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Study Investigating the Impact Burden of Nocturia Using the Nocturia Impact Diary (IMPACT)

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ClinicalTrials.gov Identifier: NCT01552343
Recruitment Status : Completed
First Posted : March 13, 2012
Results First Posted : May 5, 2017
Last Update Posted : July 11, 2017
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Nocturia
Interventions Drug: Desmopressin
Drug: Placebo
Enrollment 56
Recruitment Details  
Pre-assignment Details A total of 67 subjects were screened and 11 subjects were screening failures: 5 due to signs of renal impairment, 4 did not have >=2 nocturnal voids every night in the 3-day screening period, 1 had uncontrolled diabetes mellitus, and 1 was leaving town for an undetermined period of time.
Arm/Group Title Placebo Desmopressin
Hide Arm/Group Description Female and male participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month. Female participants took 1 desmopressin 25 μg tablet and male participants took 1 tablet 75 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Period Title: Overall Study
Started 29 27
Completed 29 27
Not Completed 0 0
Arm/Group Title Placebo Desmopressin Total
Hide Arm/Group Description Female and male participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month. Female participants took 1 desmopressin 25 μg tablet and male participants took 1 tablet 75 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month. Total of all reporting groups
Overall Number of Baseline Participants 29 27 56
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 29 participants 27 participants 56 participants
< 65 years 11 13 24
>=65 years 18 14 32
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 27 participants 56 participants
Female
14
  48.3%
12
  44.4%
26
  46.4%
Male
15
  51.7%
15
  55.6%
30
  53.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 29 participants 27 participants 56 participants
White 25 23 48
Black/African American 4 2 6
Asian 0 1 1
American Indian/Alaska native 0 1 1
Ethnic Origin  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 29 participants 27 participants 56 participants
Hispanic or Latino 6 2 8
Not Hispanic or Latino 23 25 48
1.Primary Outcome
Title The Pearson Correlation Coefficient Between Change From Baseline to Month 1 in Number of Nocturnal Voids and Change From Baseline to Month 1 in Nocturia Impact (NI) Diary Total Score
Hide Description

This outcome is a measure of sensitivity of the NI Diary to change in nocturia.

The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). Responses are scored from 0 (no impact) to 4 (highest impact); a lowering of score equals a decrease in impact caused by nocturia. The NI total score is the sum of the 11 core items scores. The NI total score was analyzable only if all 11 items (Q1-Q11) had non-missing responses. Otherwise, it was defined as missing. Missing values were not imputed. The average over the 3-day diary period prior to baseline (Day 1) and Month 1 was used for the overall impact score.

The correlation was estimated using Fisher’s z transformation, i.e. the NI total score was based on a standardized scale from 0 (lowest impact) to 100 (highest impact).

Corresponding adjusted partial correlation coefficients were based on adjustments for mean number of Baseline voids, Baseline NI total score, age, and gender.

Time Frame Day 1 (Baseline), Month 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Study results are reported as per the pre-planned statistical analysis plan on combined treatment groups. The study is a psychometric evaluation of a new PRO tool and is not designed to show treatment difference between active and placebo.
Arm/Group Title All Participants
Hide Arm/Group Description:
All study participants
Overall Number of Participants Analyzed 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: correlation coefficient
Correlation - no adjustments
0.31
(0.05 to 0.53)
Adjusted partial correlation - baseline # of voids
0.35
(0.09 to 0.56)
Adj partial correlation - baseline NI total score
0.28
(0.02 to 0.51)
Adjusted partial correlation - age category
0.33
(0.07 to 0.55)
Adjusted partial correlation - gender
0.33
(0.07 to 0.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Participants
Comments Correlation - no adjustments
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0187
Comments The a priori threshold for statistical significance was 0.05.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Participants
Comments Partial correlation - baseline # of voids
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0094
Comments The a priori threshold for statistical significance was 0.05.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection All Participants
Comments Partial correlation - baseline NI total score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0383
Comments The a priori threshold for statistical significance was 0.05.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection All Participants
Comments Partial correlation - age category
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0133
Comments The a priori threshold for statistical significance was 0.05.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection All Participants
Comments Partial correlation - gender
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0128
Comments [Not Specified]
Method t-test, 2 sided
Comments The a priori threshold for statistical significance was 0.05.
2.Primary Outcome
Title Difference in Mean Change From Baseline to Month 1 in Nocturia Impact (NI) Total Scores and Overall Impact Question for Responders and Non-Responders
Hide Description

This outcome is a measure of sensitivity of the NI Diary to change in nocturia.

The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). The NI total score is defined as the sum of the 11 core items scores.

The overall impact question (Q12) and the NI total score were transformed using Fisher's z transformation, i.e. the scores were based on a standardized scale from 0 (lowest impact) to 100 (highest impact).

The difference in mean change in NI total score for subjects who experienced a reduction from baseline of <33% in nocturnal voids at the Month 1 visit (non-responders) versus those with a reduction in nocturnal voids from Baseline of ≥33% (responders) was estimated.

