/mL | Geometric Coefficient of Variation 42.9 |
Secondary
Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M2 Metabolite
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M2 Metabolite | 897.6 h*ng/mL | Geometric Coefficient of Variation 27.2 |
| Balovaptan 20 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M2 Metabolite | 869.4 h*ng/mL | Geometric Coefficient of Variation 26.9 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M2 Metabolite | 873.9 h*ng/mL | Geometric Coefficient of Variation 32.8 |
Secondary
Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M3 Metabolite
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M3 Metabolite | 1389.6 h*ng/mL | Geometric Coefficient of Variation 23.9 |
| Balovaptan 20 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M3 Metabolite | 1462.8 h*ng/mL | Geometric Coefficient of Variation 29.3 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M3 Metabolite | 1384.3 h*ng/mL | Geometric Coefficient of Variation 35.6 |
Secondary
Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Esomeprazole
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Esomeprazole | 4570.1 h*ng/mL | Geometric Coefficient of Variation 48.7 |
Secondary
Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M2 Metabolite
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M2 Metabolite | 987.3 h*ng/mL | Geometric Coefficient of Variation 27.5 |
| Balovaptan 20 mg Fasted | Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M2 Metabolite | 998.5 h*ng/mL | Geometric Coefficient of Variation 22.7 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M2 Metabolite | 1087.7 h*ng/mL | Geometric Coefficient of Variation 21.9 |
Secondary
Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M3 Metabolite
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M3 Metabolite | 1552.9 h*ng/mL | Geometric Coefficient of Variation 26.2 |
| Balovaptan 20 mg Fasted | Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M3 Metabolite | 1590.0 h*ng/mL | Geometric Coefficient of Variation 26.9 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M3 Metabolite | 1723.2 h*ng/mL | Geometric Coefficient of Variation 26.5 |
Secondary
Last Quantifiable Concentration (Clast) of Esomeprazole
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Last Quantifiable Concentration (Clast) of Esomeprazole | 133.3 ng/mL | Geometric Coefficient of Variation 78.8 |
Secondary
Last Quantifiable Concentration (Clast) of M2 Metabolite
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Last Quantifiable Concentration (Clast) of M2 Metabolite | 1.515 ng/mL | Geometric Coefficient of Variation 30 |
| Balovaptan 20 mg Fasted | Last Quantifiable Concentration (Clast) of M2 Metabolite | 1.739 ng/mL | Geometric Coefficient of Variation 29.4 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Last Quantifiable Concentration (Clast) of M2 Metabolite | 1.682 ng/mL | Geometric Coefficient of Variation 82.8 |
Secondary
Last Quantifiable Concentration (Clast) of M3 Metabolite
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Last Quantifiable Concentration (Clast) of M3 Metabolite | 2.211 ng/mL | Geometric Coefficient of Variation 46.2 |
| Balovaptan 20 mg Fasted | Last Quantifiable Concentration (Clast) of M3 Metabolite | 2.279 ng/mL | Geometric Coefficient of Variation 55.4 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Last Quantifiable Concentration (Clast) of M3 Metabolite | 2.837 ng/mL | Geometric Coefficient of Variation 82.1 |
Secondary
Maximum Plasma Concentration (Cmax) of Esomeprazole
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Maximum Plasma Concentration (Cmax) of Esomeprazole | 1255.2 ng/mL | Geometric Coefficient of Variation 36.9 |
Secondary
Maximum Plasma Concentration (Cmax) of M2 Metabolite
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Maximum Plasma Concentration (Cmax) of M2 Metabolite | 11.27 ng/mL | Geometric Coefficient of Variation 27 |
| Balovaptan 20 mg Fasted | Maximum Plasma Concentration (Cmax) of M2 Metabolite | 11.44 ng/mL | Geometric Coefficient of Variation 30.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Maximum Plasma Concentration (Cmax) of M2 Metabolite | 11.68 ng/mL | Geometric Coefficient of Variation 30.1 |
Secondary
Maximum Plasma Concentration (Cmax) of M3 Metabolite
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Maximum Plasma Concentration (Cmax) of M3 Metabolite | 15.96 ng/mL | Geometric Coefficient of Variation 37 |
| Balovaptan 20 mg Fasted | Maximum Plasma Concentration (Cmax) of M3 Metabolite | 16.91 ng/mL | Geometric Coefficient of Variation 40.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Maximum Plasma Concentration (Cmax) of M3 Metabolite | 16.85 ng/mL | Geometric Coefficient of Variation 32.3 |
