Trial Outcomes & Findings for A Study to Investigate the Effect of Esomeprazole and the Effect of Food on the Pharmacokinetics of Balovaptan in Healthy Volunteers (NCT NCT04156646)

NCT ID: NCT04156646

Last Updated: 2021-03-16

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 16 participants
• Primary outcome timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
• Results posted on: 2021-03-16

Participant Flow

Screening was conducted between Day -28 and Day -2.

Participant milestones

Measure	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	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
Treatment Period 1 (6 Days) STARTED	8	8
Treatment Period 1 (6 Days) COMPLETED	8	8
Treatment Period 1 (6 Days) NOT COMPLETED	0	0
Wash-out Period (12- to 21-days) STARTED	8	8
Wash-out Period (12- to 21-days) COMPLETED	8	8
Wash-out Period (12- to 21-days) NOT COMPLETED	0	0
Treatment Period 2 (6 Days) STARTED	8	8
Treatment Period 2 (6 Days) COMPLETED	8	8
Treatment Period 2 (6 Days) NOT COMPLETED	0	0
Treatment Period 3 (6 Days) STARTED	8	8
Treatment Period 3 (6 Days) COMPLETED	8	7
Treatment Period 3 (6 Days) NOT COMPLETED	0	1

Reasons for withdrawal

Measure	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	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
Treatment Period 3 (6 Days) Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treatment Sequence ABC n=8 Participants 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	Treatment Sequence BAC n=8 Participants Participants were randomized to BAC sequence on Day 1 of Period 1 with the treatments being as follows: * Treatment B: 20 mg balovaptan administered as a single oral dose after a ≥10-hour fast * Treatment A: 20 mg balovaptan administered as a single oral dose following consumption of high-fat, high-calorie meal * Treatment C: 40 mg esomeprazole administered once daily (QD) for 6 days and with a single dose of balovaptan 20 mg in the fasted state 1 hour after the fifth esomeprazole dose	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=113 Participants	8 Participants n=163 Participants	16 Participants n=160 Participants
Age, Categorical >=65 years	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Age, Continuous	39.3 Years STANDARD_DEVIATION 11.96 • n=113 Participants	47.1 Years STANDARD_DEVIATION 13.26 • n=163 Participants	43.2 Years STANDARD_DEVIATION 12.9 • n=160 Participants
Sex: Female, Male Female	4 Participants n=113 Participants	1 Participants n=163 Participants	5 Participants n=160 Participants
Sex: Female, Male Male	4 Participants n=113 Participants	7 Participants n=163 Participants	11 Participants n=160 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=113 Participants	1 Participants n=163 Participants	2 Participants n=160 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=113 Participants	7 Participants n=163 Participants	14 Participants n=160 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Race (NIH/OMB) Asian	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Race (NIH/OMB) Black or African American	3 Participants n=113 Participants	4 Participants n=163 Participants	7 Participants n=160 Participants
Race (NIH/OMB) White	5 Participants n=113 Participants	3 Participants n=163 Participants	8 Participants n=160 Participants
Race (NIH/OMB) More than one race	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=113 Participants	1 Participants n=163 Participants	1 Participants n=160 Participants

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Maximum Plasma Concentration (Cmax) of Balovaptan	74.83 ng/mL Geometric Coefficient of Variation 42.6	97.44 ng/mL Geometric Coefficient of Variation 44.6	79.67 ng/mL Geometric Coefficient of Variation 38.3

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=15 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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	1705.7 h*ng/mL Geometric Coefficient of Variation 55.9	1820.0 h*ng/mL Geometric Coefficient of Variation 46.9

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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	945.2 h*ng/mL Geometric Coefficient of Variation 30.8	965.0 h*ng/mL Geometric Coefficient of Variation 30.7

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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	1636.1 h*ng/mL Geometric Coefficient of Variation 53.3	1650.9 h*ng/mL Geometric Coefficient of Variation 48.3

