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Effects of Tolvaptan vs Fluid Restriction in Hospitalized Subjects With Dilutional Hyponatremia (SALACIA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01227512
Recruitment Status : Terminated (Recruitment challenges and results of interim futility analysis, which showed less than likely to achieve primary endpoint goal-length of hospital stay.)
First Posted : October 25, 2010
Results First Posted : October 17, 2014
Last Update Posted : October 30, 2014
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Conditions Hyponatremia
Dilutional Hyponatremia
Inappropriate ADH Syndrome
Interventions Drug: tolvaptan
Other: Fluid Restriction
Enrollment 124
Recruitment Details A total of 191 participants were recruited at 81 study sites in the United States (US). A total of 124 participants were randomised to treatment.
Pre-assignment Details Participants randomized 1:1 to tolvaptan (15 mg/day,titrated to 30 mg/day or 60 mg/day) without fluid restriction or placebo with titrated fluid restriction (500 to 1500 mL/day). Stratified based on severity of baseline symptoms (3-4, or 5-6 on the Clinical Global Impression of Severity and study center. All partipants were blinded to treatment.
Arm/Group Title Tolvaptan 15-60 mg/Day Placebo
Hide Arm/Group Description Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response. Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may be titrated based on serum sodium response.
Period Title: Overall Study
Started 66 58
Completed 53 48
Not Completed 13 10
Reason Not Completed
Physician Decision             6             6
Adverse Event             4             3
Withdrawal by Subject             3             0
Participant met withdrawal criteria             0             1
Arm/Group Title Tolvaptan 15-60 mg/Day Placebo Total
Hide Arm/Group Description Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response. Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may be titrated based on serum sodium response. Total of all reporting groups
Overall Number of Baseline Participants 66 58 124
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 66 participants 58 participants 124 participants
65.7  (15.8) 67.7  (15.6) 66.7  (15.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 58 participants 124 participants
Female
29
  43.9%
34
  58.6%
63
  50.8%
Male
37
  56.1%
24
  41.4%
61
  49.2%
1.Primary Outcome
Title Length of Hospital Stay (LoS)
Hide Description LoS was time to clinically ready to be hospital discharged (CRBD) from study treatment initiation, disregarding prolonged hospitalization due solely to social factors.
Time Frame 45 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the modified intent-to-treat population (MITT) which included all randomized participants who received at least one dose of study drug regardless of any protocol violation.
Arm/Group Title Tolvaptan 15-60mg/Day Placebo
Hide Arm/Group Description:
Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response.
Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may be titrated based on serum sodium response.
Overall Number of Participants Analyzed 66 55
Median (95% Confidence Interval)
Unit of Measure: Days
3.5
(3.0 to 4.5)
4.0
(3.5 to 5.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tolvaptan 15-60mg/Day, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9495
Comments The alpha level was set at 0.05
Method Generalized Wilcoxon Test
Comments Participants who used rescue therapy within first 7 days of treatment period were censored at time they started the rescue therapy.
2.Secondary Outcome
Title Change From Baseline to 48 Hour Post Dose in Clinical Global Impression-Severity (CGI-S) of Hyponatremia Symptoms.
Hide Description

Change from baseline in blinded rater assessed CGI-S at 48 hours post-first dose or at discharge/rescue therapy, if earlier was assessed.

The CGI-S is a one-question rating scale which was as follows: "Considering your total clinical experience with hyponatremia symptoms in this particular population, how symptomatic is the patient at this time?" 0=not assessed; 1=normal, not at all symtpmatic; 2=borderline symptomatic; 3=mildly symptomatic; 4=moderately symptomatic; 5=markedly symptomatic; 6=severely symptomatic; 7=among the most severly symptomatic patients.

Time Frame Baseline to 48 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description

Analysis was performed on the modified intent-to-treat population (MITT) which included all randomized participants who received at least one dose of study drug regardless of any protocol violation.

Data were missing for one participant in the Tolvaptan group.

Arm/Group Title Tolvaptan 15-60mg/Day Placebo
Hide Arm/Group Description:
Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response.
Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction be may titrated based on serum sodium response.
Overall Number of Participants Analyzed 65 55
Median (Full Range)
Unit of Measure: Units on a scale
Baseline
4.0
(2.0 to 6.0)
4.0
(3.0 to 6.0)
48 hours post dose
2.0
(1.0 to 6.0)
3.0
(1.0 to 7.0)
Change from baseline
-1.0
(-3.0 to 3.0)
-1.0
(-3.0 to 3.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tolvaptan 15-60mg/Day, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1460
Comments alpha level was set at 0.05. p-value was derived from an ANCOVA model with treatment and clinical center as factors and baseline value as covariate.
Method ANCOVA
Comments Includes factors of treatment, study center and covariate baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.30
Confidence Interval 95%
-0.70 to 0.11
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to 24 and 72 Hours Post Dose in CGI-S of Hyponatremia Symptoms.
Hide Description

Change in CGI-S of hyponatremia symptoms from pretreatment baseline at 24 and 72 hours post-first dose, or at discharge/rescue therapy if earlier was assessed.

