A Phase 2, Multi-center, Open-label, Dose-finding Trial to Investigate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of OPC-41061 in Patients With Chronic Renal Failure Undergoing Hemodialysis or Hemodiafiltration

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01876381
• Collaborator: (none)
• Enrollment: 26
• Locations: 5
• Arm: 1
• Duration (Months): 8
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

To investigate the safety, pharmacokinetics, pharmacodynamics, and efficacy of OPC-41061 in patients with chronic renal failure undergoing hemodialysis or hemodiafiltration using variables, such as daily urine volume and increase in interval body weights between hemodialysis or hemodiafiltration, in 4-day intermittant administration (excluding the days of hemodialysis or hemodiafiltration) at the dose fixed during the dose-escalation period

Condition or Disease	Intervention/Treatment	Phase
Chronic Renal Failure	Drug: OPC-41061	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multi-center, Open-label, Dose-finding Trial to Investigate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of OPC-41061 in Patients With Chronic Renal Failure Undergoing Hemodialysis or Hemodiafiltration
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OPC-41061	Drug: OPC-41061; The maximum number of days of administration will be 8 days (8 doses) in total 4 days each in the dose-escalation period and intermittant administration period. The investigational medicinal product (IMP) will be administered once daily after breakfast

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Daily Urine Volume [Baseline and Day 14 (Intermittent Administration Period)]

   The daily urine volume at each timepoint and its change and the percent change from baseline will be summarized with descriptive statistics (number, mean, standard deviation [SD], minimum, median, maximum [same for following parameters]).

Secondary Outcome Measures

1. Change From Baseline in Total Fluid Removal Per Week by Dialysis [Baseline (pretreatment observation period) and Intermittent Administration Period (Day 10 to Day 15)]

   The total volume of fluid removed per week by dialysis at each timepoint and its change from baseline will be summarized with descriptive statistics.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with chronic renal failure who are undergoing hemodialysis or hemodiafiltration three times a week

• Subjects between the ages of 20 and 80, inclusive (at time of informed consent)

• Subjects who are inpatients or who can be admitted to the trial site for the duration of the trial period

• Subjects who, together with their partner, are able to practice one of the specified contraceptive methods until 4 weeks after the final trial drug administration

• Patients who are capable of providing written informed consent themselves before any trial-related procedures are performed

Exclusion Criteria:

• Subjects with a complication of urinary impairment due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause

• Subject with daily urine volume less than 500 mL

• Subject with Cardiac function of NYHA class 4

• Subjects with serious ischemic heart disease, who are judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial

• Subjects with serious arrhythmia, who are judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial

• Subjects who are concomitantly undergoing peritoneal dialysis

• Subjects with ascites due to cirrhosis or cancer, requring medical treatments

• Subjects with any of the following medical histories:

• History of cerebrovascular disorder or coronary artery disease within 4 weeks prior to informed consent

• History of hypersensitivity or idiosyncratic reaction to benzazepine derivatives such as mozavaptan hydrochloride or benazepril hydrochloride

• Subjects with any of the following abnormal laboratory values:

• Hemoglobin lower than 8.0 g/dL, total bilirubin higher than 3.0 mg/dL, ALT (GPT) or AST (GOT) 2 times the upper limit of the reference range of the trial site, serum sodium higher than the upper limit of the reference range of the trial site, serum sodium lower than 125mEq/L

• Subjects with serum potassium higher than 6.0mEq/L and abnormal findings inappropriate for inclusion in the trial are observed by 12-lead ECG

• Subjects who are unable to sense thirst or who have difficulty with fluid or food intake

• Subjects who have participated in any other clinical trial or post-marketing clinical studies within 4 weeks prior to informed consent

• Female subjects who are pregnant, possibly pregnant, or nursing, or who plan to become pregnant during the trial period

• Subjects otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chube Region		Japan
2		Kanto Region		Japan
3		Kinki Region		Japan
4		Kyushu Region		Japan
5		Tohoku Region		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Chair: Kyoji Imaoka, Mr, Otsuka Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01876381
• Other Study ID Numbers: 156-12-007; JapicCTI-132147
• First Posted: Jun 12, 2013
• Last Update Posted: Aug 24, 2018
• Last Verified: Nov 1, 2017

• Additional relevant MeSH terms: Renal Insufficiency; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Tolvaptan