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Time to Reach Cmax in Plasma (Tmax) of Balovaptan	4.50 h Interval 0.5 to 8.0	1.00 h Interval 0.5 to 3.0	1.75 h Interval 1.0 to 4.0

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Last Quantifiable Concentration (Clast) of Balovaptan	1.693 ng/mL Geometric Coefficient of Variation 45.2	1.745 ng/mL Geometric Coefficient of Variation 57.3	2.253 ng/mL Geometric Coefficient of Variation 142.8

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Time To the Last Quantifiable Concentration (Tlast) of Balovaptan	115.86 h Geometric Coefficient of Variation 33.4	113.79 h Geometric Coefficient of Variation 35.0	103.58 h Geometric Coefficient of Variation 41.0

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Time Between Dosing and Time of First Balovaptan Plasma Concentration (Tlag)	0.2500 h Interval 0.0 to 1.5	0.2500 h Interval 0.0 to 0.5	0.2500 h Interval 0.0 to 0.5

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Apparent Clearance (Cl/F) of Balovaptan	11.51 L/h Geometric Coefficient of Variation 35.7	11.73 L/h Geometric Coefficient of Variation 36.3	11.26 L/h Geometric Coefficient of Variation 32.2

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Apparent Volume of Distribution (Vd/F) of Balovaptan	422.7 L Geometric Coefficient of Variation 28.7	422.5 L Geometric Coefficient of Variation 33.4	429.4 L Geometric Coefficient of Variation 18.5

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=15 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Terminal Elimination Phase Half-Life (T1/2) of Balovaptan	25.44 h Geometric Coefficient of Variation 40.0	24.98 h Geometric Coefficient of Variation 47.0	27.26 h Geometric Coefficient of Variation 40.9

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Terminal Phase Rate Constant (λz) of Balovaptan	0.0272 /h Geometric Coefficient of Variation 33.3	0.0278 /h Geometric Coefficient of Variation 37.5	0.0263 /h Geometric Coefficient of Variation 30.3

PRIMARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Population: Number of analyzed participants reflects number of participants whose samples were available at given timepoint.

