Trial Outcomes & Findings for Efficacy and Safety Trial of OPC-61815 Injection Compared With Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure (NCT NCT03772041)

NCT ID: NCT03772041

Last Updated: 2021-08-05

Results Overview

Change in body weight from baseline (before investigational medicinal product \[IMP\] administration on Day 1) at time of final IMP administration (day after final IMP administration). A negative change from baseline indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

294 participants

Primary outcome timeframe

Baseline, Day 6

Results posted on

2021-08-05

Participant Flow

Participant milestones

Participant milestones
Measure	OPC-61815 Injection 16 mg Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.	Tolvaptan Tablet 15mg Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
Overall Study STARTED	149	145
Overall Study COMPLETED	135	135
Overall Study NOT COMPLETED	14	10

Reasons for withdrawal

Reasons for withdrawal
Measure	OPC-61815 Injection 16 mg Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.	Tolvaptan Tablet 15mg Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
Overall Study Adverse Event	8	3
Overall Study Withdrawal by Subject	0	2
Overall Study Protocol Violation	4	2
Overall Study Physician Decision	2	3

Baseline Characteristics

Efficacy and Safety Trial of OPC-61815 Injection Compared With Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OPC-61815 Injection 16 mg n=149 Participants Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.	Tolvaptan Tablet 15mg n=145 Participants Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.	Total n=294 Participants Total of all reporting groups
Age, Continuous	74.0 years STANDARD_DEVIATION 10.2 • n=5 Participants	75.4 years STANDARD_DEVIATION 8.2 • n=7 Participants	74.7 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	47 Participants n=7 Participants	84 Participants n=5 Participants
Sex: Female, Male Male	112 Participants n=5 Participants	98 Participants n=7 Participants	210 Participants n=5 Participants
Race/Ethnicity, Customized Asian	149 Participants n=5 Participants	145 Participants n=7 Participants	294 Participants n=5 Participants
Region of Enrollment Japan	149 Participants n=5 Participants	145 Participants n=7 Participants	294 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 6

Population: Full Analysis Set: subjects who received at least one dose of IMP and had at least one postbaseline weight measurement

Outcome measures

Outcome measures
Measure	OPC-61815 Injection 16 mg n=149 Participants Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.	Tolvaptan Tablet 15mg n=144 Participants Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
Change From Baseline in Body Weight	-1.67 kg Interval -1.93 to -1.41	-1.36 kg Interval -1.62 to -1.1

SECONDARY outcome

Timeframe: Baseline, Day 6

Population: Full Analysis Set: subjects who received at least one dose of IMP and had at least one postbaseline weight measurement were included in the full analysis. "Number Analyzed" = number of subjects with baseline symptoms.

The improvement rate was defined as the percentage of subjects in whom the symptom was present at baseline and it markedly improved or improved after IMP administration. Improvement category is a 4-point scale below: * Markedly improved * Improved * Unchanged * Deteriorated

Outcome measures

Outcome measures
Measure	OPC-61815 Injection 16 mg n=149 Participants Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.	Tolvaptan Tablet 15mg n=145 Participants Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
Improvement Rate for Lower Limb Edema and Pulmonary Congestion Lower Limb Edema	68.9 percentage of participants	75.7 percentage of participants
Improvement Rate for Lower Limb Edema and Pulmonary Congestion Pulmonary Congestion	56.1 percentage of participants	64.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 6

Population: Subjects with baseline values in the Full Analysis Set

* Jugular Venous Distension: the presence of Jugular Venous Distension was checked, and if present, the height (in cm) from the sternal angle to the highest point of pulsation in the internal Jugular vein was measured with the subject in a semi-upright position. A negative change from baseline indicates improvement. * Hepatomegaly: the presence of a palpable liver was checked, and if present, the width (distance from the right costal arch of the right chest, in cm) was measured. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	OPC-61815 Injection 16 mg n=149 Participants Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.	Tolvaptan Tablet 15mg n=145 Participants Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
Change From Baseline in Jugular Venous Distension and Hepatomegaly Jugular Venous Distension	-2.89 cm Interval -3.45 to -2.33	-3.15 cm Interval -3.68 to -2.62
Change From Baseline in Jugular Venous Distension and Hepatomegaly Hepatomegaly	-0.93 cm Interval -1.44 to -0.43	-0.88 cm Interval -1.43 to -0.33

SECONDARY outcome

Timeframe: Baseline, Day 6

Percentage of subjects in whom the symptom was present at baseline and disappeared after IMP administration was provided. * The presence of pulmonary rales was checked by auscultation. * The presence of cardiac third sound was checked by auscultation.

