Trial Outcomes & Findings for Phase I Study of OPC-61815 (NCT NCT03510663)

Last Updated: 2021-05-10

Results Overview

For each OPC-61815 dose, the upper limit of the confidence interval (CI) for the time-matched difference in the least squares (LS) mean for the change in QT corrected for heart rate by Fridericia's formula (QTcF) from baseline compared to the placebo data was evaluated to determine if it was lower than 10 msec at all postdose time points. Using a linear mixed effect model with baseline QTcF in each treatment period as a covariate, treatment, sequence, treatment period, time point, and interaction between treatment and time point as fixed effects, and subject as a random effect, point estimates and CIs for the time-matched difference in the LS mean for the change in QTcF from baseline compared to the placebo data were calculated.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

48 participants

Primary outcome timeframe

Baseline, 1h, 1.5h, 2h, 3h, 4h, 6h, 12h, 24h after dosing

Results posted on

2021-05-10

Participant Flow

Participant milestones

Participant milestones
Measure	Sequence 1 (ABDC) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of investigational medicinal product (IMP) administration in a treatment period and the next treatment period.	Sequence 2 (DACB) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 3 (BCAD) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 4 (CDBA) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 5 (ABCD) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 6 (CADB) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 7 (BDAC) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 8 (DCBA) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.
Overall Study STARTED	6	6	6	6	6	6	6	6
Overall Study COMPLETED	6	5	6	6	6	6	6	6
Overall Study NOT COMPLETED	0	1	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1 (ABDC) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of investigational medicinal product (IMP) administration in a treatment period and the next treatment period.	Sequence 2 (DACB) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 3 (BCAD) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 4 (CDBA) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 5 (ABCD) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 6 (CADB) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 7 (BDAC) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 8 (DCBA) Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.
Overall Study Withdrawal by Subject	0	1	0	0	0	0	0	0

Baseline Characteristics

Phase I Study of OPC-61815

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence 1 (ABDC) n=6 Participants Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of investigational medicinal product (IMP) administration in a treatment period and the next treatment period.	Sequence 2 (DACB) n=6 Participants Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 3 (BCAD) n=6 Participants Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 4 (CDBA) n=6 Participants Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 5 (ABCD) n=6 Participants Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 6 (CADB) n=6 Participants Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 7 (BDAC) n=6 Participants Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Sequence 8 (DCBA) n=6 Participants Each subject received a single dose of each of the following 4 study treatments in Periods 1 to 4 in the assigned sequence. A: OPC-6181 16 mg B: OPC-61815 32 mg C: placebo D: moxifloxacin OPC-61815 and placebo were intravenously administered in a double-blind fashion, and a moxifloxacin 400 mg tablet was orally administered with water in an open-label fashion. A washout period of at least 6 days was set between the days of IMP administration in a treatment period and the next treatment period.	Total n=48 Participants Total of all reporting groups
Age, Continuous	31.7 years STANDARD_DEVIATION 11.4 • n=39 Participants	27.3 years STANDARD_DEVIATION 7.4 • n=41 Participants	30.2 years STANDARD_DEVIATION 7.7 • n=35 Participants	26.5 years STANDARD_DEVIATION 9.1 • n=31 Participants	28.3 years STANDARD_DEVIATION 8.4 • n=146 Participants	30.3 years STANDARD_DEVIATION 4.4 • n=19 Participants	27.5 years STANDARD_DEVIATION 4.1 • n=147 Participants	26.2 years STANDARD_DEVIATION 6.4 • n=193 Participants	28.5 years STANDARD_DEVIATION 7.3
Sex: Female, Male Female	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	0 Participants n=146 Participants	0 Participants n=19 Participants	0 Participants n=147 Participants	0 Participants n=193 Participants	0 Participants
Sex: Female, Male Male	6 Participants n=39 Participants	6 Participants n=41 Participants	6 Participants n=35 Participants	6 Participants n=31 Participants	6 Participants n=146 Participants	6 Participants n=19 Participants	6 Participants n=147 Participants	6 Participants n=193 Participants	48 Participants
Race/Ethnicity, Customized Japanese	6 Participants n=39 Participants	6 Participants n=41 Participants	6 Participants n=35 Participants	6 Participants n=31 Participants	6 Participants n=146 Participants	6 Participants n=19 Participants	6 Participants n=147 Participants	6 Participants n=193 Participants	48 Participants
Region of Enrollment Japan	6 Participants n=39 Participants	6 Participants n=41 Participants	6 Participants n=35 Participants	6 Participants n=31 Participants	6 Participants n=146 Participants	6 Participants n=19 Participants	6 Participants n=147 Participants	6 Participants n=193 Participants	48 Participants

PRIMARY outcome

Timeframe: Baseline, 1h, 1.5h, 2h, 3h, 4h, 6h, 12h, 24h after dosing

Population: Central tendency analysis for OPC-61815 was performed for subjects in the Pharmacodynamic Analysis Set who appropriately completed all IMP treatments and for whom predose and postdose QT data are available for all 4 treatment periods. One subject was excluded from the central tendency analysis due to lack of QT data following OPC-61815 16 mg, OPC-61815 32 mg, and placebo administration.

