A Study Investigating the Absolute Oral Bioavailability o... | NCT03764449

Label	Type	Description	Intervention Names
Cohort 1	Experimental	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.	Drug: Oral Balovaptan Drug: IV Balovaptan
Cohort 2	Experimental	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.	Drug: Oral Balovaptan Drug: IV Balovaptan

Name	Type	Description	Arm Group Labels	Other Names
Oral Balovaptan	Drug	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.	Cohort 1

Measure	Description	Time Frame
Absolute Bioavailability of Oral Balovaptan at Dose Level A (Cohort 1)	Absolute oral bioavailability of a single dose A of balovaptan.	Day 1 of Period 1 (Period 1 is 14 days).

Measure	Description	Time Frame
Absolute Bioavailability of Oral Balovaptan at Dose Level B (Cohort 2)	Absolute oral bioavailability of a single dose B balovaptan.	Day 1 of Period 1 (Period 1 is 14 days).
Absolute Bioavailability of Oral Balovaptan at Dose A and Dose B

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pra International Group B.V		Groningen		9728 NZ	Netherlands

PubMed Identifier	Type	Citation	Retractions
34176392	Derived	Derks M, Lennon-Chrimes S, Guenther A, Squassante L, Wandel C, Szczesny P, Paehler A, Kletzl H. Bioavailability and pharmacokinetic profile of balovaptan, a selective, brain-penetrant vasopressin 1a receptor antagonist, in healthy volunteers. Expert Opin Investig Drugs. 2021 Aug;30(8):893-901. doi: 10.1080/13543784.2021.1948009. Epub 2021 Jul 16.

ID	Title	Description
FG000	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.
FG001	Cohort 2

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 22, 2018	Feb 10, 2020

Primary

Absolute Bioavailability of Oral Balovaptan at Dose Level A (Cohort 1)

Absolute oral bioavailability of a single dose A of balovaptan.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Percentage

Day 1 of Period 1 (Period 1 is 14 days).

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG0008

Title

Denominators

Categories

Title	Measurements
	OG000100.6± 31.4

Secondary

Absolute Bioavailability of Oral Balovaptan at Dose Level B (Cohort 2)

Absolute oral bioavailability of a single dose B balovaptan.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Percentage

Day 1 of Period 1 (Period 1 is 14 days).

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Percentage

Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

Maximum Plasma Concentration (Cmax) of IV Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

pg/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Cmax of Oral Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Cmax of M2 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Cmax of M3 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Time to Maximum Observed Plasma Concentration (Tmax) of IV Balovaptan

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.

Posted

Median

Full Range

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Tmax of Oral Balovaptan

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.

Posted

Median

Full Range

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Tmax of M2 Metabolites

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.

Posted

Median

Full Range

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Tmax of M3 Metabolites

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.

Posted

Median

Full Range

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Apparent Terminal Half-Life (t1/2) of IV Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

T1/2 of Oral Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

T1/2 of M2 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

T1/2 of M3 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Plasma Concentration Time Point (AUC0-last) of IV Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*pg/mL

Day 1 of Period 1 (Period 1 is 14 days)

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

AUC0-last of Oral Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1 of Period 1 (Period 1 is 14 days)

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

AUC0-last of M2 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1 of Period 1 (Period 1 is 14 days)

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

AUC0-last of M3 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1 of Period 1 (Period 1 is 14 days)

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of IV Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*pg/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

AUC0-inf of Oral Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1 of Period 1 (Period 1 is 14 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

AUC0-inf of M2 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1 of Period 1 (Period 1 is 14 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

AUC0-inf of M3 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1 of Period 1 (Period 1 is 14 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUC0-24) of IV Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*pg/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

AUC0-24 of Oral Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

AUC0-24 of M2 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

AUC0-24 of M3 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Last Measurable Plasma Concentration (Clast) of IV Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

pg/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Clast of Oral Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Clast of M2 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Clast of M3 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Time of Last Measurable Plasma Concentration (Tlast) of IV Balovaptan

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.

Posted

Median

Full Range

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Tlast of Oral Balovaptan

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.

Posted

Median

Full Range

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Tlast of M2 Metabolites

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.

Posted

Median

Full Range

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Tlast of M3 Metabolites

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.

Posted

Median

Full Range

Hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Terminal Elimination Rate Constant (λz) of IV Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

/hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

λz of Oral Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

/h

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

λz of M2 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

/hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

λz of M3 Metabolites

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

/hour

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Total Body Clearance (CL) of IV Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

L/h

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Volume of Distribution (Vss) of IV Balovaptan

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liter

Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Treatment-Emergent Adverse Events

The safety analysis population consisted of participants who received at least one dose of balovaptan.

Posted

Number

Percentage

Up to 35 days from screening (sceening is up to 28 days prior to admission to the clinical research unit).

ID	Title	Description
OG000	Cohort 1, Period 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.
OG001	Cohort 1, Period 2	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.
OG002	Cohort 2, Period 1	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.
OG003	Cohort 2, Period 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.

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1 Period 1	Balovaptan was administered at dose level A as a single oral dose. IV infusion of balovaptan was administered after the balovaptan oral dose.	8	8	4	8
EG001	Cohort 1, Period 2	Balovaptan was administered at dose level A as an oral dose once daily on Day 1 to Day 14. IV infusion of balovaptan was administered after the final oral dose of balovaptan.	8	8	6	8
EG002	Cohort 2, Period 1	Balovaptan was administered as a single oral dose at dose level B. IV infusion of balovaptan was administered after the balovaptan oral dose.	8	8	5	8
EG003	Cohort 2, Period 2	Balovaptan was administered at Dose level B as an oral dose once daily on Day 1 to Day 14. IV infusion of balovaptan was administered after the final oral dose of balovaptan.	8	8	7	8

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Ear congestion	Ear and labyrinth disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG0031 events1 affected8 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA version 21.1	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 21.1	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA version 21.1	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Catheter site erythema	General disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Catheter site haematoma	General disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected8 at risk EG0020 events0 affected8 at risk EG003
Catheter site pain	General disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0014 events3 affected8 at risk EG0020 events0 affected8 at risk EG003
Catheter site swelling	General disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0022 events2 affected8 at risk EG003
Fatigue	General disorders	MedDRA version 21.1	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Infusion site pain	General disorders	MedDRA version 21.1	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected8 at risk EG0021 events1 affected8 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events1 affected8 at risk EG0020 events0 affected8 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected8 at risk EG0020 events0 affected8 at risk EG003
Dizziness	Nervous system disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0021 events1 affected8 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA version 21.1	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Headache	Nervous system disorders	MedDRA version 21.1	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0022 events2 affected8 at risk EG003
Insomnia	Psychiatric disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Mood altered	Psychiatric disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Nightmare	Psychiatric disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected8 at risk EG0020 events0 affected8 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0021 events1 affected8 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0022 events2 affected8 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected8 at risk EG0020 events0 affected8 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA version 21.1	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected8 at risk EG0020 events0 affected8 at risk EG003
Haematoma	Vascular disorders	MedDRA version 21.1	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups