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Investigation of the Superiority Effect of Orally Disintegrating Desmopressin Tablets to Placebo in Terms of Night Voids Reduction in Nocturia Adult Male Patients

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ClinicalTrials.gov Identifier: NCT01262456
Recruitment Status : Completed
First Posted : December 17, 2010
Results First Posted : October 15, 2015
Last Update Posted : October 15, 2015
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Nocturia
Interventions Drug: Desmopressin
Drug: Placebo
Enrollment 395
Recruitment Details  
Pre-assignment Details A total of 1013 participants were screened; 618 were screening failures and 395 were randomized. The most common reason for screening failure was non-fulfillment of inclusion/exclusion criteria (535 participants); 23 participants withdrew consent prior to randomization and 60 participants had other reasons for screening failure.
Arm/Group Title Placebo Double-Blind / Desmopressin 100 μg Open-Label 50 μg Double-Blind / 100 μg Open-Label Desmopressin 75 μg Double-Blind / 100 μg Open-Label
Hide Arm/Group Description Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for the 1-month open-label extension period. Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for the 1-month open-label extension period. Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for the 1-month open-label extension period.
Period Title: 3-Month Double-Blind Period
Started 143 [1] 123 [2] 129 [2]
Full Analysis Set (FAS) 142 [3] 119 [3] 124 [3]
Safety Analysis Set (SAS) 143 [4] 119 [4] 122 [4]
Completed 124 100 103
Not Completed 19 23 26
Reason Not Completed
Withdrawal by Subject             6             8             9
Lost to Follow-up             4             5             3
Adverse Event             6             4             8
Protocol Violation             3             6             6
[1]
Intent-to-Treat (ITT) population: randomized participants regardless of exposure to treatment
[2]
ITT population: randomized participants regardless of exposure to treatment
[3]
FAS: ITT with at least 1 post-treatment efficacy assessment. Analysis as randomized.
[4]
SAS: received at least 1 dose and had at least 1 safety assessment. Analysis on actual treatment.
Period Title: 1-Month Open-Label Extension Period
Started 124 100 103
Safety Analysis Set (SAS) 124 101 102 [1]
Completed 120 97 98
Not Completed 4 3 5
Reason Not Completed
Withdrawal by Subject             1             1             1
Lost to Follow-up             0             1             0
Adverse Event             2             0             2
Protocol Violation             1             0             2
Other Reason             0             1             0
[1]
1 subject was randomized to Desmopressin 75 μg but received 50 μg. Also true in Double-Blind Period
Arm/Group Title Placebo Double-Blind Desmopressin 50 μg Double-Blind Desmopressin 75 μg Double-Blind Total
Hide Arm/Group Description Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Total of all reporting groups
Overall Number of Baseline Participants 142 119 124 385
Hide Baseline Analysis Population Description
Demographic data offered from the Full Analysis Set population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 142 participants 119 participants 124 participants 385 participants
60.8  (14.2) 60.8  (13.2) 60.1  (11.6) 60.6  (13.1)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 142 participants 119 participants 124 participants 385 participants
<65 years 74 62 64 200
>=65 years 68 57 60 185
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 142 participants 119 participants 124 participants 385 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
142
 100.0%
119
 100.0%
124
 100.0%
385
 100.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 142 participants 119 participants 124 participants 385 participants
White 112 99 99 310
Black or African American 27 18 22 67
Asian 2 2 3 7
American Indian or Alaska Native 1 0 0 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 142 participants 119 participants 124 participants 385 participants
Hispanic or Latino 20 25 29 74
Not Hispanic or Latino 122 94 95 311
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 142 participants 119 participants 124 participants 385 participants
29.2  (5.25) 29.3  (4.77) 29.2  (4.79) 29.2  (4.95)
1.Primary Outcome
Title Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period
Hide Description

The number of nocturnal voids was the average over 3 consecutive 24-hour periods prior to Day 1 and prior to the during-treatment visits (Week 1, Months 1, 2, 3) as recorded in participant diaries. The first morning void was not counted as a nocturnal void. Change from baseline values for Week 1, and Months 1, 2 and 3 are reported below.

