Healthy Volunteers
Conditions
Brief summary
This study was a non-randomized, open-label, parallel group, two-treatment study in healthy volunteers to investigate the absolute oral bioavailability of balovaptan. The study was conducted at 1 site in the Netherlands.
Interventions
DRUGOral Balovaptan
In Period 1, balovaptan was administered as a single oral dose. In Period 2, balovaptan was administered as an oral dose once daily on Day 1 to Day 14.
DRUGIV Balovaptan
In Period 1, IV infusion of balovaptan was administered after the balovaptan oral dose. In Period 2, IV infusion of balovaptan was administered after the final oral dose of balovaptan.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female subjects. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, urinalysis, and serology. * Body Mass Index of 18 to 30 kg/m2, inclusive. * For women of childbearing potential: agreement to use at least 2 acceptable contraceptive methods during the treatment period and for 90 days after the last dose of study drug. * For men: agreement to use contraceptive measures, and agreement to refrain from donating sperm until 90 days after the last dose of study drug.
Exclusion criteria
* Female subjects who are pregnant or lactating. * Any condition or disease detected during the medical interview/physical examination that would render the subject unsuitable for the study, place the subject at undue risk or interfere with the ability of the subject to complete the study in the opinion of the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Bioavailability of Oral Balovaptan at Dose Level A (Cohort 1) | Day 1 of Period 1 (Period 1 is 14 days). | Absolute oral bioavailability of a single dose A of balovaptan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clast of M2 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Clast of M3 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Absolute Bioavailability of Oral Balovaptan at Dose Level B (Cohort 2) | Day 1 of Period 1 (Period 1 is 14 days). | Absolute oral bioavailability of a single dose B balovaptan. |
| Absolute Bioavailability of Oral Balovaptan at Dose A and Dose B | Day 14 of Period 2 (Period 2 is 19 days). | Absolute oral bioavailability of balovaptan after once daily doses of Dose A and Dose B for 14 days. |
| Maximum Plasma Concentration (Cmax) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Cmax of Oral Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Cmax of M2 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Cmax of M3 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Time to Maximum Observed Plasma Concentration (Tmax) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Tmax of Oral Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Tmax of M2 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Tmax of M3 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Apparent Terminal Half-Life (t1/2) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| T1/2 of Oral Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| T1/2 of M2 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| T1/2 of M3 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Plasma Concentration Time Point (AUC0-last) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days) | — |
| AUC0-last of Oral Balovaptan | Day 1 of Period 1 (Period 1 is 14 days) | — |
| AUC0-last of M2 Metabolites | Day 1 of Period 1 (Period 1 is 14 days) | — |
| AUC0-last of M3 Metabolites | Day 1 of Period 1 (Period 1 is 14 days) | — |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| AUC0-inf of Oral Balovaptan | Day 1 of Period 1 (Period 1 is 14 days). | — |
| AUC0-inf of M2 Metabolites | Day 1 of Period 1 (Period 1 is 14 days). | — |
| AUC0-inf of M3 Metabolites | Day 1 of Period 1 (Period 1 is 14 days). | — |
| Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUC0-24) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| AUC0-24 of Oral Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| AUC0-24 of M2 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| AUC0-24 of M3 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Last Measurable Plasma Concentration (Clast) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Time of Last Measurable Plasma Concentration (Tlast) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Tlast of Oral Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Tlast of M2 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Tlast of M3 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Terminal Elimination Rate Constant (λz) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| λz of Oral Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Clast of Oral Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| λz of M3 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Total Body Clearance (CL) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Volume of Distribution (Vss) of IV Balovaptan | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
| Percentage of Participants With Treatment-Emergent Adverse Events | Up to 35 days from screening (sceening is up to 28 days prior to admission to the clinical research unit). | — |
| λz of M2 Metabolites | Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). | — |
Countries
Netherlands
Participant flow
Recruitment details
The study was conducted at 1 site in the Netherlands.