Secondary
Percentage of Patricipants With Adverse Events (AEs)
Time frame: Randomization to end of study (up to approximately 7 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Balovaptan 20 mg Fed | Percentage of Patricipants With Adverse Events (AEs) | 1 Participants |
| Balovaptan 20 mg Fasted | Percentage of Patricipants With Adverse Events (AEs) | 1 Participants |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Percentage of Patricipants With Adverse Events (AEs) | 1 Participants |
Secondary
Plasma Concentrations of Esomeprazole
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
Population: Number of analyzed participants reflects number of participants whose samples were available at given timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Balovaptan 20 mg Fed | Plasma Concentrations of Esomeprazole | Predose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of Esomeprazole | 0.25 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of Esomeprazole | 0.5 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of Esomeprazole | 1 Hrs Postdose | 171.8 ng/mL | Geometric Coefficient of Variation 171.5 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Esomeprazole | 1.5 Hrs Postdose | 242.6 ng/mL | Geometric Coefficient of Variation 102.8 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Esomeprazole | 2 Hrs Postdose | 697.1 ng/mL | Geometric Coefficient of Variation 66.2 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Esomeprazole | 3 Hrs Postdose | 984.4 ng/mL | Geometric Coefficient of Variation 36.1 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Esomeprazole | 4 Hrs Postdose | 770.7 ng/mL | Geometric Coefficient of Variation 34.7 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Esomeprazole | 6 Hrs Postdose | 336.6 ng/mL | Geometric Coefficient of Variation 59.8 |
| Balovaptan 20 mg Fed | Plasma Concentrations of Esomeprazole | 8 Hrs Postdose | 133.3 ng/mL | Geometric Coefficient of Variation 78.8 |
Secondary
Plasma Concentrations of M2 Analyte
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
Population: Number of analyzed participants reflects number of participants whose samples were available at given timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 12 Hrs Postdose | 6.921 ng/mL | Geometric Coefficient of Variation 40.4 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 2.5 Hrs Postdose | 2.236 ng/mL | Geometric Coefficient of Variation 83.3 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 36 Hrs Postdose | 10.509 ng/mL | Geometric Coefficient of Variation 29.6 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 8 Hrs Postdose | 5.223 ng/mL | Geometric Coefficient of Variation 48.9 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 3 Hrs Postdose | 2.714 ng/mL | Geometric Coefficient of Variation 80 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 72 Hrs Postdose | 6.576 ng/mL | Geometric Coefficient of Variation 30.7 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 6 Hrs Postdose | 4.158 ng/mL | Geometric Coefficient of Variation 50.9 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 3.5 Hrs Postdose | 2.780 ng/mL | Geometric Coefficient of Variation 75.7 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 0.5 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 5 Hrs Postdose | 3.756 ng/mL | Geometric Coefficient of Variation 60.5 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 4 Hrs Postdose | 3.208 ng/mL | Geometric Coefficient of Variation 65.5 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | Predose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 192 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 48 Hrs Postdose | 9.383 ng/mL | Geometric Coefficient of Variation 28.2 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 1 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 144 Hrs Postdose | 2.033 ng/mL | Geometric Coefficient of Variation 64.7 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 24 Hrs Postdose | 10.123 ng/mL | Geometric Coefficient of Variation 29.4 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 1.5 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 96 Hrs Postdose | 4.050 ng/mL | Geometric Coefficient of Variation 41.6 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 16 Hrs Postdose | 8.384 ng/mL | Geometric Coefficient of Variation 39.7 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 2 Hrs Postdose | 2.021 ng/mL | Geometric Coefficient of Variation 97.7 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M2 Analyte | 0.25 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 4 Hrs Postdose | 4.860 ng/mL | Geometric Coefficient of Variation 49.1 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | Predose | NA ng/mL | — |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 24 Hrs Postdose | 10.928 ng/mL | Geometric Coefficient of Variation 30.