Comparison of the mean number of nocturnal voids at baseline and over a 3-month treatment period (obtained by longitudinal analysis of Week 1, and Months 1, 2 and 3) are reported in the statistical analysis. This was the first co-primary outcome. Superiority to placebo was to be simultaneously demonstrated on the 2 co-primary outcomes in a step-down approach from highest (75 μg) to lowest dose (50 μg), thereby controlling the family-wise error rate at the 5% nominal significance level.

Time Frame Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS).
Arm/Group Title Desmopressin 75 μg Double-Blind Desmopressin 50 μg Double-Blind Placebo Double-Blind
Hide Arm/Group Description:
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Overall Number of Participants Analyzed 124 119 142
Mean (Standard Deviation)
Unit of Measure: nocturnal voids
Week 1 (n=120, 116, 141) -1.06  (1.9) -0.973  (0.898) -0.591  (1.05)
Month 1 (n=117, 112, 139) -1.4  (1.01) -1.31  (1.01) -0.928  (1.96)
Month 2 (n=113, 107, 132) -1.43  (1.04) -1.4  (1.04) -1.01  (1.14)
Month 3 (n=106, 103, 125) -1.37  (1.13) -1.25  (1.01) -0.984  (1.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmopressin 75 μg Double-Blind, Placebo Double-Blind
Comments

Superiority to placebo was to be simultaneously demonstrated on the 2 co-primary outcomes in a step-down approach from highest (75 μg) to lowest dose (50 μg), thereby controlling the family-wise error rate at the 5% nominal significance level.

A summary of mean change in nocturnal voids, assessed longitudinally during 3 months of treatment, is presented below for the FAS using LOCF.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A priori threshold for significance was p<=0.05.
Method ANCOVA
Comments Repeated measures ANCOVA of change from baseline at Week 1, Months 1, 2, 3, adjusted for age (<65, ≥65 years), visit, and baseline nocturnal voids.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-0.61 to -0.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Desmopressin 50 μg Double-Blind, Placebo Double-Blind
Comments

Superiority to placebo was to be simultaneously demonstrated on the 2 co-primary outcomes in a step-down approach from highest (75 μg) to lowest dose (50 μg), thereby controlling the family-wise error rate at the 5% nominal significance level.

A summary of mean change in nocturnal voids, assessed longitudinally during 3 months of treatment, is presented below for the FAS using LOCF.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments A priori threshold for significance was p<=0.05
Method ANCOVA
Comments Repeated measures ANCOVA of change from baseline at Week 1, Months 1, 2, 3, adjusted for age (<65, ≥65 years), visit, and baseline nocturnal voids.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.57 to -0.17
Estimation Comments [Not Specified]
2.Primary Outcome
Title Adjusted Probability of Participants Achieving a >33% Reduction From Baseline in Number of Nocturnal Voids for All During-Treatment Visits up to Month 3
Hide Description

Probability of participants achieving 33% responder status during 3 months of treatment employed a longitudinal analysis assessing nocturnal void information captured in the 3-day diary. A 33% responder was defined as a participant with a decrease of at least 33% in the mean number of nocturnal voids relative to baseline. The number of nocturnal voids was the average over 3 consecutive 24-hour periods prior to Day 1 and prior to the during treatment visits (Week 1, Months 1, 2, 3) as recorded in participant diaries. The first morning void was not counted as a nocturnal void.

This was the second co-primary outcome. Superiority to placebo was to be simultaneously demonstrated on the 2 co-primary endpoints in a step-down approach from highest (75 μg) to lowest dose (50 μg), thereby controlling the family-wise error rate at the 5% nominal significance level.