Pre-assignment details
Participants in this study included healthy volunteers.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Participants received the study drug at dose level A in 2 periods. There was a minimum of a 14-day wash out period between Day 1 of Period 1 and Day 1 of Period 2. | 8 |
| Cohort 2 Participants received the study drug at dose level B in 2 periods. There was a minimum of a 14-day wash out period between Day 1 of Period 1 and Day 1 of Period 2. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Cohort 2 | Total | Cohort 1 |
|---|---|---|---|
| Age, Continuous | 33.5 Years STANDARD_DEVIATION 13.24 | 37.4 Years STANDARD_DEVIATION 14.85 | 41.4 Years STANDARD_DEVIATION 16.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 14 Participants | 8 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 14 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 12 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 4 / 8 | 6 / 8 | 5 / 8 | 7 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Absolute Bioavailability of Oral Balovaptan at Dose Level A (Cohort 1)
Absolute oral bioavailability of a single dose A of balovaptan.
Time frame: Day 1 of Period 1 (Period 1 is 14 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Absolute Bioavailability of Oral Balovaptan at Dose Level A (Cohort 1) | 100.6 Percentage | Geometric Coefficient of Variation 31.4 |
Secondary
Absolute Bioavailability of Oral Balovaptan at Dose A and Dose B
Absolute oral bioavailability of balovaptan after once daily doses of Dose A and Dose B for 14 days.
Time frame: Day 14 of Period 2 (Period 2 is 19 days).
Population: PK analysis consisted of all receiving at least 1 dose balovaptan.Participants excluded from analysis, if significantly violated inclusion/exclusion criteria, deviated significantly from protocol, or if data unavailable/incomplete.There were 2 outliers;sensitivity analysis excluding those 2,resulted in similar bioavailability across all treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Absolute Bioavailability of Oral Balovaptan at Dose A and Dose B | 82.3 Percentage | Geometric Coefficient of Variation 72.4 |
| Cohort 2 | Absolute Bioavailability of Oral Balovaptan at Dose A and Dose B | 103.1 Percentage | Geometric Coefficient of Variation 4.1 |
Secondary
Absolute Bioavailability of Oral Balovaptan at Dose Level B (Cohort 2)
Absolute oral bioavailability of a single dose B balovaptan.
Time frame: Day 1 of Period 1 (Period 1 is 14 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Absolute Bioavailability of Oral Balovaptan at Dose Level B (Cohort 2) | 108.2 Percentage | Geometric Coefficient of Variation 5.9 |
Secondary
Apparent Terminal Half-Life (t1/2) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Apparent Terminal Half-Life (t1/2) of IV Balovaptan | Day 1 of Period 1 | 35.2 Hour | Geometric Coefficient of Variation 23.7 |
| Cohort 1 | Apparent Terminal Half-Life (t1/2) of IV Balovaptan | Day 14 of Period 2 | 27.7 Hour | Geometric Coefficient of Variation 18.3 |
| Cohort 2 | Apparent Terminal Half-Life (t1/2) of IV Balovaptan | Day 1 of Period 1 | 19.5 Hour | Geometric Coefficient of Variation 34 |
| Cohort 2 | Apparent Terminal Half-Life (t1/2) of IV Balovaptan | Day 14 of Period 2 | 15.7 Hour | Geometric Coefficient of Variation 28.2 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of IV Balovaptan | Day 1 of Period 1 | 8929 h*pg/mL | Geometric Coefficient of Variation 34 |
| Cohort 1 | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of IV Balovaptan | Day 14 of Period 2 | 15492 h*pg/mL | Geometric Coefficient of Variation 71.5 |
| Cohort 2 | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of IV Balovaptan | Day 1 of Period 1 | 9569 h*pg/mL | Geometric Coefficient of Variation 19.8 |