Amount of Balovaptan in a given volume of plasma.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Plasma Concentrations of Balovaptan 2 Hrs Postdose	27.47 ng/mL Geometric Coefficient of Variation 77.0	70.75 ng/mL Geometric Coefficient of Variation 32.9	62.24 ng/mL Geometric Coefficient of Variation 37.0
Plasma Concentrations of Balovaptan 2.5 Hrs Postdose	32.90 ng/mL Geometric Coefficient of Variation 73.0	66.40 ng/mL Geometric Coefficient of Variation 33.4	63.44 ng/mL Geometric Coefficient of Variation 32.1
Plasma Concentrations of Balovaptan 3 Hrs Postdose	41.92 ng/mL Geometric Coefficient of Variation 73.6	63.60 ng/mL Geometric Coefficient of Variation 29.7	66.26 ng/mL Geometric Coefficient of Variation 29.8
Plasma Concentrations of Balovaptan 3.5 Hrs Postdose	45.68 ng/mL Geometric Coefficient of Variation 60.4	60.63 ng/mL Geometric Coefficient of Variation 31.2	64.70 ng/mL Geometric Coefficient of Variation 34.5
Plasma Concentrations of Balovaptan 4 Hrs Postdose	51.84 ng/mL Geometric Coefficient of Variation 50.2	59.58 ng/mL Geometric Coefficient of Variation 27.9	63.95 ng/mL Geometric Coefficient of Variation 31.5
Plasma Concentrations of Balovaptan 5 Hrs Postdose	60.59 ng/mL Geometric Coefficient of Variation 36.5	59.56 ng/mL Geometric Coefficient of Variation 27.4	61.45 ng/mL Geometric Coefficient of Variation 35.4
Plasma Concentrations of Balovaptan 6 Hrs Postdose	56.91 ng/mL Geometric Coefficient of Variation 34.6	49.69 ng/mL Geometric Coefficient of Variation 28.3	54.51 ng/mL Geometric Coefficient of Variation 31.1
Plasma Concentrations of Balovaptan 8 Hrs Postdose	51.07 ng/mL Geometric Coefficient of Variation 30.7	44.58 ng/mL Geometric Coefficient of Variation 30.0	48.05 ng/mL Geometric Coefficient of Variation 30.5
Plasma Concentrations of Balovaptan 12 Hrs Postdose	39.18 ng/mL Geometric Coefficient of Variation 27.4	34.74 ng/mL Geometric Coefficient of Variation 32.9	35.91 ng/mL Geometric Coefficient of Variation 31.8
Plasma Concentrations of Balovaptan 16 Hrs Postdose	33.17 ng/mL Geometric Coefficient of Variation 38.5	28.88 ng/mL Geometric Coefficient of Variation 37.5	30.85 ng/mL Geometric Coefficient of Variation 37.1
Plasma Concentrations of Balovaptan 24 Hrs Postdose	25.43 ng/mL Geometric Coefficient of Variation 42.7	22.95 ng/mL Geometric Coefficient of Variation 43.6	25.95 ng/mL Geometric Coefficient of Variation 37.2
Plasma Concentrations of Balovaptan 36 Hrs Postdose	14.94 ng/mL Geometric Coefficient of Variation 57.1	13.92 ng/mL Geometric Coefficient of Variation 55.4	15.13 ng/mL Geometric Coefficient of Variation 50.1
Plasma Concentrations of Balovaptan 48 Hrs Postdose	9.75 ng/mL Geometric Coefficient of Variation 70.5	10.70 ng/mL Geometric Coefficient of Variation 7.376	12.15 ng/mL Geometric Coefficient of Variation 6.794
Plasma Concentrations of Balovaptan 72 Hrs Postdose	4.47 ng/mL Geometric Coefficient of Variation 90.2	4.28 ng/mL Geometric Coefficient of Variation 97.8	5.04 ng/mL Geometric Coefficient of Variation 64.0
Plasma Concentrations of Balovaptan 96 Hrs Postdose	2.68 ng/mL Geometric Coefficient of Variation 112.0	2.86 ng/mL Geometric Coefficient of Variation 125.0	2.98 ng/mL Geometric Coefficient of Variation 91.4
Plasma Concentrations of Balovaptan 144 Hrs Postdose	2.38 ng/mL Geometric Coefficient of Variation 186.5	2.45 ng/mL Geometric Coefficient of Variation 204.4	2.57 ng/mL Geometric Coefficient of Variation 198.5
Plasma Concentrations of Balovaptan 192 Hrs Postdose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)
Plasma Concentrations of Balovaptan Predose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)
Plasma Concentrations of Balovaptan 0.25 Hrs Postdose	3.90 ng/mL Geometric Coefficient of Variation 246.8	2.46 ng/mL Geometric Coefficient of Variation 136.0	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)
Plasma Concentrations of Balovaptan 0.5 Hrs Postdose	8.89 ng/mL Geometric Coefficient of Variation 235.7	21.26 ng/mL Geometric Coefficient of Variation 117.5	8.40 ng/mL Geometric Coefficient of Variation 129.8
Plasma Concentrations of Balovaptan 1 Hrs Postdose	17.76 ng/mL Geometric Coefficient of Variation 113.0	63.58 ng/mL Geometric Coefficient of Variation 60.9	44.78 ng/mL Geometric Coefficient of Variation 70.8
Plasma Concentrations of Balovaptan 1.5 Hrs Postdose	20.08 ng/mL Geometric Coefficient of Variation 88.2	66.54 ng/mL Geometric Coefficient of Variation 47.4	49.82 ng/mL Geometric Coefficient of Variation 52.7

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Maximum Plasma Concentration (Cmax) of M2 Metabolite	11.27 ng/mL Geometric Coefficient of Variation 27.0	11.44 ng/mL Geometric Coefficient of Variation 30.8	11.68 ng/mL Geometric Coefficient of Variation 30.1