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 36 Hrs Postdose | 10.519 ng/mL | Geometric Coefficient of Variation 27.4 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 0.25 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 0.5 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 1 Hrs Postdose | 3.081 ng/mL | Geometric Coefficient of Variation 62.2 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 1.5 Hrs Postdose | 3.421 ng/mL | Geometric Coefficient of Variation 57.2 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 2 Hrs Postdose | 3.637 ng/mL | Geometric Coefficient of Variation 45.6 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 2.5 Hrs Postdose | 3.724 ng/mL | Geometric Coefficient of Variation 48.8 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 3 Hrs Postdose | 4.293 ng/mL | Geometric Coefficient of Variation 49.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 3.5 Hrs Postdose | 4.724 ng/mL | Geometric Coefficient of Variation 49.2 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 5 Hrs Postdose | 5.696 ng/mL | Geometric Coefficient of Variation 47.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 6 Hrs Postdose | 5.797 ng/mL | Geometric Coefficient of Variation 50 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 8 Hrs Postdose | 6.550 ng/mL | Geometric Coefficient of Variation 46.6 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 12 Hrs Postdose | 7.889 ng/mL | Geometric Coefficient of Variation 39.5 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 16 Hrs Postdose | 9.207 ng/mL | Geometric Coefficient of Variation 40.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 48 Hrs Postdose | 9.134 ng/mL | Geometric Coefficient of Variation 25.8 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 72 Hrs Postdose | 5.998 ng/mL | Geometric Coefficient of Variation 27.5 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 96 Hrs Postdose | 3.748 ng/mL | Geometric Coefficient of Variation 32.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 144 Hrs Postdose | 2.139 ng/mL | Geometric Coefficient of Variation 71.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M2 Analyte | 192 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 2 Hrs Postdose | 3.019 ng/mL | Geometric Coefficient of Variation 54.9 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 96 Hrs Postdose | 4.450 ng/mL | Geometric Coefficient of Variation 27.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 12 Hrs Postdose | 8.426 ng/mL | Geometric Coefficient of Variation 42.9 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 1.5 Hrs Postdose | 2.690 ng/mL | Geometric Coefficient of Variation 72.6 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 36 Hrs Postdose | 11.409 ng/mL | Geometric Coefficient of Variation 26.9 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 16 Hrs Postdose | 9.563 ng/mL | Geometric Coefficient of Variation 34.2 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 1 Hrs Postdose | 2.649 ng/mL | Geometric Coefficient of Variation 95.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 0.5 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 192 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 48 Hrs Postdose | 10.191 ng/mL | Geometric Coefficient of Variation 26.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 0.25 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 144 Hrs Postdose | 2.107 ng/mL | Geometric Coefficient of Variation 45.2 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 4 Hrs Postdose | 4.749 ng/mL | Geometric Coefficient of Variation 41.1 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 3.5 Hrs Postdose | 4.217 ng/mL | Geometric Coefficient of Variation 44.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 72 Hrs Postdose | 27.5 ng/mL | Geometric Coefficient of Variation 23.5 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 5 Hrs Postdose | 5.471 ng/mL | Geometric Coefficient of Variation 44.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 3 Hrs Postdose | 3.878 ng/mL | Geometric Coefficient of Variation 43.2 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | Predose | NA ng/mL | — |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 6 Hrs Postdose | 5.775 ng/mL | Geometric Coefficient of Variation 39.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 2.5 Hrs Postdose | 3.502 ng/mL | Geometric Coefficient of Variation 46.4 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 24 Hrs Postdose | 10.887 ng/mL | Geometric Coefficient of Variation 33 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M2 Analyte | 8 Hrs Postdose | 6.512 ng/mL | Geometric Coefficient of Variation 40.8 |