| Cohort 2 | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of IV Balovaptan | Day 14 of Period 2 | 10430 h*pg/mL | Geometric Coefficient of Variation 27.9 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Plasma Concentration Time Point (AUC0-last) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days)
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Plasma Concentration Time Point (AUC0-last) of IV Balovaptan | 8087 h*pg/mL | Geometric Coefficient of Variation 35.5 |
| Cohort 2 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Plasma Concentration Time Point (AUC0-last) of IV Balovaptan | 9372 h*pg/mL | Geometric Coefficient of Variation 19.3 |
Secondary
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUC0-24) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUC0-24) of IV Balovaptan | Day 1 of Period 1 | 4400 h*pg/mL | Geometric Coefficient of Variation 42.8 |
| Cohort 1 | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUC0-24) of IV Balovaptan | Day 14 of Period 2 | 9898 h*pg/mL | Geometric Coefficient of Variation 89 |
| Cohort 2 | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUC0-24) of IV Balovaptan | Day 1 of Period 1 | 6690 h*pg/mL | Geometric Coefficient of Variation 13.9 |
| Cohort 2 | Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUC0-24) of IV Balovaptan | Day 14 of Period 2 | 7908 h*pg/mL | Geometric Coefficient of Variation 19.4 |
Secondary
AUC0-24 of M2 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | AUC0-24 of M2 Metabolites | Day 1 of Period 1 | 54.7 h*ng/mL | Geometric Coefficient of Variation 73.5 |
| Cohort 1 | AUC0-24 of M2 Metabolites | Day 14 of Period 2 | 404 h*ng/mL | Geometric Coefficient of Variation 64.2 |
| Cohort 2 | AUC0-24 of M2 Metabolites | Day 1 of Period 1 | 427 h*ng/mL | Geometric Coefficient of Variation 41.1 |
| Cohort 2 | AUC0-24 of M2 Metabolites | Day 14 of Period 2 | 2087 h*ng/mL | Geometric Coefficient of Variation 32.1 |
Secondary
AUC0-24 of M3 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | AUC0-24 of M3 Metabolites | Day 1 of Period 1 | 106 h*ng/mL | Geometric Coefficient of Variation 40.5 |
| Cohort 1 | AUC0-24 of M3 Metabolites | Day 14 of Period 2 | 1102 h*ng/mL | Geometric Coefficient of Variation 17.4 |
| Cohort 2 | AUC0-24 of M3 Metabolites | Day 1 of Period 1 | 1188 h*ng/mL | Geometric Coefficient of Variation 29.2 |
| Cohort 2 | AUC0-24 of M3 Metabolites | Day 14 of Period 2 | 4727 h*ng/mL | Geometric Coefficient of Variation 28.3 |
Secondary
AUC0-24 of Oral Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | AUC0-24 of Oral Balovaptan | Day 1 of Period 1 | 458 h*ng/mL | Geometric Coefficient of Variation 22.3 |
| Cohort 1 | AUC0-24 of Oral Balovaptan | Day 14 of Period 2 | 1322 h*ng/mL | Geometric Coefficient of Variation 19.3 |
| Cohort 2 | AUC0-24 of Oral Balovaptan | Day 1 of Period 1 | 3632 h*ng/mL | Geometric Coefficient of Variation 15.6 |
| Cohort 2 | AUC0-24 of Oral Balovaptan | Day 14 of Period 2 | 5505 h*ng/mL | Geometric Coefficient of Variation 30.7 |
Secondary
AUC0-inf of M2 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | AUC0-inf of M2 Metabolites | 520 h*ng/mL | Geometric Coefficient of Variation 55.1 |
| Cohort 2 | AUC0-inf of M2 Metabolites | 1819 h*ng/mL | Geometric Coefficient of Variation 36.5 |
Secondary
AUC0-inf of M3 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | AUC0-inf of M3 Metabolites | 1122 h*ng/mL | Geometric Coefficient of Variation 14.8 |
| Cohort 2 | AUC0-inf of M3 Metabolites | 4221 h*ng/mL | Geometric Coefficient of Variation 27.5 |
Secondary
AUC0-inf of Oral Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | AUC0-inf of Oral Balovaptan | 1008 h*ng/mL | Geometric Coefficient of Variation 24.4 |