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Maximum Plasma Concentration (Cmax) of M3 Metabolite	15.96 ng/mL Geometric Coefficient of Variation 37.0	16.91 ng/mL Geometric Coefficient of Variation 40.8	16.85 ng/mL Geometric Coefficient of Variation 32.3

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Maximum Plasma Concentration (Cmax) of Esomeprazole	1255.2 ng/mL Geometric Coefficient of Variation 36.9	—	—

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=15 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=14 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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	998.5 h*ng/mL Geometric Coefficient of Variation 22.7	1087.7 h*ng/mL Geometric Coefficient of Variation 21.9

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=13 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=13 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=11 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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	1590.0 h*ng/mL Geometric Coefficient of Variation 26.9	1723.2 h*ng/mL Geometric Coefficient of Variation 26.5

SECONDARY outcome

Timeframe: 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%.

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=13 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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 outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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	180.1 h*ng/mL Geometric Coefficient of Variation 39.5	182.2 h*ng/mL Geometric Coefficient of Variation 35.9

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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	325.1 h*ng/mL Geometric Coefficient of Variation 42.0	325.5 h*ng/mL Geometric Coefficient of Variation 34.1

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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	869.4 h*ng/mL Geometric Coefficient of Variation 26.9	873.9 h*ng/mL Geometric Coefficient of Variation 32.8

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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	1462.8 h*ng/mL Geometric Coefficient of Variation 29.3	1384.3 h*ng/mL Geometric Coefficient of Variation 35.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
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 outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Time to Reach Cmax in Plasma (Tmax) of M2 Metabolite	36.00 h Interval 16.0 to 48.0	24.03 h Interval 16.0 to 48.0	36.00 h Interval 12.0 to 48.0

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Time to Reach Cmax in Plasma (Tmax) of M3 Metabolite	20.01 h Interval 12.0 to 36.0	24.02 h Interval 4.0 to 36.0	16.00 h Interval 5.0 to 36.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Time to Reach Cmax in Plasma (Tmax) of Esomeprazole	2.00 h Interval 1.5 to 4.0	—	—

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Last Quantifiable Concentration (Clast) of M2 Metabolite	1.515 ng/mL Geometric Coefficient of Variation 30.0	1.739 ng/mL Geometric Coefficient of Variation 29.4	1.682 ng/mL Geometric Coefficient of Variation 82.8

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Last Quantifiable Concentration (Clast) of M3 Metabolite	2.211 ng/mL Geometric Coefficient of Variation 46.2	2.279 ng/mL Geometric Coefficient of Variation 55.4	2.837 ng/mL Geometric Coefficient of Variation 82.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Last Quantifiable Concentration (Clast) of Esomeprazole	133.3 ng/mL Geometric Coefficient of Variation 78.8	—	—

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Time To the Last Quantifiable Concentration (Tlast) of M2 Metabolite	155.3 h Geometric Coefficient of Variation 21.2	142.4 h Geometric Coefficient of Variation 25.2	142.4 h Geometric Coefficient of Variation 29.5

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Time To the Last Quantifiable Concentration (Tlast) of M3 Metabolite	192.0 h Geometric Coefficient of Variation 0.0	192.0 h Geometric Coefficient of Variation 0.0	168.7 h Geometric Coefficient of Variation 23.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Time To the Last Quantifiable Concentration (Tlast) of Esomeprazole	8.002 h Geometric Coefficient of Variation 0.1	—	—

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=15 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=14 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Terminal Elimination Phase Half-Life (T1/2) of M2 Metabolite	38.99 h Geometric Coefficient of Variation 29.2	37.81 h Geometric Coefficient of Variation 30.7	39.19 h Geometric Coefficient of Variation 22.7

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

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.