Secondary
Plasma Concentrations of M3 Analyte
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
Population: Number of analyzed participants reflects number of participants whose samples were available at given timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 0.5 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 16 Hrs Postdose | 14.113 ng/mL | Geometric Coefficient of Variation 40.9 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 3 Hrs Postdose | 6.616 ng/mL | Geometric Coefficient of Variation 85.9 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 0.25 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 3.5 Hrs Postdose | 5.985 ng/mL | Geometric Coefficient of Variation 78 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 12 Hrs Postdose | 12.697 ng/mL | Geometric Coefficient of Variation 5.7063 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 4 Hrs Postdose | 6.408 ng/mL | Geometric Coefficient of Variation 71.4 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 96 Hrs Postdose | 6.066 ng/mL | Geometric Coefficient of Variation 31.6 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 8 Hrs Postdose | 11.157 ng/mL | Geometric Coefficient of Variation 47.8 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 5 Hrs Postdose | 8.901 ng/mL | Geometric Coefficient of Variation 58.8 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 72 Hrs Postdose | 8.108 ng/mL | Geometric Coefficient of Variation 28.3 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 6 Hrs Postdose | 9.691 ng/mL | Geometric Coefficient of Variation 59.8 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 1 Hrs Postdose | 2.347 ng/mL | Geometric Coefficient of Variation 138.4 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 192 Hrs Postdose | 2.211 ng/mL | Geometric Coefficient of Variation 46.2 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 48 Hrs Postdose | 11.665 ng/mL | Geometric Coefficient of Variation 26.4 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 1.5 Hrs Postdose | 3.787 ng/mL | Geometric Coefficient of Variation 95.1 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 144 Hrs Postdose | 3.525 ng/mL | Geometric Coefficient of Variation 45.5 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 36 Hrs Postdose | 13.626 ng/mL | Geometric Coefficient of Variation 26.4 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 2 Hrs Postdose | 5.211 ng/mL | Geometric Coefficient of Variation 83 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | Predose | NA ng/mL | — |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 24 Hrs Postdose | 14.388 ng/mL | Geometric Coefficient of Variation 33.4 |
| Balovaptan 20 mg Fed | Plasma Concentrations of M3 Analyte | 2.5 Hrs Postdose | 5.520 ng/mL | Geometric Coefficient of Variation 83.5 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 192 Hrs Postdose | 2.279 ng/mL | Geometric Coefficient of Variation 55.4 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 0.5 Hrs Postdose | 5.006 ng/mL | Geometric Coefficient of Variation 118 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | Predose | NA ng/mL | — |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 0.25 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 1 Hrs Postdose | 7.812 ng/mL | Geometric Coefficient of Variation 60.6 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 1.5 Hrs Postdose | 8.928 ng/mL | Geometric Coefficient of Variation 59.6 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 2 Hrs Postdose | 10.157 ng/mL | Geometric Coefficient of Variation 46.8 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 2.5 Hrs Postdose | 10.539 ng/mL | Geometric Coefficient of Variation 47.