The CGI-S is a one-question rating scale which was as follows: "Considering your total clinical experience with hyponatremia symptoms in this particular population, how symptomatic is the patient at this time?" 0=not assessed; 1=normal, not at all symtpmatic; 2=borderline symptomatic; 3=mildly symptomatic; 4=moderately symptomatic; 5=markedly symptomatic; 6=severely symptomatic; 7=among the most severly symptomatic patients.

Time Frame Baseline to 24 and 72 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description

Analysis was performed on the modified intent-to-treat population (MITT) which included all randomized participants who received at least one dose of study drug regardless of any protocol violation.

Data were missing for one participant in the Tolvaptan group.

Arm/Group Title Tolvaptan 15-60mg/Day Placebo
Hide Arm/Group Description:
Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response.
Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may be titrated based on serum sodium response.
Overall Number of Participants Analyzed 65 55
Median (Full Range)
Unit of Measure: Units on a scale
Baseline
4.0
(2.0 to 6.0)
4.0
(3.0 to 6.0)
24 hours post-dose
3.0
(1.0 to 6.0)
3.0
(1.0 to 7.0)
Change from baseline at 24 hours
-1.0
(-3.0 to 3.0)
-1.0
(-3.0 to 2.0)
72 hours post-dose
2.0
(1.0 to 6.0)
2.0
(1.0 to 7.0)
Change from baseline at 72 hours
-2.0
(-4.0 to 3.0)
-1.0
(-4.0 to 4.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tolvaptan 15-60mg/Day, Placebo
Comments P value corresponds to 24 hours post-dose.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3150
Comments [Not Specified]
Method ANCOVA
Comments P-value was derived from an ANCOVA model with treatment and clinical center as factors and baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.19
Confidence Interval 95%
-0.57 to 0.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tolvaptan 15-60mg/Day, Placebo
Comments P value corresponds to 72 hours post-dose.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5381
Comments [Not Specified]
Method ANCOVA
Comments P-value was derived from an ANCOVA model with treatment and clinical center as factors and baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.13
Confidence Interval 95%
-0.57 to 0.30
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to 48 Hours Post Dose in Clinical Global Impression - Improvement (CGI-I) Score of Hyponatremia Symptoms.
Hide Description

Change in CGI-I score at 48 hours post-first dose or discharge/rescue therapy, if earlier was assessed.

The CGI-I is a one-question rating scale where the participant is asked to rate total improvement whether or not, in their judgment, it is due entirely to trial treatment. Compared to his/her condition at admission to the trial, how much has he/she changed? 0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse

Time Frame Baseline to 48 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the modified intent-to-treat population (MITT) which included all randomized participants who received at least one dose of study drug regardless of any protocol violation. Data were not available for 2 participants in the tolvaptan group.
Arm/Group Title Tolvaptan 15-60mg/Day Placebo
Hide Arm/Group Description:
Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response.
Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may be titrated based on serum sodium response.
Overall Number of Participants Analyzed 64 55
Median (Full Range)
Unit of Measure: Units on a scale
2.0
(1.0 to 7.0)
2.0
(1.0 to 7.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tolvaptan 15-60mg/Day, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2702
Comments P-value was derived from a Cochran-Mantel-Haenszel (CMH) row mean scores test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.26
Confidence Interval 95%
-0.73 to 0.21
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Serum Sodium Concentration (24 Hour Area Under the Curve [AUC]).
Hide Description

Average 24 hour AUC of serum sodium concentration change from baseline, from Day 1 Hour 0 up to 72 hours post-first dose was assessed.

A serum sodium sample was drawn at pre-treament and 8, 24, 48, and 72 hours post-first dose. Serum sodium was also assessed between 36 and 72 hours after the last dose.

Analysis of AUC was for daily average AUC, hence the units or AUC are mEq/L/24 hours.

Time Frame 0 to 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description

Analysis was performed on the modified intent-to-treat population (MITT) which included all randomized participants who received at least one dose of study drug regardless of any protocol violation.

Data were missing for 3 participants in the tolvaptan group and 1 participant in the placebo group.

