Trial Outcomes & Findings for A Study of OPC-41061 Orally Disintegrating (OD) Tablets Using 2 Different Formulations and 2 Dosing Regimens in Healthy Adult Male Subjects (NCT NCT02994394)

Last Updated: 2021-06-28

Results Overview

Blood sampling for plasma tolvaptan concentration before IMP administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, and 16 hours postdose in each period in Cohort 1 and 2 was performed for pharmacokinetic evaluation.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

84 participants

Primary outcome timeframe

Pre-dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours post-dose

Results posted on

2021-06-28

Participant Flow

This single-center, open-label, randomized, 3-period 3-way, crossover study using 2 different formulations and 2 different dosing regimens investigated bioequivalence between tolvaptan orally disintegrating (OD) and conventional tablets in 84 healthy adult male subjects in 2 cohorts. Bioequivalence between the OD and conventional 15 mg tablets was investigated in Cohort 1. In Cohort 2, bioequivalence between the OD and conventional 30 mg tablets was investigated.

A total of 84 subjects were divided into 2 cohorts of 42 subjects each. The 42 subjects each in 2 cohorts were randomly assigned to the conventional tablet first group, OD tablet with water first group, or OD tablet without water first group according to the randomization code in a 1:1:1 ratio. Forty subjects in Cohort 1 and 41 subjects in Cohort 2 completed the trial.

Participant milestones

Participant milestones
Measure	Cohort 1: Conventional Tablet, Then OD Tablet Without Water, Then OD Tablet With Water Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 1: OD Tablet With Water, Then Conventional Tablet, Then OD Tablet Without Water Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 1: OD Tablet Without Water, Then OD Tablet With Water, Then Conventional Tablet Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 2: Conventional Tablet, Then OD Tablet Without Water, Then OD Tablet With Water Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 2: OD Tablet With Water, Then Conventional Tablet, Then OD Tablet Without Water Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 2: OD Tablet Without Water, Then OD Tablet With Water, Then Conventional Tablet Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.
Period 1 (Days 1 to 3) STARTED	14	14	14	14	14	14
Period 1 (Days 1 to 3) COMPLETED	14	14	13	14	14	14
Period 1 (Days 1 to 3) NOT COMPLETED	0	0	1	0	0	0
Period 2 (Days 4 to 6) STARTED	14	14	13	14	14	14
Period 2 (Days 4 to 6) COMPLETED	14	13	13	14	13	14
Period 2 (Days 4 to 6) NOT COMPLETED	0	1	0	0	1	0
Period 3 (Days 7 and 8) STARTED	14	13	13	14	13	14
Period 3 (Days 7 and 8) COMPLETED	14	13	13	14	13	14
Period 3 (Days 7 and 8) NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Conventional Tablet, Then OD Tablet Without Water, Then OD Tablet With Water Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 1: OD Tablet With Water, Then Conventional Tablet, Then OD Tablet Without Water Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 1: OD Tablet Without Water, Then OD Tablet With Water, Then Conventional Tablet Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 2: Conventional Tablet, Then OD Tablet Without Water, Then OD Tablet With Water Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 2: OD Tablet With Water, Then Conventional Tablet, Then OD Tablet Without Water Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 2: OD Tablet Without Water, Then OD Tablet With Water, Then Conventional Tablet Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.
Period 1 (Days 1 to 3) Adverse Event	0	0	1	0	0	0
Period 2 (Days 4 to 6) Adverse Event	0	1	0	0	1	0

Baseline Characteristics

A Study of OPC-41061 Orally Disintegrating (OD) Tablets Using 2 Different Formulations and 2 Dosing Regimens in Healthy Adult Male Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=42 Participants Subjects received single oral administration of tolvaptan 15 mg in Cohort 1, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Cohort 2 n=42 Participants Subjects received single oral administration of tolvaptan 30 mg in Cohort 2, conventional or OD tablet, with or without water on each administration day in Period 1, Period 2, and Period 3. A washout period of 72 hours was set from postdose in Period 1 until predose in Period 2 and from postdose in Period 2 until predose in Period 3.	Total n=84 Participants Total of all reporting groups
Age, Continuous	24.4 years STANDARD_DEVIATION 4.3 • n=5 Participants	23.5 years STANDARD_DEVIATION 4.8 • n=7 Participants	24.0 years STANDARD_DEVIATION 4.5 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	42 Participants n=7 Participants	84 Participants n=5 Participants
Race/Ethnicity, Customized Japanese	42 Participants n=5 Participants	42 Participants n=7 Participants	84 Participants n=5 Participants
Region of Enrollment Japan	42 Participants n=5 Participants	42 Participants n=7 Participants	84 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours post-dose

Population: Bioequivalence analysis set: all subjects with both AUCt and Cmax values across Period 1, Period 2, and Period 3.

Outcome measures

Outcome measures
Measure	Cohort 1: 15 mg Conventional Tablet n=39 Participants Single oral administration of 1 tolvaptan 15 mg conventional tablet with water under fasting conditions	Cohort 1: 15 mg OD Tablet Without Water n=39 Participants Single oral administration of 1 tolvaptan 15 mg OD tablet without water under fasting conditions	Cohort 1: 15 mg OD Tablet With Water n=39 Participants Single oral administration of 1 tolvaptan 15 mg OD tablet with water under fasting conditions	Cohort 2: 30 mg Conventional Tablet n=41 Participants Single oral administration of 1 tolvaptan 30 mg conventional tablet with water under fasting conditions	Cohort 2: 30 mg OD Tablet Without Water n=41 Participants Single oral administration of 1 tolvaptan 30 mg OD tablet without water under fasting conditions	Cohort 2: 30 mg OD Tablet With Water n=41 Participants Single oral administration of 1 tolvaptan 30 mg OD tablet with water under fasting conditions
Maximum Plasma Concentration (Cmax) of Tolvaptan	131 ng/mL Standard Deviation 71.0	149 ng/mL Standard Deviation 72.6	125 ng/mL Standard Deviation 63.1	203 ng/mL Standard Deviation 72.7	218 ng/mL Standard Deviation 56.0	198 ng/mL Standard Deviation 54.7

PRIMARY outcome

Timeframe: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours post-dose

Population: Bioequivalence analysis set: all subjects with both AUCt and Cmax values across Period 1, Period 2, and Period 3.