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 3 Hrs Postdose | 10.980 ng/mL | Geometric Coefficient of Variation 48.6 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 3.5 Hrs Postdose | 11.369 ng/mL | Geometric Coefficient of Variation 50.8 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 4 Hrs Postdose | 12.160 ng/mL | Geometric Coefficient of Variation 50.8 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 5 Hrs Postdose | 13.241 ng/mL | Geometric Coefficient of Variation 41.5 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 6 Hrs Postdose | 12.831 ng/mL | Geometric Coefficient of Variation 47.9 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 8 Hrs Postdose | 13.875 ng/mL | Geometric Coefficient of Variation 48.4 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 12 Hrs Postdose | 14.296 ng/mL | Geometric Coefficient of Variation 39.7 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 16 Hrs Postdose | 15.145 ng/mL | Geometric Coefficient of Variation 41.6 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 24 Hrs Postdose | 15.061 ng/mL | Geometric Coefficient of Variation 39.7 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 36 Hrs Postdose | 14.148 ng/mL | Geometric Coefficient of Variation 29.7 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 48 Hrs Postdose | 11.470 ng/mL | Geometric Coefficient of Variation 29 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 72 Hrs Postdose | 8.129 ng/mL | Geometric Coefficient of Variation 31.3 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 96 Hrs Postdose | 6.111 ng/mL | Geometric Coefficient of Variation 42.4 |
| Balovaptan 20 mg Fasted | Plasma Concentrations of M3 Analyte | 144 Hrs Postdose | 3.747 ng/mL | Geometric Coefficient of Variation 45.7 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 192 Hrs Postdose | 2.569 ng/mL | Geometric Coefficient of Variation 54.2 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 16 Hrs Postdose | 15.049 ng/mL | Geometric Coefficient of Variation 30.1 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 2 Hrs Postdose | 8.859 ng/mL | Geometric Coefficient of Variation 55.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 96 Hrs Postdose | 6.653 ng/mL | Geometric Coefficient of Variation 34.1 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 24 Hrs Postdose | 16.092 ng/mL | Geometric Coefficient of Variation 29.9 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 1.5 Hrs Postdose | 6.705 ng/mL | Geometric Coefficient of Variation 62.6 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | Predose | NA ng/mL | — |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 36 Hrs Postdose | 13.793 ng/mL | Geometric Coefficient of Variation 27.7 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 1 Hrs Postdose | 5.556 ng/mL | Geometric Coefficient of Variation 78.9 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 3 Hrs Postdose | 10.887 ng/mL | Geometric Coefficient of Variation 39.4 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 48 Hrs Postdose | 12.966 ng/mL | Geometric Coefficient of Variation 27.3 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 0.5 Hrs Postdose | 3.172 ng/mL | Geometric Coefficient of Variation 127.1 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 5 Hrs Postdose | 12.998 ng/mL | Geometric Coefficient of Variation 46.7 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 144 Hrs Postdose | 3.957 ng/mL | Geometric Coefficient of Variation 45.2 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 6 Hrs Postdose | 13.442 ng/mL | Geometric Coefficient of Variation 39.6 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 4 Hrs Postdose | 11.969 ng/mL | Geometric Coefficient of Variation 38 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 72 Hrs Postdose | 9.023 ng/mL | Geometric Coefficient of Variation 25.2 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 8 Hrs Postdose | 13.762 ng/mL | Geometric Coefficient of Variation 40.4 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 3.5 Hrs Postdose | 11.316 ng/mL | Geometric Coefficient of Variation 41.2 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 0.25 Hrs Postdose | NA ng/mL | — |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 12 Hrs Postdose | 14.287 ng/mL | Geometric Coefficient of Variation 36.3 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Plasma Concentrations of M3 Analyte | 2.5 Hrs Postdose | 9.853 ng/mL | Geometric Coefficient of Variation 45.8 |
Secondary
Terminal Elimination Phase Half-Life (T1/2) of Esomeprazole
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Terminal Elimination Phase Half-Life (T1/2) of Esomeprazole | 1.590 h | Geometric Coefficient of Variation 29.2 |
Secondary
Terminal Elimination Phase Half-Life (T1/2) of M2 Metabolite
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Terminal Elimination Phase Half-Life (T1/2) of M2 Metabolite | 38.99 h | Geometric Coefficient of Variation 29.2 |
| Balovaptan 20 mg Fasted | Terminal Elimination Phase Half-Life (T1/2) of M2 Metabolite | 37.81 h | Geometric Coefficient of Variation 30.7 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Terminal Elimination Phase Half-Life (T1/2) of M2 Metabolite | 39.19 h | Geometric Coefficient of Variation 22.7 |
Secondary