Study Results

Participant Flow

Arm/Group Title	OPC-41061
Arm/Group Description	Dose-titration period Administration of OPC-41061 will be started at 7.5 mg/day and the dose was increased stepwise up to as high as 60 mg/day until the dose for intermittent administration is determined. (If the dose was not fixed, the subject received the next higher dose following a 6-day washout period.) Intermittent administration period Subjects received once-daily 4-day intermittent administration of OPC-41061 (days on which hemodialysis or hemodiafiltration was not performed).
Period Title: Overall Study
STARTED	23
COMPLETED	16
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	OPC-41061
Arm/Group Description	Dose-titration period Administration of OPC-41061 will be started at 7.5 mg/day and the dose was increased stepwise up to as high as 60 mg/day until the dose for intermittent administration is determined. (If the dose was not fixed, the subject received the next higher dose following a 6-day washout period.) Intermittent administration period Subjects received once-daily 4-day intermittent administration of OPC-41061 (days on which hemodialysis or hemodiafiltration was not performed).
Overall Participants	23
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 47.8%
>=65 years	12 52.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.4 (12.5)
Sex: Female, Male (Count of Participants)
Female	8 34.8%
Male	15 65.2%
Region of Enrollment (participants) [Number]
Japan	23 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Daily Urine Volume
Description	The daily urine volume at each timepoint and its change and the percent change from baseline will be summarized with descriptive statistics (number, mean, standard deviation [SD], minimum, median, maximum [same for following parameters]).
Time Frame	Baseline and Day 14 (Intermittent Administration Period)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	OPC-41061
Arm/Group Description	Dose-titration period Administration of OPC-41061 will be started at 7.5 mg/day and the dose was increased stepwise up to as high as 60 mg/day until the dose for intermittent administration is determined. (If the dose was not fixed, the subject received the next higher dose following a 6-day washout period.) Intermittent administration period Subjects received once-daily 4-day intermittent administration of OPC-41061 (days on which hemodialysis or hemodiafiltration was not performed).
Measure Participants	16
Mean (Standard Deviation) [ml]	481.0 (427.1)

2. Secondary Outcome

Title	Change From Baseline in Total Fluid Removal Per Week by Dialysis
Description	The total volume of fluid removed per week by dialysis at each timepoint and its change from baseline will be summarized with descriptive statistics.
Time Frame	Baseline (pretreatment observation period) and Intermittent Administration Period (Day 10 to Day 15)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	OPC-41061
Arm/Group Description	Dose-titration period Administration of OPC-41061 will be started at 7.5 mg/day and the dose was increased stepwise up to as high as 60 mg/day until the dose for intermittent administration is determined. (If the dose was not fixed, the subject received the next higher dose following a 6-day washout period.) Intermittent administration period Subjects received once-daily 4-day intermittent administration of OPC-41061 (days on which hemodialysis or hemodiafiltration was not performed).
Measure Participants	16
Mean (Standard Deviation) [ml]	-1425.0 (2139.7)

Adverse Events

Time Frame	From the start date of IMP administration to date of the final examination (up to Intermittent Administration Period Day15)
Arm/Group Title	OPC-41061
Arm/Group Description	Dose-titration period Administration of OPC-41061 will be started at 7.5 mg/day and the dose was increased stepwise up to as high as 60 mg/day until the dose for intermittent administration is determined. (If the dose was not fixed, the subject received the next higher dose following a 6-day washout period.) Intermittent administration period Subjects received once-daily 4-day intermittent administration of OPC-41061 (days on which hemodialysis or hemodiafiltration was not performed).
All Cause Mortality
	OPC-41061
	Affected / at Risk (%)	# Events
Total	0/23 (0%)
Serious Adverse Events
	OPC-41061
	Affected / at Risk (%)	# Events
Total	0/23 (0%)
Other (Not Including Serious) Adverse Events
	OPC-41061
	Affected / at Risk (%)	# Events
Total	13/23 (56.5%)
General disorders
Thirst	3/23 (13%)
Malaise	2/23 (8.7%)
Injection site erosion	1/23 (4.3%)
Pyrexia	1/23 (4.3%)
Vessel puncture site pain	1/23 (4.3%)
Vessel puncture site pruritus	1/23 (4.3%)
Infections and infestations
Nasopharyngitis	2/23 (8.7%)
Periodontitis	1/23 (4.3%)
Urinary tract infection	1/23 (4.3%)
Oral herpes	1/23 (4.3%)
Injury, poisoning and procedural complications
Shunt stenosis	2/23 (8.7%)
Excoriation	1/23 (4.3%)
Procedural hypotension	1/23 (4.3%)
Investigations
Blood pressure increased	1/23 (4.3%)
Blood urine present	1/23 (4.3%)
Metabolism and nutrition disorders
Hyperkalaemia	2/23 (8.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/23 (8.7%)
Back pain	1/23 (4.3%)
Limb discomfort	1/23 (4.3%)
Renal and urinary disorders
Pollakiuria	2/23 (8.7%)
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic	1/23 (4.3%)
Skin and subcutaneous tissue disorders
Rash	1/23 (4.3%)
Vascular disorders
Hypotension	1/23 (4.3%)

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.