A Study of OPC-41061 in Subjects With Cardiac-induced Edema (Congestive Heart Failure)

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00544869
• Collaborator: (none)
• Enrollment: 52
• Locations: 6
• Arm: 1
• Duration (Months): 16.1
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

To investigate the plasma drug level, efficacy, and safety of 7-day repeated oral administration of OPC-41061 at 15 mg/day (treatment period 1) and subsequent 7-day repeated administration of OPC-41061 at 15 mg/day or 30 mg/day if diuretic effect is insufficient (treatment period 2) in congestive heart failure (CHF) patients with extracellular volume expansion despite conventional diuretic therapy.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Edema	Drug: OPC-41061 （Tolvaptan)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 3 Open-label, Study of OPC-41061 in Subjects With Cardiac-induced Edema (Congestive Heart Failure) - an Investigation of the Safety of Treatment Beyond 7 Days and the Effect of Dose Escalation to 30 mg
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: OPC-41061 （Tolvaptan); 15-30mg/day,daily for 14days

Outcome Measures

Primary Outcome Measures

1. Body Weight [Baseline, Day 14 or at the time of final drug administration]

   The change of body weight from baseline at final observation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects with cardiac edema receiving diuretic treatment since 7 days prior to the commencement of study drug administration.

2. Subjects receiving one of the following diuretic treatments since 3 days prior to the commencement of study drug administration without changing the dose or dosing regimen (including subjects scheduled to start treatment during the run-in observation period).

• 1. A loop diuretic at a daily dosage equivalent to 40 mg or more of furosemide
• 1. Concomitant administration of a loop diuretic and a thiazide diuretic (at any doses)
• 1. Concomitant administration of a loop diuretic and an anti-aldosterone drug (at any doses)

1. CHF patients with lower limb edema, jugular venous distention, or pulmonary congestion due to extracellular volume expansion.

2. Male or female subjects between the ages of 20 and 85, inclusive (at time of informed consent)

3. Subjects able to stay at the study site from the day before the start of the run-in observation period until completion of post-treatment observation 2 (7 to 10 days after final study drug administration)

4. Subjects capable of giving informed consent to participate in the study of their own free will

Exclusion Criteria:

1. Heart failure patients with markedly fluctuating symptoms

2. Patients with an assisted circulation device

3. Patients with any of the following complications or symptoms:

• 1. Suspected decrease in circulatory blood flow ，
• 1. Hypertrophic cardiomyopathy (other than dilated phase)，
• 1. Cardiac valve disease with significant heart valve stenosis，
• 1. Hepatic coma

1. Patients who develop acute myocardial infarction within 30 days prior to the screening examination

2. Patients with a definite diagnosis of active myocarditis or amyloid cardiomyopathy

3. Subjects with any of the following complications or symptoms:

• 1. Poorly controlled diabetes melllitus，
• 1. Anuria，
• 1. Urination impaired due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause

1. Subjects with any of the following disease histories:

• 1. Sustained ventricular tachycardia or ventricular fibrillation within 30 days prior to the screening examination in subjects without an implanted defibrillator，
• 1. Cerebrovascular disorder within 6 months prior to the screening examination (other than asymptomatic cerebral infarction)，
• 1. A history of hypersensitivity or idiosyncratic reaction to benzazepine derivatives such as mozavaptan hydrochloride or benazepril hydrochloride.