Terminal Elimination Phase Half-Life (T1/2) of M3 Metabolite
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Terminal Elimination Phase Half-Life (T1/2) of M3 Metabolite | 57.40 h | Geometric Coefficient of Variation 17.3 |
| Balovaptan 20 mg Fasted | Terminal Elimination Phase Half-Life (T1/2) of M3 Metabolite | 59.30 h | Geometric Coefficient of Variation 17.6 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Terminal Elimination Phase Half-Life (T1/2) of M3 Metabolite | 57.81 h | Geometric Coefficient of Variation 19.2 |
Secondary
Terminal Phase Rate Constant (λz) of Esomeprazole
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
Population: For two participants there was no terminal phase, so they are excluded form the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Terminal Phase Rate Constant (λz) of Esomeprazole | 0.4197 /h | Geometric Coefficient of Variation 30.1 |
Secondary
Terminal Phase Rate Constant (λz) of M2 Metabolite
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
Population: For one participant there was no terminal phase, so they are excluded form the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Terminal Phase Rate Constant (λz) of M2 Metabolite | 0.0178 /h | Geometric Coefficient of Variation 30.3 |
| Balovaptan 20 mg Fasted | Terminal Phase Rate Constant (λz) of M2 Metabolite | 0.0174 /h | Geometric Coefficient of Variation 31.9 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Terminal Phase Rate Constant (λz) of M2 Metabolite | 0.0171 /h | Geometric Coefficient of Variation 25.5 |
Secondary
Terminal Phase Rate Constant (λz) of M3 Metabolite
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
Population: For one participant there was no terminal phase, so they are excluded form the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Terminal Phase Rate Constant (λz) of M3 Metabolite | 0.0112 /h | Geometric Coefficient of Variation 22.1 |
| Balovaptan 20 mg Fasted | Terminal Phase Rate Constant (λz) of M3 Metabolite | 0.0107 /h | Geometric Coefficient of Variation 24.8 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Terminal Phase Rate Constant (λz) of M3 Metabolite | 0.0107 /h | Geometric Coefficient of Variation 25.2 |
Secondary
Time to Reach Cmax in Plasma (Tmax) of Esomeprazole
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Balovaptan 20 mg Fed | Time to Reach Cmax in Plasma (Tmax) of Esomeprazole | 2.00 h |
Secondary
Time to Reach Cmax in Plasma (Tmax) of M2 Metabolite
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Balovaptan 20 mg Fed | Time to Reach Cmax in Plasma (Tmax) of M2 Metabolite | 36.00 h |
| Balovaptan 20 mg Fasted | Time to Reach Cmax in Plasma (Tmax) of M2 Metabolite | 24.03 h |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Time to Reach Cmax in Plasma (Tmax) of M2 Metabolite | 36.00 h |
Secondary
Time to Reach Cmax in Plasma (Tmax) of M3 Metabolite
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Balovaptan 20 mg Fed | Time to Reach Cmax in Plasma (Tmax) of M3 Metabolite | 20.01 h |
| Balovaptan 20 mg Fasted | Time to Reach Cmax in Plasma (Tmax) of M3 Metabolite | 24.02 h |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Time to Reach Cmax in Plasma (Tmax) of M3 Metabolite | 16.00 h |
Secondary
Time To the Last Quantifiable Concentration (Tlast) of Esomeprazole
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Time To the Last Quantifiable Concentration (Tlast) of Esomeprazole | 8.002 h | Geometric Coefficient of Variation 0.1 |
Secondary
Time To the Last Quantifiable Concentration (Tlast) of M2 Metabolite
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Time To the Last Quantifiable Concentration (Tlast) of M2 Metabolite | 155.3 h | Geometric Coefficient of Variation 21.2 |
| Balovaptan 20 mg Fasted | Time To the Last Quantifiable Concentration (Tlast) of M2 Metabolite | 142.4 h | Geometric Coefficient of Variation 25.2 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Time To the Last Quantifiable Concentration (Tlast) of M2 Metabolite | 142.4 h | Geometric Coefficient of Variation 29.5 |
Secondary
Time To the Last Quantifiable Concentration (Tlast) of M3 Metabolite
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Balovaptan 20 mg Fed | Time To the Last Quantifiable Concentration (Tlast) of M3 Metabolite | 192.0 h | Geometric Coefficient of Variation 0 |
| Balovaptan 20 mg Fasted | Time To the Last Quantifiable Concentration (Tlast) of M3 Metabolite | 192.0 h | Geometric Coefficient of Variation 0 |
| Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted | Time To the Last Quantifiable Concentration (Tlast) of M3 Metabolite | 168.7 h | Geometric Coefficient of Variation 23.1 |