Time Frame Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS).
Arm/Group Title Desmopressin 75 μg Double-Blind Desmopressin 50 μg Double-Blind Placebo Double-Blind
Hide Arm/Group Description:
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Overall Number of Participants Analyzed 124 119 142
Measure Type: Number
Unit of Measure: probability
0.67 0.67 0.50
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmopressin 75 μg Double-Blind, Placebo Double-Blind
Comments Superiority to placebo was to be simultaneously demonstrated on the 2 co-primary endpoints in a step-down approach from highest (75 μg) to lowest dose (50 μg), thereby controlling the family-wise error rate at the 5% nominal significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments A priori threshold for significance was p<=0.05.
Method Generalized Estimating Equation (GEE)
Comments GEE Method for 33% responder status at Week 1, Month 1, Month 2, and Month 3, adjusted for age (<65, ≥65 years), visit, and baseline nocturnal voids.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.04
Confidence Interval (2-Sided) 95%
1.38 to 3.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Desmopressin 50 μg Double-Blind, Placebo Double-Blind
Comments Superiority to placebo was to be simultaneously demonstrated on the 2 co-primary endpoints in a step-down approach from highest (75 μg) to lowest dose (50 μg), thereby controlling the family-wise error rate at the 5% nominal significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments A priori threshold for significance was p<=0.05.
Method Generalized Estimating Equation (GEE)
Comments GEE Method for 33% responder status at Week 1, Month 1, Month 2, and Month 3, adjusted for age (<65, ≥65 years), visit, and baseline nocturnal voids.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.98
Confidence Interval (2-Sided) 95%
1.32 to 2.96
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Mean Number of Nocturnal Voids at Month 3
Hide Description

Comparison of the mean number of nocturnal voids at baseline and at the 3-month visit. The number of nocturnal voids was the average over 3 consecutive 24-hour periods prior to the relevant visits as recorded in participant diaries. The first morning void was not counted as a nocturnal void.

The secondary efficacy outcomes (#3-7) used a hierarchical step-down approach in the order listed. The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).

Time Frame Day 1 (Baseline), Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), including participants with complete data supporting this outcome in the participant diary.
Arm/Group Title Desmopressin 75 μg Double-Blind Desmopressin 50 μg Double-Blind Placebo Double-Blind
Hide Arm/Group Description:
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Overall Number of Participants Analyzed 106 103 125
Mean (Standard Deviation)
Unit of Measure: nocturnal voids
-1.37  (1.13) -1.25  (1.01) -0.984  (1.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmopressin 75 μg Double-Blind, Placebo Double-Blind
Comments

Change from baseline in the adjusted mean number of nocturnal voids in the FAS using LOCF.

The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0029
Comments A priori threshold for significance was p<=0.05.
Method ANCOVA
Comments ANCOVA of change from baseline adjusted for age (<65, >=65) and baseline nocturnal voids using last observation carried forward.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.57 to -0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Desmopressin 50 μg Double-Blind, Placebo Double-Blind
Comments

Change from baseline in the adjusted mean number of nocturnal voids in the FAS using LOCF.

The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0128
Comments A priori threshold for significance was p<=0.05.
Method ANCOVA
Comments ANCOVA of change from baseline adjusted for age (<65, >=65) and baseline nocturnal voids.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.52 to -0.06
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Adjusted Probability of Participants Achieving a >33% Reduction From Baseline in Number of Nocturnal Voids at Month 3
Hide Description

Probability of participants achieving 33% responder status at Month 3 employed a longitudinal analysis assessing nocturnal void information captured in the 3-day diary. A 33% responder was defined as a participant with a decrease of at least 33% in the mean number of nocturnal voids relative to baseline. The number of nocturnal voids was the average over 3 consecutive 24-hour periods prior to Day 1 and prior to the Month 3 visit as recorded in participant diaries. The first morning void was not counted as a nocturnal void.

The secondary efficacy outcomes (#3-7) used a hierarchical step-down approach in the order listed. The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).

Time Frame Day 1 (Baseline), Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, including participants with complete data supporting this outcome in the participant diary.
Arm/Group Title Desmopressin 75 μg Double-Blind Desmopressin 50 μg Double-Blind Placebo Double-Blind
Hide Arm/Group Description:
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Overall Number of Participants Analyzed 106 103 125
Measure Type: Number
Unit of Measure: probability
0.68 0.66 0.54
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmopressin 75 μg Double-Blind, Placebo Double-Blind
Comments The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0233
Comments A priori threshold for significance was p<=0.05.
Method Regression, Logistic
Comments Logistical regression of 33% responder status adjusted for age (<65, >=65) and baseline nocturnal voids using last observation carried forward.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.81
Confidence Interval (2-Sided) 95%
1.08 to 3.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Desmopressin 50 μg Double-Blind, Placebo Double-Blind
Comments The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0386
Comments A priori threshold for significance was p<=0.05.
Method Regression, Logistic
Comments Logistical regression of 33% responder status adjusted for age (<65, >=65) and baseline nocturnal voids using last observation carried forward.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.72
Confidence Interval (2-Sided) 95%
1.03 to 2.87
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Mean Time to First Nocturnal Void at Month 3
Hide Description

The time to first void was defined as the time from going to bed with the intention of sleeping until first nocturnal void or until waking in the morning in the case where there was no nocturnal void. The first morning void was not counted as a nocturnal void. The time to first void was derived from the sleep and voiding diary. The mean time to first void was calculated as the average over 3 consecutive 24-hour periods prior to the Month 3 visit.