Arm/Group Title Tolvaptan 15-60mg/Day Placebo
Hide Arm/Group Description:
Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response.
Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may titrated based on serum sodium response.
Overall Number of Participants Analyzed 63 54
Least Squares Mean (Full Range)
Unit of Measure: mEq/L
3.90
(-26.9 to 13.04)
0.13
(-20.6 to 11.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tolvaptan 15-60mg/Day, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments P-value was derived from an ANCOVA model with treatment and clinical center as factors and baseline value as covariate.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.77
Confidence Interval 95%
1.43 to 6.11
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to First 2-point Improvement in CGI-S Score.
Hide Description CGI-S data up to 72 hours were used to identify 2-point improvements. Please refer to outcome measure 2 for details on the scale. For the analysis of time to first 2-point improvement in CGI-S, CGI-S data up to Hour 72 were used to identify 2-point improvements. Data for participants who received rescue therapy were censored at the time of receiving rescue therapy. For participants who were discharged before Hour 72 without reaching 2-point improvement in CGI-S, data were censored at the time of discharge. Other participants who did not reach the 2-point improvement during the 72 hours also had their data censored at their last CGI-S observations within 72 hours.
Time Frame Up to 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the modified intent-to-treat population (MITT) which included all randomized participants who received at least one dose of study drug regardless of any protocol violation. Data were missing for 1 participant in the tolvaptan group and 3 participants in the placebo group.
Arm/Group Title Tolvaptan 15-60mg/Day Placebo
Hide Arm/Group Description:
Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response.
Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may be titrated based on serum sodium response.
Overall Number of Participants Analyzed 65 55
Median (95% Confidence Interval)
Unit of Measure: Hours
51
(49 to 72)
69
(49 to 73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tolvaptan 15-60mg/Day, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5128
Comments p-value was derived from Generalized Wilcoxon test stratified by treatment. Participants who received rescue therapy were censored at the time of receiving rescue therapy.
Method Generalized Wilcoxon Test
Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With Clinical Global Impression-Improvement (CGI-I) Score Improved to a Score of 1 or 2.
Hide Description Percentage of responders (defined as CGI-I score of 1 = very much improved or 2 = much improved) at 48 hours post-first dose, or at discharge/rescue therapy, if earlier. Participants given rescue therapy were given a score of 7.
Time Frame 48 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the modified intent-to-treat population (MITT) which included all randomized participants who received at least one dose of study drug regardless of any protocol violation. Data were missing for 2 participants in the tolvaptan group and 3 participants in the placebo group.
Arm/Group Title Tolvaptan 15-60mg/Day Placebo
Hide Arm/Group Description:
Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response.
Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may be titrated based on serum sodium response.
Overall Number of Participants Analyzed 64 55
Measure Type: Number
Unit of Measure: Percentage of participants
57.8 52.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tolvaptan 15-60mg/Day, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5795
Comments P-value was derived using a CMH test stratified by hyponatremia symptoms severity.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 1.10
Confidence Interval 95%
0.79 to 1.52
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants Requiring Rescue Therapy for Hyponatremia
Hide Description Percentage of participants requiring rescue therapy within first 7 days of treatment for hyponatremia.
Time Frame 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the modified intent-to-treat population (MITT) which included all randomized participants who received at least one dose of study drug regardless of any protocol violation. Data were missing for 3 participants in the placebo group.
Arm/Group Title Tolvaptan 15-60mg/Day Placebo
Hide Arm/Group Description:
Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response.
Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may be titrated based on serum sodium response.
Overall Number of Participants Analyzed 66 55
Measure Type: Number
Unit of Measure: Percentage of participants
3.03 9.09