Outcome measures

Outcome measures
Measure	OPC-61815 16 mg n=48 Participants OPC-61815 16 mg was intravenously administered once a week.	OPC-61815 32 mg n=48 Participants OPC-61815 32 mg was intravenously administered once a week.	Moxifloxacin n=48 Participants 400 mg tablet was orally administrated once a week.	Placebo n=48 Participants Placebo was intravenously administered once a week.
Time-matched Difference Between the OPC-61815/Moxifloxacin and Placebo Data in Change From Baseline for QTcF in 12-lead Holter Electrocardiogram (ECG) 1.5 hours postdose	2.0 msec Standard Error 1.1	1.3 msec Standard Error 1.1	9.5 msec Standard Error 1.1	-0.7 msec Standard Error 1.1
Time-matched Difference Between the OPC-61815/Moxifloxacin and Placebo Data in Change From Baseline for QTcF in 12-lead Holter Electrocardiogram (ECG) 1 hour postdose	0.9 msec Standard Error 1.1	0.0 msec Standard Error 1.1	9.9 msec Standard Error 1.1	-0.9 msec Standard Error 1.1
Time-matched Difference Between the OPC-61815/Moxifloxacin and Placebo Data in Change From Baseline for QTcF in 12-lead Holter Electrocardiogram (ECG) 2 hours postdose	1.7 msec Standard Error 1.1	0.4 msec Standard Error 1.1	10.8 msec Standard Error 1.1	-0.4 msec Standard Error 1.1
Time-matched Difference Between the OPC-61815/Moxifloxacin and Placebo Data in Change From Baseline for QTcF in 12-lead Holter Electrocardiogram (ECG) 3 hours postdose	-1.2 msec Standard Error 1.1	-2.2 msec Standard Error 1.1	10.9 msec Standard Error 1.1	-0.6 msec Standard Error 1.1
Time-matched Difference Between the OPC-61815/Moxifloxacin and Placebo Data in Change From Baseline for QTcF in 12-lead Holter Electrocardiogram (ECG) 4 hours postdose	-2.6 msec Standard Error 1.1	-2.2 msec Standard Error 1.1	11.1 msec Standard Error 1.1	1.5 msec Standard Error 1.1
Time-matched Difference Between the OPC-61815/Moxifloxacin and Placebo Data in Change From Baseline for QTcF in 12-lead Holter Electrocardiogram (ECG) 6 hours postdose	-11.9 msec Standard Error 1.1	-10.8 msec Standard Error 1.1	1.9 msec Standard Error 1.1	-8.5 msec Standard Error 1.1
Time-matched Difference Between the OPC-61815/Moxifloxacin and Placebo Data in Change From Baseline for QTcF in 12-lead Holter Electrocardiogram (ECG) 12 hours postdose	-9.6 msec Standard Error 1.1	-9.8 msec Standard Error 1.1	2.6 msec Standard Error 1.1	-4.7 msec Standard Error 1.1
Time-matched Difference Between the OPC-61815/Moxifloxacin and Placebo Data in Change From Baseline for QTcF in 12-lead Holter Electrocardiogram (ECG) 24 hours postdose	-3.6 msec Standard Error 1.1	-2.8 msec Standard Error 1.1	4.3 msec Standard Error 1.1	-2.7 msec Standard Error 1.1

Adverse Events

OPC-61815 16 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

OPC-61815 32 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Moxifloxacin

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	OPC-61815 16 mg n=47 participants at risk OPC-61815 16 mg was intravenously administered once a week.	OPC-61815 32 mg n=47 participants at risk OPC-61815 32 mg was intravenously administered once a week.	Moxifloxacin n=48 participants at risk 400 mg tablet was orally administrated once a week.	Placebo n=47 participants at risk Placebo was intravenously administered once a week.
General disorders Vessel puncture site pain	0.00% 0/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	2.1% 1/48 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.
Infections and infestations Folliculitis	0.00% 0/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/48 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	2.1% 1/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.
Infections and infestations Nasopharyngitis	2.1% 1/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	2.1% 1/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/48 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.
Infections and infestations Pharyngitis	0.00% 0/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/48 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	2.1% 1/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.
Infections and infestations Tonsillitis	2.1% 1/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	2.1% 1/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/48 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.
Skin and subcutaneous tissue disorders Pruritus	2.1% 1/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	8.5% 4/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/48 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.	0.00% 0/47 • Treatment-emergent adverse events were collected from the start of IMP administration up to an average of 31 days Safety Analysis Set included subjects who received at least 1 dose of IMP and had postdose safety data.

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place