The secondary efficacy outcomes (#3-7) used a hierarchical step-down approach in the order listed. The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).

Time Frame Day 1 (Baseline), Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, including participants with complete data supporting this outcome in the participant diary.
Arm/Group Title Desmopressin 75 μg Double-Blind Desmopressin 50 μg Double-Blind Placebo Double-Blind
Hide Arm/Group Description:
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Overall Number of Participants Analyzed 106 103 125
Mean (Standard Deviation)
Unit of Measure: minutes
117  (130) 113  (119) 71.5  (108)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmopressin 75 μg Double-Blind, Placebo Double-Blind
Comments The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0026
Comments A priori threshold for significance was p<=0.05.
Method ANCOVA
Comments ANCOVA of change from baseline adjusted for age (<65, >=65) and baseline time to first nocturnal void using last observation carried forward.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 42.76
Confidence Interval (2-Sided) 95%
15.02 to 70.51
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Desmopressin 50 μg Double-Blind, Placebo Double-Blind
Comments The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0064
Comments A priori threshold for significance was p<=0.05.
Method ANCOVA
Comments ANCOVA of change from baseline adjusted for age (<65, >=65) and baseline time to first nocturnal void using last observation carried forward.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 38.95
Confidence Interval (2-Sided) 95%
11.03 to 66.88
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Nocturnal Urine Volume at Month 3
Hide Description

The nocturnal urine volume was derived from the 3-day urine volume diary. The nocturnal urine volume included the volume of the first morning void. Mean urine volumes were calculated as the average over 3 consecutive 24-hour periods prior to the Month 3 visit.

The secondary efficacy outcomes (#3-7) used a hierarchical step-down approach in the order listed. The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).

Time Frame Day 1 (Baseline), Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, including participants with complete data supporting this outcome in the participant diary.
Arm/Group Title Desmopressin 75 μg Double-Blind Desmopressin 50 μg Double-Blind Placebo Double-Blind
Hide Arm/Group Description:
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Overall Number of Participants Analyzed 103 102 124
Mean (Standard Deviation)
Unit of Measure: mL
-199  (274) -186  (263) -144  (260)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmopressin 75 μg Double-Blind, Placebo Double-Blind
Comments The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments A priori threshold for significance was p<=0.05.
Method ANCOVA
Comments ANCOVA of change from baseline adjusted for age (<65, >=65) and baseline nocturnal urine volume using last observation carried forward.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -86.17
Confidence Interval (2-Sided) 95%
-143.69 to -28.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Desmopressin 50 μg Double-Blind, Placebo Double-Blind
Comments The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0086
Comments A priori threshold for significance was p<=0.05.
Method ANCOVA
Comments ANCOVA of change from baseline adjusted for age (<65, >=65) and baseline nocturnal urine volume using last observation carried forward.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -77.80
Confidence Interval (2-Sided) 95%
-135.70 to -19.89
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in 24-Hour Urine Volume at Month 3
Hide Description

Twenty-four hour urine volume was derived from the 3-day urine volume diary. Mean urine volumes were calculated as the average over 3 consecutive 24-hour periods prior to the Month 3 visit.

The secondary efficacy outcomes (#3-7) used a hierarchical step-down approach in the order listed. The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).