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=13 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=13 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=11 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Terminal Elimination Phase Half-Life (T1/2) of M3 Metabolite	57.40 h Geometric Coefficient of Variation 17.3	59.30 h Geometric Coefficient of Variation 17.6	57.81 h Geometric Coefficient of Variation 19.2

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=13 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Terminal Elimination Phase Half-Life (T1/2) of Esomeprazole	1.590 h Geometric Coefficient of Variation 29.2	—	—

SECONDARY outcome

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Percentage of Patricipants With Adverse Events (AEs)	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Population: For one participant there was no terminal phase, so they are excluded form the analysis.

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=15 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Terminal Phase Rate Constant (λz) of M2 Metabolite	0.0178 /h Geometric Coefficient of Variation 30.3	0.0174 /h Geometric Coefficient of Variation 31.9	0.0171 /h Geometric Coefficient of Variation 25.5

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Population: For one participant there was no terminal phase, so they are excluded form the analysis.

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=15 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Terminal Phase Rate Constant (λz) of M3 Metabolite	0.0112 /h Geometric Coefficient of Variation 22.1	0.0107 /h Geometric Coefficient of Variation 24.8	0.0107 /h Geometric Coefficient of Variation 25.2

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Balovaptan 20 mg Fed n=14 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Terminal Phase Rate Constant (λz) of Esomeprazole	0.4197 /h Geometric Coefficient of Variation 30.1	—	—

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Population: Number of analyzed participants reflects number of participants whose samples were available at given timepoint.

Amount of M2 Analyte in a given volume of plasma.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Plasma Concentrations of M2 Analyte 8 Hrs Postdose	5.223 ng/mL Geometric Coefficient of Variation 48.9	6.550 ng/mL Geometric Coefficient of Variation 46.6	6.512 ng/mL Geometric Coefficient of Variation 40.8
Plasma Concentrations of M2 Analyte 12 Hrs Postdose	6.921 ng/mL Geometric Coefficient of Variation 40.4	7.889 ng/mL Geometric Coefficient of Variation 39.5	8.426 ng/mL Geometric Coefficient of Variation 42.9
Plasma Concentrations of M2 Analyte 16 Hrs Postdose	8.384 ng/mL Geometric Coefficient of Variation 39.7	9.207 ng/mL Geometric Coefficient of Variation 40.9	9.563 ng/mL Geometric Coefficient of Variation 34.2
Plasma Concentrations of M2 Analyte 24 Hrs Postdose	10.123 ng/mL Geometric Coefficient of Variation 29.4	10.928 ng/mL Geometric Coefficient of Variation 30.9	10.887 ng/mL Geometric Coefficient of Variation 33.0
Plasma Concentrations of M2 Analyte 36 Hrs Postdose	10.509 ng/mL Geometric Coefficient of Variation 29.6	10.519 ng/mL Geometric Coefficient of Variation 27.4	11.409 ng/mL Geometric Coefficient of Variation 26.9
Plasma Concentrations of M2 Analyte Predose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)
Plasma Concentrations of M2 Analyte 0.25 Hrs Postdose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)
Plasma Concentrations of M2 Analyte 0.5 Hrs Postdose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)
Plasma Concentrations of M2 Analyte 1 Hrs Postdose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	3.081 ng/mL Geometric Coefficient of Variation 62.2	2.649 ng/mL Geometric Coefficient of Variation 95.5
Plasma Concentrations of M2 Analyte 1.5 Hrs Postdose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	3.421 ng/mL Geometric Coefficient of Variation 57.2	2.690 ng/mL Geometric Coefficient of Variation 72.6
Plasma Concentrations of M2 Analyte 2 Hrs Postdose	2.021 ng/mL Geometric Coefficient of Variation 97.7	3.637 ng/mL Geometric Coefficient of Variation 45.6	3.019 ng/mL Geometric Coefficient of Variation 54.9
Plasma Concentrations of M2 Analyte 2.5 Hrs Postdose	2.236 ng/mL Geometric Coefficient of Variation 83.3	3.724 ng/mL Geometric Coefficient of Variation 48.8	3.502 ng/mL Geometric Coefficient of Variation 46.4
Plasma Concentrations of M2 Analyte 3 Hrs Postdose	2.714 ng/mL Geometric Coefficient of Variation 80.0	4.293 ng/mL Geometric Coefficient of Variation 49.9	3.878 ng/mL Geometric Coefficient of Variation 43.2
Plasma Concentrations of M2 Analyte 4 Hrs Postdose	3.208 ng/mL Geometric Coefficient of Variation 65.5	4.860 ng/mL Geometric Coefficient of Variation 49.1	4.749 ng/mL Geometric Coefficient of Variation 41.1
Plasma Concentrations of M2 Analyte 5 Hrs Postdose	3.756 ng/mL Geometric Coefficient of Variation 60.5	5.696 ng/mL Geometric Coefficient of Variation 47.9	5.471 ng/mL Geometric Coefficient of Variation 44.8
Plasma Concentrations of M2 Analyte 6 Hrs Postdose	4.158 ng/mL Geometric Coefficient of Variation 50.9	5.797 ng/mL Geometric Coefficient of Variation 50.0	5.775 ng/mL Geometric Coefficient of Variation 39.8
Plasma Concentrations of M2 Analyte 3.5 Hrs Postdose	2.780 ng/mL Geometric Coefficient of Variation 75.7	4.724 ng/mL Geometric Coefficient of Variation 49.2	4.217 ng/mL Geometric Coefficient of Variation 44.5
Plasma Concentrations of M2 Analyte 48 Hrs Postdose	9.383 ng/mL Geometric Coefficient of Variation 28.2	9.134 ng/mL Geometric Coefficient of Variation 25.8	10.191 ng/mL Geometric Coefficient of Variation 26.8
Plasma Concentrations of M2 Analyte 72 Hrs Postdose	6.576 ng/mL Geometric Coefficient of Variation 30.7	5.998 ng/mL Geometric Coefficient of Variation 27.5	27.5 ng/mL Geometric Coefficient of Variation 23.5
Plasma Concentrations of M2 Analyte 96 Hrs Postdose	4.050 ng/mL Geometric Coefficient of Variation 41.6	3.748 ng/mL Geometric Coefficient of Variation 32.9	4.450 ng/mL Geometric Coefficient of Variation 27.5
Plasma Concentrations of M2 Analyte 144 Hrs Postdose	2.033 ng/mL Geometric Coefficient of Variation 64.7	2.139 ng/mL Geometric Coefficient of Variation 71.9	2.107 ng/mL Geometric Coefficient of Variation 45.2
Plasma Concentrations of M2 Analyte 192 Hrs Postdose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)