1. Subjects who are severely obese [body mass index (BMI, body weight (kg)/height (m)2] exceeding 35]

2. Subjects with systolic blood pressure in the decubitus position exceeding 90 mmHg

3. Subjects with any of the following abnormal laboratory values:

• 1. Total bilirubin > 3.0 mg/dL,
• 1. serum creatinine > 3.0 mg/dL,
• 1. serum sodium > 147 mEq/L,
• 1. serum potassium > 5.5 mEq/L

1. Patients who are unable to take oral medication

2. Female subjects who are pregnant, possibly pregnant, or lactating, or who plan to become pregnant during the study period

3. Subjects who received any investigational drug other than OPC-41061 within 30 days prior to the screening examination

4. Subjects otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chubu region		Japan
2		Hokkaido region		Japan
3		Kanto region		Japan
4		Kinki region		Japan
5		Kyuush		Japan
6		Shikoku region		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Katsuhisa Saito, Division of New Product Evaluation and Development

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT00544869
• Other Study ID Numbers: 156-06-006
• First Posted: Oct 16, 2007
• Last Update Posted: Jan 30, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by Otsuka Pharmaceutical Co., Ltd.: Vasopressin antagonist , Cardiac Edema ,Diuretics
• Additional relevant MeSH terms: Heart Failure; Edema, Cardiac; Edema; Tolvaptan

Study Results

Participant Flow

Arm/Group Title	Stopped at End of Treatment Period 1	Continued at 15 mg/Day	Dose Escalated to 30 mg/Day
Arm/Group Description	Administration of OPC-41061 at 15 mg/day (treatment period 1) for 7 days	Subsequent 7-day repeated administration of OPC-41061 at 15 mg/day (treatment period 2)	Subsequent 7-day repeated administration of OPC-41061 at 30 mg/day (treatment period 2)
Period Title: Overall Study
STARTED	36	14	2
COMPLETED	24	12	2
NOT COMPLETED	12	2	0

Baseline Characteristics

Arm/Group Title	Stopped at End of Treatment Period 1	Continued at 15 mg/Day	Dose Escalated to 30 mg/Day	Total
Arm/Group Description	Administration of OPC-41061 at 15 mg/day (treatment period 1) for 7 days	Subsequent 7-day repeated administration of OPC-41061 at 15 mg/day (treatment period 2)	Subsequent 7-day repeated administration of OPC-41061 at 30 mg/day (treatment period 2)	Total of all reporting groups
Overall Participants	36	13	2	51
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	7 19.4%	4 30.8%	0 0%	11 21.6%
>=65 years	29 80.6%	9 69.2%	2 100%	40 78.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.3 (9.5)	67.2 (12.7)	78.5 (2.1)	70.5 (10.4)
Sex: Female, Male (Count of Participants)
Female	11 30.6%	2 15.4%	1 50%	14 27.5%
Male	25 69.4%	11 84.6%	1 50%	37 72.5%
Region of Enrollment (participants) [Number]
Japan	36 100%	13 100%	2 100%	51 100%

Outcome Measures

1. Primary Outcome

Title	Body Weight
Description	The change of body weight from baseline at final observation
Time Frame	Baseline, Day 14 or at the time of final drug administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stopped at End of Treatment Period 1	Continued at 15 mg/Day	Dose Escalated to 30 mg/Day
Arm/Group Description
Measure Participants	36	13	2
Mean (Standard Deviation) [Kg]	-2.05 (1.86)	-1.31 (2.95)	-2.9 (2.69)