Time Frame Day 1 (Baseline), Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, including participants with complete data supporting this outcome in the participant diary.
Arm/Group Title Desmopressin 75 μg Double-Blind Desmopressin 50 μg Double-Blind Placebo Double-Blind
Hide Arm/Group Description:
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Overall Number of Participants Analyzed 101 102 119
Mean (Standard Deviation)
Unit of Measure: mL
-224  (549) -194  (491) -197  (442)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmopressin 75 μg Double-Blind, Placebo Double-Blind
Comments The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4126
Comments A priori threshold for significance was p<=0.05.
Method ANCOVA
Comments ANCOVA of change from baseline adjusted for age (<65, >=65) and baseline 24-hour urine volume using last observation carried forward.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -45.31
Confidence Interval (2-Sided) 95%
-153.94 to 63.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Desmopressin 50 μg Double-Blind, Placebo Double-Blind
Comments The active treatment groups were compared to placebo using a step-down approach from highest dose (75 µg) to lowest dose (50 µg).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7353
Comments A priori threshold for significance was p<=0.05.
Method ANCOVA
Comments ANCOVA of change from baseline adjusted for age (<65, >=65) and baseline 24-hour urine volume using last observation carried forward.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -18.79
Confidence Interval (2-Sided) 95%
-127.99 to 90.41
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Period
Hide Description A TEAE was any adverse event (AE) occurring after start of treatment and within the time of residual drug effect, i.e., within 1 day for desmopressin. An adverse drug reaction (ADR) was any AE assessed by the investigator as possibly or probably related to study drug.
Time Frame From Day 1 through Month 3 (double-blind period)
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Safety analysis set (SAS)
Arm/Group Title Placebo Double-Blind Desmopressin 50 μg Double-Blind Desmopressin 75 μg Double-Blind
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Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Overall Number of Participants Analyzed 143 119 122
Measure Type: Number
Unit of Measure: participants
All AEs 58 46 49
Severe AEs 2 2 2
Adverse drug reactions (ADRs) 22 23 20
AEs leading to discontinuation 7 4 7
ADRs leading to discontinuation 4 4 5
Serious AEs (SAEs) 1 4 5
Deaths 0 0 0
9.Secondary Outcome
Title Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Period
Hide Description A TEAE was any adverse event (AE) occurring after start of treatment and within the time of residual drug effect, i.e., within 1 day for desmopressin. An adverse drug reaction (ADR) was any AE assessed by the investigator as possibly or probably related to study drug.
Time Frame Month 1 of open-label period (Month 4 of treatment)
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Safety analysis set (SAS) for open label-treatment period
Arm/Group Title Placebo Double-Blind / Desmopressin 100 μg Open-Label Desmopressin 50 μg Double-Blind / 100 μg Open-Label Desmopressin 75 μg Double-Blind / 100 μg Open-Label
Hide Arm/Group Description:
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.
Overall Number of Participants Analyzed 124 101 102
Measure Type: Number
Unit of Measure: participants
All AEs 26 23 23
Severe AEs 0 0 1
Adverse drug reactions (ADRs) 9 6 9
AEs leading to discontinuation 2 0 2
ADRs leading to discontinuation 2 0 2
Serious AEs (SAEs) 2 0 1
Deaths 0 0 0
10.Secondary Outcome
Title Minimum Post-Treatment Serum Sodium Levels in the Double-Blind Period
Hide Description Serum sodium levels were monitored at each study visit since hyponatremia is a potential serious adverse event associated with daily doses of desmopressin. The serum sodium level must have been within the normal reference range at the Screening Visit for the participant to be eligible for enrollment. A participant was to be withdrawn from the trial if the serum sodium level was <=125 mmol/L at any time.
Time Frame Day 1 through Month 3 (double-blind period)
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Hide Analysis Population Description
Safety analysis set (SAS)
Arm/Group Title Placebo Double-Blind Desmopressin 50 μg Double-Blind Desmopressin 75 μg Double-Blind
Hide Arm/Group Description:
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Overall Number of Participants Analyzed 143 119 122
Measure Type: Number
Unit of Measure: participants
≤125 mmol/L 0 2 4
126-129 mmol/L 0 0 5