SECONDARY outcome

Timeframe: Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Population: Number of analyzed participants reflects number of participants whose samples were available at given timepoint.

Amount of M3 Analyte in a given volume of plasma.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Plasma Concentrations of M3 Analyte Predose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)
Plasma Concentrations of M3 Analyte 0.25 Hrs Postdose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)
Plasma Concentrations of M3 Analyte 0.5 Hrs Postdose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 1.00 ng/mL)	5.006 ng/mL Geometric Coefficient of Variation 118.0	3.172 ng/mL Geometric Coefficient of Variation 127.1
Plasma Concentrations of M3 Analyte 1 Hrs Postdose	2.347 ng/mL Geometric Coefficient of Variation 138.4	7.812 ng/mL Geometric Coefficient of Variation 60.6	5.556 ng/mL Geometric Coefficient of Variation 78.9
Plasma Concentrations of M3 Analyte 1.5 Hrs Postdose	3.787 ng/mL Geometric Coefficient of Variation 95.1	8.928 ng/mL Geometric Coefficient of Variation 59.6	6.705 ng/mL Geometric Coefficient of Variation 62.6
Plasma Concentrations of M3 Analyte 2 Hrs Postdose	5.211 ng/mL Geometric Coefficient of Variation 83.0	10.157 ng/mL Geometric Coefficient of Variation 46.8	8.859 ng/mL Geometric Coefficient of Variation 55.8
Plasma Concentrations of M3 Analyte 2.5 Hrs Postdose	5.520 ng/mL Geometric Coefficient of Variation 83.5	10.539 ng/mL Geometric Coefficient of Variation 47.9	9.853 ng/mL Geometric Coefficient of Variation 45.8
Plasma Concentrations of M3 Analyte 3 Hrs Postdose	6.616 ng/mL Geometric Coefficient of Variation 85.9	10.980 ng/mL Geometric Coefficient of Variation 48.6	10.887 ng/mL Geometric Coefficient of Variation 39.4
Plasma Concentrations of M3 Analyte 3.5 Hrs Postdose	5.985 ng/mL Geometric Coefficient of Variation 78.0	11.369 ng/mL Geometric Coefficient of Variation 50.8	11.316 ng/mL Geometric Coefficient of Variation 41.2
Plasma Concentrations of M3 Analyte 4 Hrs Postdose	6.408 ng/mL Geometric Coefficient of Variation 71.4	12.160 ng/mL Geometric Coefficient of Variation 50.8	11.969 ng/mL Geometric Coefficient of Variation 38.0
Plasma Concentrations of M3 Analyte 5 Hrs Postdose	8.901 ng/mL Geometric Coefficient of Variation 58.8	13.241 ng/mL Geometric Coefficient of Variation 41.5	12.998 ng/mL Geometric Coefficient of Variation 46.7
Plasma Concentrations of M3 Analyte 6 Hrs Postdose	9.691 ng/mL Geometric Coefficient of Variation 59.8	12.831 ng/mL Geometric Coefficient of Variation 47.9	13.442 ng/mL Geometric Coefficient of Variation 39.6
Plasma Concentrations of M3 Analyte 8 Hrs Postdose	11.157 ng/mL Geometric Coefficient of Variation 47.8	13.875 ng/mL Geometric Coefficient of Variation 48.4	13.762 ng/mL Geometric Coefficient of Variation 40.4
Plasma Concentrations of M3 Analyte 12 Hrs Postdose	12.697 ng/mL Geometric Coefficient of Variation 5.7063	14.296 ng/mL Geometric Coefficient of Variation 39.7	14.287 ng/mL Geometric Coefficient of Variation 36.3
Plasma Concentrations of M3 Analyte 16 Hrs Postdose	14.113 ng/mL Geometric Coefficient of Variation 40.9	15.145 ng/mL Geometric Coefficient of Variation 41.6	15.049 ng/mL Geometric Coefficient of Variation 30.1
Plasma Concentrations of M3 Analyte 24 Hrs Postdose	14.388 ng/mL Geometric Coefficient of Variation 33.4	15.061 ng/mL Geometric Coefficient of Variation 39.7	16.092 ng/mL Geometric Coefficient of Variation 29.9
Plasma Concentrations of M3 Analyte 36 Hrs Postdose	13.626 ng/mL Geometric Coefficient of Variation 26.4	14.148 ng/mL Geometric Coefficient of Variation 29.7	13.793 ng/mL Geometric Coefficient of Variation 27.7
Plasma Concentrations of M3 Analyte 48 Hrs Postdose	11.665 ng/mL Geometric Coefficient of Variation 26.4	11.470 ng/mL Geometric Coefficient of Variation 29.0	12.966 ng/mL Geometric Coefficient of Variation 27.3
Plasma Concentrations of M3 Analyte 72 Hrs Postdose	8.108 ng/mL Geometric Coefficient of Variation 28.3	8.129 ng/mL Geometric Coefficient of Variation 31.3	9.023 ng/mL Geometric Coefficient of Variation 25.2
Plasma Concentrations of M3 Analyte 96 Hrs Postdose	6.066 ng/mL Geometric Coefficient of Variation 31.6	6.111 ng/mL Geometric Coefficient of Variation 42.4	6.653 ng/mL Geometric Coefficient of Variation 34.1
Plasma Concentrations of M3 Analyte 144 Hrs Postdose	3.525 ng/mL Geometric Coefficient of Variation 45.5	3.747 ng/mL Geometric Coefficient of Variation 45.7	3.957 ng/mL Geometric Coefficient of Variation 45.2
Plasma Concentrations of M3 Analyte 192 Hrs Postdose	2.211 ng/mL Geometric Coefficient of Variation 46.2	2.279 ng/mL Geometric Coefficient of Variation 55.4	2.569 ng/mL Geometric Coefficient of Variation 54.2

SECONDARY outcome

Timeframe: 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.