| Cohort 2 | AUC0-inf of Oral Balovaptan | 5550 h*ng/mL | Geometric Coefficient of Variation 23.9 |
Secondary
AUC0-last of M2 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days)
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | AUC0-last of M2 Metabolites | 297 h*ng/mL | Geometric Coefficient of Variation 72 |
| Cohort 2 | AUC0-last of M2 Metabolites | 1751 h*ng/mL | Geometric Coefficient of Variation 37.5 |
Secondary
AUC0-last of M3 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days)
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | AUC0-last of M3 Metabolites | 754 h*ng/mL | Geometric Coefficient of Variation 24.3 |
| Cohort 2 | AUC0-last of M3 Metabolites | 3908 h*ng/mL | Geometric Coefficient of Variation 24.5 |
Secondary
AUC0-last of Oral Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days)
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | AUC0-last of Oral Balovaptan | 937 h*ng/mL | Geometric Coefficient of Variation 25.6 |
| Cohort 2 | AUC0-last of Oral Balovaptan | 5497 h*ng/mL | Geometric Coefficient of Variation 23.9 |
Secondary
Clast of M2 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Clast of M2 Metabolites | Day 1 of Period 1 | 1.24 ng/mL | Geometric Coefficient of Variation 10.4 |
| Cohort 1 | Clast of M2 Metabolites | Day 14 of Period 2 | 3.19 ng/mL | Geometric Coefficient of Variation 51.2 |
| Cohort 2 | Clast of M2 Metabolites | Day 1 of Period 1 | 1.25 ng/mL | Geometric Coefficient of Variation 15.6 |
| Cohort 2 | Clast of M2 Metabolites | Day 14 of Period 2 | 9.95 ng/mL | Geometric Coefficient of Variation 58 |
Secondary
Clast of M3 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Clast of M3 Metabolites | Day 1 of Period 1 | 1.43 ng/mL | Geometric Coefficient of Variation 24.4 |
| Cohort 1 | Clast of M3 Metabolites | Day 14 of Period 2 | 11.9 ng/mL | Geometric Coefficient of Variation 21.3 |
| Cohort 2 | Clast of M3 Metabolites | Day 1 of Period 1 | 2.74 ng/mL | Geometric Coefficient of Variation 55.8 |
| Cohort 2 | Clast of M3 Metabolites | Day 14 of Period 2 | 17.6 ng/mL | Geometric Coefficient of Variation 64 |
Secondary
Clast of Oral Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Clast of Oral Balovaptan | Day 1 of Period 1 | 1.22 ng/mL | Geometric Coefficient of Variation 13.4 |
| Cohort 1 | Clast of Oral Balovaptan | Day 14 of Period 2 | 3.51 ng/mL | Geometric Coefficient of Variation 62.2 |
| Cohort 2 | Clast of Oral Balovaptan | Day 1 of Period 1 | 1.22 ng/mL | Geometric Coefficient of Variation 10.6 |
| Cohort 2 | Clast of Oral Balovaptan | Day 14 of Period 2 | 3.40 ng/mL | Geometric Coefficient of Variation 88.6 |
Secondary
Cmax of M2 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Cmax of M2 Metabolites | Day 1 of Period 1 | 3.87 ng/mL | Geometric Coefficient of Variation 62.1 |
| Cohort 1 | Cmax of M2 Metabolites | Day 14 of Period 2 | 20.3 ng/mL | Geometric Coefficient of Variation 65.8 |
| Cohort 2 | Cmax of M2 Metabolites | Day 1 of Period 1 | 23.6 ng/mL | Geometric Coefficient of Variation 38.1 |
| Cohort 2 | Cmax of M2 Metabolites | Day 14 of Period 2 | 105 ng/mL | Geometric Coefficient of Variation 29 |
Secondary
Cmax of M3 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Cmax of M3 Metabolites | Day 1 of Period 1 | 6.18 ng/mL | Geometric Coefficient of Variation 28.6 |
| Cohort 1 | Cmax of M3 Metabolites | Day 14 of Period 2 | 57.2 ng/mL | Geometric Coefficient of Variation 18.8 |
| Cohort 2 | Cmax of M3 Metabolites | Day 1 of Period 1 | 57.9 ng/mL | Geometric Coefficient of Variation 30.3 |
| Cohort 2 | Cmax of M3 Metabolites | Day 14 of Period 2 | 260 ng/mL | Geometric Coefficient of Variation 26.5 |