130-134 mmol/L 2 9 12
≥135 mmol/L 141 108 101
11.Secondary Outcome
Title Minimum Post-Treatment Serum Sodium Levels in the Open-Label Period
Hide Description Serum sodium levels were monitored at each study visit since hyponatremia is a potential serious adverse event associated with daily doses of desmopressin. The serum sodium level must have been within the normal reference range at the Screening Visit for the participant to be eligible for enrollment. A participant was to be withdrawn from the trial if the serum sodium level was <=125 mmol/L at any time.
Time Frame Month 1 of open-label period (Month 4 of treatment)
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Hide Analysis Population Description
Safety analysis set (SAS) during open-label treatment period
Arm/Group Title Placebo Double-Blind / Desmopressin 100 μg Open-Label Desmopressin 50 μg Double-Blind / 100 μg Open-Label Desmopressin 75 μg Double-Blind / 100 μg Open-Label
Hide Arm/Group Description:
Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.
Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.
Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.
Overall Number of Participants Analyzed 124 101 102
Measure Type: Number
Unit of Measure: participants
≤125 mmol/L 1 0 1
126-129 mmol/L 3 1 1
130-134 mmol/L 10 12 11
≥135 mmol/L 110 88 89
Time Frame Day 1 through Month 3 for double-blind period; Month 4 for open-label period
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Desmopressin 50 μg Double-Blind Desmopressin 75 μg Double-Blind Placebo Double-Blind Desmopressin 50 μg Double-Blind / 100 μg Open-Label Desmopressin 75 μg Double-Blind / 100 μg Open-Label Placebo Double-Blind / Desmopressin 100 μg Open-Label
Hide Arm/Group Description Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period. Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period. Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.
All-Cause Mortality
Desmopressin 50 μg Double-Blind Desmopressin 75 μg Double-Blind Placebo Double-Blind Desmopressin 50 μg Double-Blind / 100 μg Open-Label Desmopressin 75 μg Double-Blind / 100 μg Open-Label Placebo Double-Blind / Desmopressin 100 μg Open-Label
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Desmopressin 50 μg Double-Blind Desmopressin 75 μg Double-Blind Placebo Double-Blind Desmopressin 50 μg Double-Blind / 100 μg Open-Label Desmopressin 75 μg Double-Blind / 100 μg Open-Label Placebo Double-Blind / Desmopressin 100 μg Open-Label
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/119 (3.36%)   5/122 (4.10%)   1/143 (0.70%)   0/101 (0.00%)   1/102 (0.98%)   2/124 (1.61%) 
Cardiac disorders             
Acute myocardial infarction  1  1/119 (0.84%)  0/122 (0.00%)  0/143 (0.00%)  0/101 (0.00%)  0/102 (0.00%)  0/124 (0.00%) 
General disorders             
Pyrexia  1  0/119 (0.00%)  0/122 (0.00%)  1/143 (0.70%)  0/101 (0.00%)  0/102 (0.00%)  0/124 (0.00%) 
Injury, poisoning and procedural complications             
Rib fracture  1  0/119 (0.00%)  0/122 (0.00%)  0/143 (0.00%)  0/101 (0.00%)  0/102 (0.00%)  1/124 (0.81%) 
Metabolism and nutrition disorders             
Hyponatraemia  1  2/119 (1.68%)  4/122 (3.28%)  0/143 (0.00%)  0/101 (0.00%)  1/102 (0.98%)  1/124 (0.81%) 
Musculoskeletal and connective tissue disorders             
Osteoarthritis  1  1/119 (0.84%)  0/122 (0.00%)  0/143 (0.00%)  0/101 (0.00%)  0/102 (0.00%)  0/124 (0.00%) 
Nervous system disorders             
Transient global amnesia  1  0/119 (0.00%)  1/122 (0.82%)  0/143 (0.00%)  0/101 (0.00%)  0/102 (0.00%)  0/124 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Desmopressin 50 μg Double-Blind Desmopressin 75 μg Double-Blind Placebo Double-Blind Desmopressin 50 μg Double-Blind / 100 μg Open-Label Desmopressin 75 μg Double-Blind / 100 μg Open-Label Placebo Double-Blind / Desmopressin 100 μg Open-Label
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/119 (5.04%)   7/122 (5.74%)   5/143 (3.50%)   0/101 (0.00%)   0/102 (0.00%)   1/124 (0.81%) 
Nervous system disorders             
Headache  1  6/119 (5.04%)  7/122 (5.74%)  5/143 (3.50%)  0/101 (0.00%)  0/102 (0.00%)  1/124 (0.81%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
Results Point of Contact
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Name/Title: Clinical Development Support
Organization: Ferring Pharmaceuticals
EMail: DK0-Disclosure@ferring.com
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Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01262456    
Other Study ID Numbers: FE992026 CS41
First Submitted: December 15, 2010
First Posted: December 17, 2010
Results First Submitted: June 18, 2015
Results First Posted: October 15, 2015
Last Update Posted: October 15, 2015