Outcome measures

Outcome measures
Measure	OPC-61815 Injection 16 mg n=149 Participants Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.	Tolvaptan Tablet 15mg n=145 Participants Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
Percentage of Subjects Who Achieve Resolution of Pulmonary Rales and Third Cardiac Sound Pulmonary Rales	74.3 percentage of participants	78.9 percentage of participants
Percentage of Subjects Who Achieve Resolution of Pulmonary Rales and Third Cardiac Sound Third Cardiac Sound	31.7 percentage of participants	31.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 6

Population: Full Analysis Set: subjects who received at least one dose of IMP and had at least one postbaseline weight measurement were included in the full analysis. "Overall Number of Participants Analyzed" = number of subjects with a baseline of class II or more.

NYHA classification assesses the severity of heart failure based on subjective symptoms as follows. Class I: No limitations of physical activity. Ordinary physical activity caused no undue fatigue, palpitation, dyspnea or anginal pain. Class II: Slight limitation of physical activity, comfortable at rest. Ordinary physical activity resulted in fatigue, palpitation, dyspnea or anginal pain. Class III: Marked limitation of physical activity, comfortable at rest. Less than ordinary physical activity caused fatigue, palpitation, dyspnea or anginal pain. Class IV: Inability to carry on any physical activity without discomfort. heart failure or anginal syndrome may have been present even at rest. If any physical activity was undertaken, discomfort was increased. Of the subjects with Class II or higher at baseline, the percentage of subjects whose NYHA classification stage at the time of final IMP administration improved by 1 or more grades was provided.

Outcome measures

Outcome measures
Measure	OPC-61815 Injection 16 mg n=136 Participants Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.	Tolvaptan Tablet 15mg n=120 Participants Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
Improvement Rate for New York Heart Association (NYHA) Classification	44.9 percentage of participants	42.5 percentage of participants

Adverse Events

OPC-61815 Injection 16 mg

Serious events: 6 serious events

Other events: 61 other events

Deaths: 0 deaths

Tolvaptan Tablet 15mg

Serious events: 5 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OPC-61815 Injection 16 mg n=149 participants at risk Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.	Tolvaptan Tablet 15mg n=145 participants at risk Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
Cardiac disorders Atrial fibrillation	0.67% 1/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Cardiac disorders Cardiac failure	0.67% 1/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Cardiac disorders Cardiac failure acute	0.67% 1/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Cardiac disorders Coronary artery stenosis	0.00% 0/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.69% 1/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Cardiac disorders Sinus node dysfunction	0.00% 0/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.69% 1/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Cardiac disorders Ventricular tachycardia	0.00% 0/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.69% 1/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Gastric antral vascular ectasia	0.67% 1/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Infections and infestations Sepsis	0.67% 1/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Infections and infestations Urinary tract infection	0.00% 0/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.69% 1/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Metabolism and nutrition disorders Hyperkalaemia	0.67% 1/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Nervous system disorders General infarction	0.00% 0/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.69% 1/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.

Other adverse events

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

Measure	OPC-61815 Injection 16 mg n=149 participants at risk Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.	Tolvaptan Tablet 15mg n=145 participants at risk Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.
Blood and lymphatic system disorders Anaemia	2.0% 3/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	2.8% 4/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Cardiac disorders Atrial fibrillation	0.67% 1/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	2.1% 3/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Cardiac disorders Ventricular tachycardia	2.0% 3/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.69% 1/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Constipation	6.0% 9/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	6.2% 9/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Dry mouth	2.7% 4/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	5.5% 8/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Nausea	2.0% 3/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
General disorders Pyrexia	2.7% 4/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	1.4% 2/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
General disorders Thirst	8.7% 13/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	11.0% 16/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Investigations Blood potassium increased	2.0% 3/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.69% 1/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Metabolism and nutrition disorders Dehydration	10.1% 15/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	4.1% 6/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Metabolism and nutrition disorders Hyperkalaemia	5.4% 8/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	2.1% 3/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Metabolism and nutrition disorders Hypernatraemia	2.7% 4/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	2.1% 3/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Metabolism and nutrition disorders Hyperuricaemia	2.7% 4/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.69% 1/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Renal and urinary disorders Renal impairment	2.7% 4/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	1.4% 2/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Skin and subcutaneous tissue disorders Eczema	2.0% 3/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Skin and subcutaneous tissue disorders Rash	2.0% 3/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	2.1% 3/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.
Vascular disorders Hypotension	2.0% 3/149 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.	3.4% 5/145 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 15 days Subjects who received at least one dose of IMP were included in the safety analysis.