Secondary
Cmax of Oral Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Cmax of Oral Balovaptan | Day 1 of Period 1 | 36.9 ng/mL | Geometric Coefficient of Variation 36.8 |
| Cohort 1 | Cmax of Oral Balovaptan | Day 14 of Period 2 | 108 ng/mL | Geometric Coefficient of Variation 20.4 |
| Cohort 2 | Cmax of Oral Balovaptan | Day 1 of Period 1 | 443 ng/mL | Geometric Coefficient of Variation 15.2 |
| Cohort 2 | Cmax of Oral Balovaptan | Day 14 of Period 2 | 643 ng/mL | Geometric Coefficient of Variation 25 |
Secondary
Last Measurable Plasma Concentration (Clast) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Last Measurable Plasma Concentration (Clast) of IV Balovaptan | Day 1 of Period 1 | 13.6 pg/mL | Geometric Coefficient of Variation 49.7 |
| Cohort 1 | Last Measurable Plasma Concentration (Clast) of IV Balovaptan | Day 14 of Period 2 | 12.5 pg/mL | Geometric Coefficient of Variation 45.5 |
| Cohort 2 | Last Measurable Plasma Concentration (Clast) of IV Balovaptan | Day 1 of Period 1 | 6.62 pg/mL | Geometric Coefficient of Variation 29.8 |
| Cohort 2 | Last Measurable Plasma Concentration (Clast) of IV Balovaptan | Day 14 of Period 2 | 6.92 pg/mL | Geometric Coefficient of Variation 22.6 |
Secondary
Maximum Plasma Concentration (Cmax) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Maximum Plasma Concentration (Cmax) of IV Balovaptan | Day 1 of Period 1 | 688 pg/mL | Geometric Coefficient of Variation 30.5 |
| Cohort 1 | Maximum Plasma Concentration (Cmax) of IV Balovaptan | Day 14 of Period 2 | 1591 pg/mL | Geometric Coefficient of Variation 115.8 |
| Cohort 2 | Maximum Plasma Concentration (Cmax) of IV Balovaptan | Day 1 of Period 1 | 1601 pg/mL | Geometric Coefficient of Variation 28.2 |
| Cohort 2 | Maximum Plasma Concentration (Cmax) of IV Balovaptan | Day 14 of Period 2 | 1974 pg/mL | Geometric Coefficient of Variation 37.9 |
Secondary
Percentage of Participants With Treatment-Emergent Adverse Events
Time frame: Up to 35 days from screening (sceening is up to 28 days prior to admission to the clinical research unit).
Population: The safety analysis population consisted of participants who received at least one dose of balovaptan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Percentage of Participants With Treatment-Emergent Adverse Events | 50 Percentage |
| Cohort 2 | Percentage of Participants With Treatment-Emergent Adverse Events | 75 Percentage |
| Cohort 2, Period 1 | Percentage of Participants With Treatment-Emergent Adverse Events | 63 Percentage |
| Cohort 2, Period 2 | Percentage of Participants With Treatment-Emergent Adverse Events | 88 Percentage |
Secondary
T1/2 of M2 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | T1/2 of M2 Metabolites | Day 1 of Period 1 | 48.5 Hour | Geometric Coefficient of Variation 36.7 |
| Cohort 1 | T1/2 of M2 Metabolites | Day 14 of Period 2 | 36.3 Hour | Geometric Coefficient of Variation 25 |
| Cohort 2 | T1/2 of M2 Metabolites | Day 1 of Period 1 | 35.7 Hour | Geometric Coefficient of Variation 27.2 |
| Cohort 2 | T1/2 of M2 Metabolites | Day 14 of Period 2 | 28.5 Hour | Geometric Coefficient of Variation 13.5 |
Secondary
T1/2 of M3 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | T1/2 of M3 Metabolites | Day 1 of Period 1 | 93.0 Hour | Geometric Coefficient of Variation 18.5 |
| Cohort 1 | T1/2 of M3 Metabolites | Day 14 of Period 2 | 60.3 Hour | Geometric Coefficient of Variation 29.1 |
| Cohort 2 | T1/2 of M3 Metabolites | Day 1 of Period 1 | 68.2 Hour | Geometric Coefficient of Variation 29.8 |
| Cohort 2 | T1/2 of M3 Metabolites | Day 14 of Period 2 | 33.7 Hour | Geometric Coefficient of Variation 11.2 |
Secondary