Amount of Esomeprazole in a given volume of plasma.

Outcome measures

Measure	Balovaptan 20 mg Fed n=16 Participants Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state
Plasma Concentrations of Esomeprazole Predose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 2.00 ng/mL)	—	—
Plasma Concentrations of Esomeprazole 0.25 Hrs Postdose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 2.00 ng/mL)	—	—
Plasma Concentrations of Esomeprazole 0.5 Hrs Postdose	NA ng/mL Geometric Coefficient of Variation NA Below Quantifiable Limit (\< 2.00 ng/mL)	—	—
Plasma Concentrations of Esomeprazole 1 Hrs Postdose	171.8 ng/mL Geometric Coefficient of Variation 171.5	—	—
Plasma Concentrations of Esomeprazole 1.5 Hrs Postdose	242.6 ng/mL Geometric Coefficient of Variation 102.8	—	—
Plasma Concentrations of Esomeprazole 2 Hrs Postdose	697.1 ng/mL Geometric Coefficient of Variation 66.2	—	—
Plasma Concentrations of Esomeprazole 3 Hrs Postdose	984.4 ng/mL Geometric Coefficient of Variation 36.1	—	—
Plasma Concentrations of Esomeprazole 4 Hrs Postdose	770.7 ng/mL Geometric Coefficient of Variation 34.7	—	—
Plasma Concentrations of Esomeprazole 6 Hrs Postdose	336.6 ng/mL Geometric Coefficient of Variation 59.8	—	—
Plasma Concentrations of Esomeprazole 8 Hrs Postdose	133.3 ng/mL Geometric Coefficient of Variation 78.8	—	—

Adverse Events

Balovaptan 20 mg Fed

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Balovaptan 20 mg Fasted

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Balovaptan 20 mg Fed n=16 participants at risk Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were administered following consumption of a high-fat, high-calorie meal (Treatment A).	Balovaptan 20 mg Fasted n=16 participants at risk Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were after a ≥ 10 h fast (Treatment B)	Balovaptan 20 mg Fasted + Esomeprazole 40 mg Fasted n=16 participants at risk Single oral doses of balovaptan 20 mg (1 × 20 mg tablet) were coadministered with esomeprazole 40 mg (Treatment C) in a fasted state.
Eye disorders Eye Pain	0.00% 0/16 • From baseline to end of study (up to approximately 7 weeks)	6.2% 1/16 • Number of events 1 • From baseline to end of study (up to approximately 7 weeks)	0.00% 0/16 • From baseline to end of study (up to approximately 7 weeks)
Infections and infestations Gastroenteritis	0.00% 0/16 • From baseline to end of study (up to approximately 7 weeks)	0.00% 0/16 • From baseline to end of study (up to approximately 7 weeks)	6.2% 1/16 • Number of events 1 • From baseline to end of study (up to approximately 7 weeks)
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/16 • From baseline to end of study (up to approximately 7 weeks)	0.00% 0/16 • From baseline to end of study (up to approximately 7 weeks)	6.2% 1/16 • Number of events 1 • From baseline to end of study (up to approximately 7 weeks)
Nervous system disorders Headache	6.2% 1/16 • Number of events 1 • From baseline to end of study (up to approximately 7 weeks)	0.00% 0/16 • From baseline to end of study (up to approximately 7 weeks)	0.00% 0/16 • From baseline to end of study (up to approximately 7 weeks)

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

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

Restriction type: OTHER