Trial Outcomes & Findings for Safety Trial of OPC-61815 Injection in Patients With Congestive Heart Failure Who Have Difficulty With or Are Incapable of Oral Intake (NCT NCT03962101)

Last Updated: 2021-09-05

Results Overview

"An AE is defined as any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is an AE that leads to death, is life-threatening, results in persistent or significant disability/incapacity, requires in-patient or prolonged hospitalization, results in a congenital anomaly/birth defect, or any other important medical event which is medically significant. A TEAE is an AE that occurs only after a subject has received IMP.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

45 participants

Primary outcome timeframe

From the start of IMP administration (Day 1) up to 15 days

Results posted on

2021-09-05

Participant Flow

A total of 45 subjects were administered investigational medicinal product (IMP): 38 subjects with dose maintained at 8 mg, and 7 subjects with dose increased to 16 mg. None of the subjects reduced the dose after the dose was increased to 16 mg. All 45 subjects received at least one dose of IMP and thus were included in the safety analysis set. Overall, 41 subjects completed the trial (34 of those subjects completed the trial early), and 4 subjects were discontinued from the trial.

Participant milestones

Participant milestones
Measure	OPC-61815 Injection Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8mg, increase the dose to 16mg on Day 2 or Day 3, according to the dose escalation criteria.
Overall Study STARTED	45
Overall Study COMPLETED	41
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	OPC-61815 Injection Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8mg, increase the dose to 16mg on Day 2 or Day 3, according to the dose escalation criteria.
Overall Study Adverse Event	1
Overall Study Physician Decision	2
Overall Study Not related to medical events	1

Baseline Characteristics

Safety Trial of OPC-61815 Injection in Patients With Congestive Heart Failure Who Have Difficulty With or Are Incapable of Oral Intake

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OPC-61815 Injection n=45 Participants Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8mg, increase the dose to 16mg on Day 2 or Day 3, according to the dose escalation criteria.
Age, Continuous	73.7 years STANDARD_DEVIATION 11.1 • n=93 Participants
Sex: Female, Male Female	22 Participants n=93 Participants
Sex: Female, Male Male	23 Participants n=93 Participants
Race/Ethnicity, Customized Asian	45 Participants n=93 Participants
Region of Enrollment Japan	45 Participants n=93 Participants

PRIMARY outcome

Timeframe: From the start of IMP administration (Day 1) up to 15 days

Population: Safety Analysis Set: subjects who received at least one dose of IMP

Outcome measures

Outcome measures
Measure	OPC-61815 Injection n=45 Participants Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8mg, increase the dose to 16mg on Day 2 or Day 3, according to the dose escalation criteria.
Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	77.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day after final IMP administration

Population: Subjects with both baseline and evaluation of the given parameter at the specific visit.

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

Outcome measures

Outcome measures
Measure	OPC-61815 Injection n=44 Participants Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8mg, increase the dose to 16mg on Day 2 or Day 3, according to the dose escalation criteria.
Change From Baseline in Body Weight	-3.01 kg Interval -3.79 to -2.23

SECONDARY outcome

Timeframe: Baseline, Day after final IMP administration

Population: Efficacy Analysis Set: subjects who received at least one dose of IMP and had at least one postbaseline dose efficacy measurement. "Overall Number of Participants Analyzed" = number of subjects with baseline symptoms.

The improvement rate was defined as the percentage of subjects in whom a symptom was present at baseline and then 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 n=38 Participants Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8mg, increase the dose to 16mg on Day 2 or Day 3, according to the dose escalation criteria.
Improvement Rate for Lower Limb Edema	73.7 percentage of participants Interval 56.9 to 86.6

SECONDARY outcome

Timeframe: Baseline, Day after final IMP administration

Outcome measures

Outcome measures
Measure	OPC-61815 Injection n=44 Participants Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8mg, increase the dose to 16mg on Day 2 or Day 3, according to the dose escalation criteria.
Improvement Rate for Pulmonary Congestion	81.8 percentage of participants Interval 67.3 to 91.8

Adverse Events

OPC-61815 Injection Maintained at 8 mg

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

OPC-61815 Injection Increased to 16 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OPC-61815 Injection Maintained at 8 mg n=38 participants at risk Intravenous administration of OPC-61815 at 8 mg once daily for a maximum of 5 days.	OPC-61815 Injection Increased to 16 mg n=7 participants at risk Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8 mg, increase the dose to 16 mg on Day 2 and onward, according to the dose escalation criteria.
Cardiac disorders Ventricular tachycardia	2.6% 1/38 • 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% 0/7 • 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.6% 1/38 • 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% 0/7 • 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

Other adverse events
Measure	OPC-61815 Injection Maintained at 8 mg n=38 participants at risk Intravenous administration of OPC-61815 at 8 mg once daily for a maximum of 5 days.	OPC-61815 Injection Increased to 16 mg n=7 participants at risk Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8 mg, increase the dose to 16 mg on Day 2 and onward, according to the dose escalation criteria.
Cardiac disorders Ventricular tachycardia	5.3% 2/38 • 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% 0/7 • 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	28.9% 11/38 • 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.	14.3% 1/7 • 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	5.3% 2/38 • 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% 0/7 • 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 Haematochezia	5.3% 2/38 • 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% 0/7 • 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 Injection site inflammation	5.3% 2/38 • 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% 0/7 • 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.
Hepatobiliary disorders Hepatic function abnormal	13.2% 5/38 • 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% 0/7 • 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	10.5% 4/38 • 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% 0/7 • 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 Hypokalaemia	5.3% 2/38 • 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.	28.6% 2/7 • 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.
Musculoskeletal and connective tissue disorders Back pain	5.3% 2/38 • 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% 0/7 • 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.
Psychiatric disorders Delirium	5.3% 2/38 • 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.	14.3% 1/7 • 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.
Psychiatric disorders Insomnia	10.5% 4/38 • 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% 0/7 • 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 Dry skin	5.3% 2/38 • 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% 0/7 • 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	5.3% 2/38 • 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% 0/7 • 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 Phlebitis	5.3% 2/38 • 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% 0/7 • 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.

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