T1/2 of Oral Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | T1/2 of Oral Balovaptan | Day 1 of Period 1 | 38.8 Hour | Geometric Coefficient of Variation 25.9 |
| Cohort 1 | T1/2 of Oral Balovaptan | Day 14 of Period 2 | 31.2 Hour | Geometric Coefficient of Variation 15.6 |
| Cohort 2 | T1/2 of Oral Balovaptan | Day 1 of Period 1 | 29.1 Hour | Geometric Coefficient of Variation 28.7 |
| Cohort 2 | T1/2 of Oral Balovaptan | Day 14 of Period 2 | 22.7 Hour | Geometric Coefficient of Variation 15.7 |
Secondary
Terminal Elimination Rate Constant (λz) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Terminal Elimination Rate Constant (λz) of IV Balovaptan | Day 1 of Period 1 | 0.0197 /hour | Geometric Coefficient of Variation 23.7 |
| Cohort 1 | Terminal Elimination Rate Constant (λz) of IV Balovaptan | Day 14 of Period 2 | 0.0250 /hour | Geometric Coefficient of Variation 18.3 |
| Cohort 2 | Terminal Elimination Rate Constant (λz) of IV Balovaptan | Day 1 of Period 1 | 0.0356 /hour | Geometric Coefficient of Variation 34 |
| Cohort 2 | Terminal Elimination Rate Constant (λz) of IV Balovaptan | Day 14 of Period 2 | 0.0442 /hour | Geometric Coefficient of Variation 28.2 |
Secondary
Time of Last Measurable Plasma Concentration (Tlast) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Time of Last Measurable Plasma Concentration (Tlast) of IV Balovaptan | Day 1 of Period 1 | 106.75 Hour |
| Cohort 1 | Time of Last Measurable Plasma Concentration (Tlast) of IV Balovaptan | Day 14 of Period 2 | 106.75 Hour |
| Cohort 2 | Time of Last Measurable Plasma Concentration (Tlast) of IV Balovaptan | Day 1 of Period 1 | 100.75 Hour |
| Cohort 2 | Time of Last Measurable Plasma Concentration (Tlast) of IV Balovaptan | Day 14 of Period 2 | 82.75 Hour |
Secondary
Time to Maximum Observed Plasma Concentration (Tmax) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all partcipants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Time to Maximum Observed Plasma Concentration (Tmax) of IV Balovaptan | Day 1 of Period 1 | 0.25 Hour |
| Cohort 1 | Time to Maximum Observed Plasma Concentration (Tmax) of IV Balovaptan | Day 14 of Period 2 | 0.25 Hour |
| Cohort 2 | Time to Maximum Observed Plasma Concentration (Tmax) of IV Balovaptan | Day 1 of Period 1 | 0.25 Hour |
| Cohort 2 | Time to Maximum Observed Plasma Concentration (Tmax) of IV Balovaptan | Day 14 of Period 2 | 0.25 Hour |
Secondary
Tlast of M2 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Tlast of M2 Metabolites | Day 1 of Period 1 | 120.00 Hour |
| Cohort 1 | Tlast of M2 Metabolites | Day 14 of Period 1 | 108.00 Hour |
| Cohort 2 | Tlast of M2 Metabolites | Day 1 of Period 1 | 168.00 Hour |
| Cohort 2 | Tlast of M2 Metabolites | Day 14 of Period 1 | 108.00 Hour |
Secondary
Tlast of M3 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Tlast of M3 Metabolites | Day 1 of Period 1 | 216.00 Hour |
| Cohort 1 | Tlast of M3 Metabolites | Day 14 of Period 2 | 108.00 Hour |
| Cohort 2 | Tlast of M3 Metabolites | Day 1 of Period 1 | 216.00 Hour |
| Cohort 2 | Tlast of M3 Metabolites | Day 14 of Period 2 | 108.00 Hour |
Secondary
Tlast of Oral Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Tlast of Oral Balovaptan | Day 1 of Period 1 | 132.00 Hour |
| Cohort 1 | Tlast of Oral Balovaptan | Day 14 of Period 2 | 108.00 Hour |
| Cohort 2 | Tlast of Oral Balovaptan | Day 1 of Period 1 | 156.00 Hour |
| Cohort 2 | Tlast of Oral Balovaptan | Day 14 of Period 2 | 108.00 Hour |
Secondary
Tmax of M2 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Tmax of M2 Metabolites | Day 1 of Period 1 | 24.0 Hour |
| Cohort 1 | Tmax of M2 Metabolites | Day 14 of Period 2 | 4.50 Hour |
| Cohort 2 | Tmax of M2 Metabolites | Day 1 of Period 1 | 24.0 Hour |