Adverse Events

Time Frame	7 Days for stopped at end of treated period 1 group 14 Days for continued at 15 or 30 mg/day group
Arm/Group Title	Stopped at End of Treatment Period 1		Continued at 15 mg/Day		Dose Escalated to 30 mg/Day
Arm/Group Description	Administration of OPC-41061 at 15 mg/day (treatment period 1) for 7 days		Subsequent 7-day repeated administration of OPC-41061 at 15 mg/day (treatment period 2)		Subsequent 7-day repeated administration of OPC-41061 at 30 mg/day (treatment period 2)
All Cause Mortality
	Stopped at End of Treatment Period 1		Continued at 15 mg/Day		Dose Escalated to 30 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Stopped at End of Treatment Period 1		Continued at 15 mg/Day		Dose Escalated to 30 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/36 (8.3%)		1/13 (7.7%)		0/2 (0%)
Cardiac disorders
Cardiac Failure	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Intracardiac Thrombus	1/36 (2.8%)	1	0/13 (0%)	0	0/2 (0%)	0
Nervous system disorders
Cerebral Artery Embolism	1/36 (2.8%)	1	0/13 (0%)	0	0/2 (0%)	0
Renal and urinary disorders
Renal Failure Chronic	1/36 (2.8%)	1	0/13 (0%)	0	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Stopped at End of Treatment Period 1		Continued at 15 mg/Day		Dose Escalated to 30 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/36 (83.3%)		12/13 (92.3%)		2/2 (100%)
Blood and lymphatic system disorders
Anaemia	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Cardiac disorders
Cardiac Failure	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Ventricular Extrasystoles	0/36 (0%)	0	2/13 (15.4%)	2	0/2 (0%)	0
Ventricular Tachycardia	4/36 (11.1%)	4	0/13 (0%)	0	1/2 (50%)	1
Gastrointestinal disorders
Abdominal Pain	1/36 (2.8%)	1	1/13 (7.7%)	2	0/2 (0%)	0
Constipation	5/36 (13.9%)	5	0/13 (0%)	0	0/2 (0%)	0
Diarrhoea	1/36 (2.8%)	1	2/13 (15.4%)	2	0/2 (0%)	0
General disorders
Chest Pain	2/36 (5.6%)	2	0/13 (0%)	0	0/2 (0%)	0
Pain	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Thirst	14/36 (38.9%)	14	6/13 (46.2%)	6	0/2 (0%)	0
Infections and infestations
Nasopharyngitis	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Urinary Tract Infection	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Investigations
Alanine Aminotransferase Increased	3/36 (8.3%)	3	0/13 (0%)	0	0/2 (0%)	0
Aspartate Aminotransferase Increased	3/36 (8.3%)	3	1/13 (7.7%)	1	0/2 (0%)	0
Blood Alkaline Phosphatase Increased	0/36 (0%)	0	0/13 (0%)	0	1/2 (50%)	1
Blood Creatinine Increased	4/36 (11.1%)	4	4/13 (30.8%)	4	1/2 (50%)	1
Blood Glucose Increased	4/36 (11.1%)	4	4/13 (30.8%)	4	0/2 (0%)	0
Blood Lactate Dehydrogenase Increased	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Blood Potassium Increased	3/36 (8.3%)	3	3/13 (23.1%)	3	0/2 (0%)	0
Blood Urea Increased	6/36 (16.7%)	6	4/13 (30.8%)	4	1/2 (50%)	1
Blood Uric Acid Increased	6/36 (16.7%)	6	4/13 (30.8%)	5	1/2 (50%)	1
Blood Urine Present	1/36 (2.8%)	1	1/13 (7.7%)	1	0/2 (0%)	0
Glucose Urine Present	1/36 (2.8%)	1	1/13 (7.7%)	1	0/2 (0%)	0
White Blood Cell Count Increased	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Metabolism and nutrition disorders
Hyperkalaemia	1/36 (2.8%)	1	1/13 (7.7%)	1	0/2 (0%)	0
Hyperlipidaemia	0/36 (0%)	0	0/13 (0%)	0	1/2 (50%)	1
Hyponatraemia	1/36 (2.8%)	1	2/13 (15.4%)	2	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Psychiatric disorders
Insomnia	0/36 (0%)	0	2/13 (15.4%)	2	0/2 (0%)	0
Renal and urinary disorders
Pollakiuria	2/36 (5.6%)	2	1/13 (7.7%)	1	0/2 (0%)	0
Renal Impairment	1/36 (2.8%)	1	1/13 (7.7%)	1	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/36 (2.8%)	1	3/13 (23.1%)	3	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Decubitus Ulcer	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Haemorrhage Subcutaneous	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0
Pruritus	2/36 (5.6%)	2	1/13 (7.7%)	1	0/2 (0%)	0
Purpura	0/36 (0%)	0	1/13 (7.7%)	1	0/2 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.