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tolvaptan 15-60mg/Day, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1568
Comments p-value was derived using a CMH test stratified by hyponatremia symptoms severity.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.33
Confidence Interval 95%
0.07 to 1.65
Estimation Comments [Not Specified]
Time Frame Adverse events were recorded from the time the Informed Consent Form was signed up to 45 days after study drug administration.
Adverse Event Reporting Description The same event may appear as both an adverse event (AE) and a serious AE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Tolvaptan 15-60 mg/Day Placebo
Hide Arm/Group Description Oral tablet without fluid restriction. After the initial dose, daily dose was to be titrated to 30 mg/day or 60 mg/day based on serum sodium response. Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may be titrated based on serum sodium response.
All-Cause Mortality
Tolvaptan 15-60 mg/Day Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Tolvaptan 15-60 mg/Day Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   18/66 (27.27%)   9/55 (16.36%) 
Cardiac disorders     
Acute myocardial infarction * 1  1/66 (1.52%)  0/55 (0.00%) 
Cardiac failure acute * 1  1/66 (1.52%)  0/55 (0.00%) 
Cardiac failure * 1  1/66 (1.52%)  0/55 (0.00%) 
Right ventricular failure * 1  1/66 (1.52%)  0/55 (0.00%) 
Gastrointestinal disorders     
Diabetic gastroparesis * 1  1/66 (1.52%)  0/55 (0.00%) 
Intestinal obstruction * 1  0/66 (0.00%)  1/55 (1.82%) 
Lower gastrointestinal haemorrhage * 1  1/66 (1.52%)  0/55 (0.00%) 
Upper gastrointestinal haemorrhage * 1  0/66 (0.00%)  1/55 (1.82%) 
Hepatobiliary disorders     
Cirrhosis alcoholic * 1  1/66 (1.52%)  0/55 (0.00%) 
Hepatic failure * 1  1/66 (1.52%)  0/55 (0.00%) 
Infections and infestations     
Enterococcal infection * 1  1/66 (1.52%)  0/55 (0.00%) 
Pneumonia * 1  2/66 (3.03%)  0/55 (0.00%) 
Sepsis * 1  1/66 (1.52%)  0/55 (0.00%) 
Septic shock * 1  2/66 (3.03%)  0/55 (0.00%) 
Staphylococcal sepsis * 1  0/66 (0.00%)  1/55 (1.82%) 
Tuberculosis of central nervous system * 1  1/66 (1.52%)  0/55 (0.00%) 
Injury, poisoning and procedural complications     
Femoral neck fracture * 1  0/66 (0.00%)  1/55 (1.82%) 
Metabolism and nutrition disorders     
Hyponatraemia * 1  2/66 (3.03%)  0/55 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung cancer metastatic * 1  0/66 (0.00%)  1/55 (1.82%) 
Metastatic malignant melanoma * 1  1/66 (1.52%)  0/55 (0.00%) 
Small cell lung cancer extensive stage * 1  0/66 (0.00%)  1/55 (1.82%) 
Psychiatric disorders     
Confusional state * 1  1/66 (1.52%)  0/55 (0.00%) 
Renal and urinary disorders     
Renal failure acute * 1  3/66 (4.55%)  1/55 (1.82%) 
Respiratory, thoracic and mediastinal disorders     
Asthma * 1  1/66 (1.52%)  0/55 (0.00%) 
Respiratory failure * 1  1/66 (1.52%)  0/55 (0.00%) 
Surgical and medical procedures     
Rapid correction of hyponatraemia * 1  2/66 (3.03%)  0/55 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  0/66 (0.00%)  1/55 (1.82%) 
Hypertension * 1  0/66 (0.00%)  1/55 (1.82%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 15.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tolvaptan 15-60 mg/Day Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   52/66 (78.79%)   43/55 (78.18%) 
Gastrointestinal disorders     
Abdominal distension * 1  4/66 (6.06%)  0/55 (0.00%) 
Abdominal pain * 2  3/66 (4.55%)  3/55 (5.45%) 
Constipation * 2  10/66 (15.15%)  6/55 (10.91%) 
Diarrhoea * 2  3/66 (4.55%)  5/55 (9.09%) 
Nausea * 2  5/66 (7.58%)  3/55 (5.45%) 
General disorders     
Oedema peripheral * 2  4/66 (6.06%)  4/55 (7.27%) 
Pyrexia * 3  3/66 (4.55%)  3/55 (5.45%) 
Investigations     
Heart rate increased * 2  4/66 (6.06%)  3/55 (5.45%) 
Metabolism and nutrition disorders     
Hyperkalaemia * 2  3/66 (4.55%)  3/55 (5.45%) 
Hypokalaemia * 2  5/66 (7.58%)  4/55 (7.27%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal pain * 2  0/66 (0.00%)  3/55 (5.45%) 
Pain in extremity * 2  1/66 (1.52%)  3/55 (5.45%) 
Nervous system disorders     
Headache * 2  4/66 (6.06%)  3/55 (5.45%) 
Psychiatric disorders     
Insomnia * 2  3/66 (4.55%)  5/55 (9.09%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 2  4/66 (6.06%)  2/55 (3.64%) 
Vascular disorders     
Hypotension * 2  9/66 (13.64%)  5/55 (9.09%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 15.0
2
Term from vocabulary, MedDRA 15.1
3
Term from vocabulary, Med DRA 15.1
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Medical Affairs
Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.
Phone: 800 562-3974
Layout table for additonal information
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01227512    
Other Study ID Numbers: 156-08-275
First Submitted: October 22, 2010
First Posted: October 25, 2010
Results First Submitted: May 29, 2014
Results First Posted: October 17, 2014
Last Update Posted: October 30, 2014