| Cohort 2 | Tmax of M2 Metabolites | Day 14 of Period 2 | 3.38 Hour |
Secondary
Tmax of M3 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Tmax of M3 Metabolites | Day 1 of Period 1 | 48.0 Hour |
| Cohort 1 | Tmax of M3 Metabolites | Day 14 of Period 2 | 2.13 Hour |
| Cohort 2 | Tmax of M3 Metabolites | Day 1 of Period 1 | 12.0 Hour |
| Cohort 2 | Tmax of M3 Metabolites | Day 14 of Period 2 | 1.88 Hour |
Secondary
Tmax of Oral Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Tmax of Oral Balovaptan | Day 14 of Period 2 | 1.28 Hour |
| Cohort 1 | Tmax of Oral Balovaptan | Day 1 of Period 1 | 1.23 Hour |
| Cohort 2 | Tmax of Oral Balovaptan | Day 1 of Period 1 | 1.00 Hour |
| Cohort 2 | Tmax of Oral Balovaptan | Day 14 of Period 2 | 1.11 Hour |
Secondary
Total Body Clearance (CL) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Total Body Clearance (CL) of IV Balovaptan | Day 1 of Period 1 | 9.98 L/h | Geometric Coefficient of Variation 34.1 |
| Cohort 1 | Total Body Clearance (CL) of IV Balovaptan | Day 14 of Period 2 | 6.23 L/h | Geometric Coefficient of Variation 71.4 |
| Cohort 2 | Total Body Clearance (CL) of IV Balovaptan | Day 1 of Period 1 | 9.75 L/h | Geometric Coefficient of Variation 20.4 |
| Cohort 2 | Total Body Clearance (CL) of IV Balovaptan | Day 14 of Period 2 | 9.36 L/h | Geometric Coefficient of Variation 27.1 |
Secondary
Volume of Distribution (Vss) of IV Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Volume of Distribution (Vss) of IV Balovaptan | Day 1 of Period 1 | 396 Liter | Geometric Coefficient of Variation 53.1 |
| Cohort 1 | Volume of Distribution (Vss) of IV Balovaptan | Day 14 of Period 2 | 166 Liter | Geometric Coefficient of Variation 95.4 |
| Cohort 2 | Volume of Distribution (Vss) of IV Balovaptan | Day 1 of Period 1 | 197 Liter | Geometric Coefficient of Variation 21.9 |
| Cohort 2 | Volume of Distribution (Vss) of IV Balovaptan | Day 14 of Period 2 | 154 Liter | Geometric Coefficient of Variation 15.3 |
Secondary
λz of M2 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | λz of M2 Metabolites | Day 1 of Period 1 | 0.0143 /hour | Geometric Coefficient of Variation 36.7 |
| Cohort 1 | λz of M2 Metabolites | Day 14 of Period 2 | 0.0191 /hour | Geometric Coefficient of Variation 25 |
| Cohort 2 | λz of M2 Metabolites | Day 1 of Period 1 | 0.0194 /hour | Geometric Coefficient of Variation 27.2 |
| Cohort 2 | λz of M2 Metabolites | Day 14 of Period 2 | 0.0244 /hour | Geometric Coefficient of Variation 13.5 |
Secondary
λz of M3 Metabolites
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | λz of M3 Metabolites | Day 1 of Period 1 | 0.0075 /hour | Geometric Coefficient of Variation 18.5 |
| Cohort 1 | λz of M3 Metabolites | Day 14 of Period 2 | 0.0115 /hour | Geometric Coefficient of Variation 29.1 |
| Cohort 2 | λz of M3 Metabolites | Day 1 of Period 1 | 0.0102 /hour | Geometric Coefficient of Variation 29.8 |
| Cohort 2 | λz of M3 Metabolites | Day 14 of Period 2 | 0.0206 /hour | Geometric Coefficient of Variation 11.2 |
Secondary
λz of Oral Balovaptan
Time frame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Population: The Pharmacokinetic (PK) analysis population consisted of all participants who received at least one dose of balovaptan. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | λz of Oral Balovaptan | Day 1 of Period 1 | 0.0179 /h | Geometric Coefficient of Variation 25.9 |
| Cohort 1 | λz of Oral Balovaptan | Day 14 of Period 2 | 0.0222 /h | Geometric Coefficient of Variation 15.6 |
| Cohort 2 | λz of Oral Balovaptan | Day 1 of Period 1 | 0.0239 /h | Geometric Coefficient of Variation 28.7 |
| Cohort 2 | λz of Oral Balovaptan | Day 14 of Period 2 | 0.0306 /h | Geometric Coefficient of Variation 15.7 |