Time Frame Day 1 (Baseline), Month 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Study results are reported as per the pre-planned statistical analysis plan on combined treatment groups. The study is a psychometric evaluation of a new PRO tool and is not designed to show treatment difference between active and placebo.
Arm/Group Title Non-Responders Responders
Hide Arm/Group Description:
Participants who experienced a reduction from baseline of <33% in nocturnal voids at the Month 1
Participants who experienced a reduction from baseline of >=33% in nocturnal voids at the Month 1
Overall Number of Participants Analyzed 22 34
Mean (Standard Deviation)
Unit of Measure: units on a scale
Nocturia Impact (NI) Total Score (Q1-Q11) -2.6  (6.8) -13.3  (17.9)
Overall Impact Question (Q12) -4.9  (15.6) -4.9  (18.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-Responders, Responders
Comments Nocturia Impact (NI) Total Score (Q1-Q11)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 10.7
Confidence Interval (2-Sided) 95%
2.7 to 18.8
Estimation Comments Non-Responders - Responders
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Non-Responders, Responders
Comments Overall Impact Question (Q12)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-9.6 to 9.6
Estimation Comments Non-Responders - Responders
3.Primary Outcome
Title Cohen's D Effect Size in Responsiveness in the Nocturia Impact (NI) Total Scores and Overall Impact Question as Measured From Baseline (Day 1) to Month 1
Hide Description

The responsiveness of the NI Diary was measured with Cohen’s D effect size. The effect size was calculated for active treatment versus placebo, based on change from Baseline to Month 1. The effect size was evaluated as “small,” “medium,” or “large” if D was <=0.35, >0.35 - 0.65, or >0.65, respectively.

Mean values are the Cohen's D effect size. Standard deviation is the pooled standard deviation.

Time Frame Day 1 (Baseline), Month 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Study results are reported as per the pre-planned statistical analysis plan on combined treatment groups. The study is a psychometric evaluation of a new PRO tool and is not designed to show treatment difference between active and placebo.
Arm/Group Title All Participants
Hide Arm/Group Description:
All study participants
Overall Number of Participants Analyzed 56
Mean (Standard Deviation)
Unit of Measure: units on a scale
Nocturia Impact (NI) Total Score (Q1-Q11) 0.73  (14.7)
Overall Impact Question (Q12) -0.00  (17.5)
4.Secondary Outcome
Title Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values
Hide Description

Cronbach’s alpha (CA) is a measure of the internal consistency of the Nocturia Impact (NI) Total scores. Higher scores indicate a more reliable (precise) instrument. A value of 0.70 set as the benchmark for declaring the scale as internally consistent.

Cronbach's alpha was assessed for each of the three consecutive days NI diaries were completed during screening (Day -20 to Day -18), baseline (Day -2 to Day 1) and Month 1 (Day 28 to Day 30).

Time Frame Screening (Day -20 to Day -18), Baseline (Day -2 to Day 1) and Treatment (Day 28 to Day 30)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Study results are reported as per the pre-planned statistical analysis plan on combined treatment groups. The study is a psychometric evaluation of a new PRO tool and is not designed to show treatment difference between active and placebo.
Arm/Group Title All Participants
Hide Arm/Group Description:
All study participants
Overall Number of Participants Analyzed 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: ratio of variance
Screening Day -20
0.915
(0.878 to 0.945)
Screening Day -19
0.925
(0.892 to 0.951)
Screening Day -18
0.923
(0.890 to 0.950)
Baseline Day -2
0.939
(0.912 to 0.960)
Baseline Day -1
0.941
(0.915 to 0.961)
Baseline Day 1
0.943
(0.919 to 0.963)
Treatment Day 28
0.920
(0.885 to 0.948)
Treatment Day 29
0.914
(0.877 to 0.944)
Treatment Day 30
0.898
(0.853 to 0.933)
5.Secondary Outcome
Title Construct Validity For the Nocturia Impact (NI) Total Scores and Overall Impact Question (Q12) for Participants With High/Low Number of Nocturnal Voids
Hide Description

The known group validity was assessed by comparing participants who experienced ≥3 nocturnal voids to those who experienced <3 nocturnal voids, using the average over 3 days for the Screening and Baseline diaries. Results are reported for the NI Total Scores and the Overall Impact Question (Q12).

The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). The NI total score is defined as the sum of the 11 core items scores.

The overall impact question (Q12) and the NI total score were transformed using Fisher's z transformation, i.e. the scores were based on a standardized scale from 0 (lowest impact) to 100 (highest impact).

Time Frame Screening (Day -20), Baseline (Day 1)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Study results are reported as per the pre-planned statistical analysis plan on combined treatment groups. The study is a psychometric evaluation of a new PRO tool and is not designed to show treatment difference between active and placebo.
Arm/Group Title < 3 Voids >= 3 Voids
Hide Arm/Group Description:
Study participants who had <3 voids average from the screening and baseline diaries.
Study participants who had >=3 voids average from the screening and baseline diaries.
Overall Number of Participants Analyzed 33 23
Mean (Standard Deviation)
Unit of Measure: units on a scale
Nocturia Impact (NI) Total Score: Screening 28.1  (20.4) 36.7  (23.0)
Nocturia Impact (NI) Total Score: Baseline 25.7  (20.4) 39.3  (25.7)
Overall Impact Question (Q12): Screening 40.4  (27.3) 56.2  (30.1)
Overall Impact Question (Q12): Baseline 35.6  (28.4) 53.3  (34.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection < 3 Voids, >= 3 Voids
Comments Nocturia Impact (NI) Total Score: Screening
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1471
Comments The a priori threshold for statistical significance was 0.05.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -8.6
Confidence Interval (2-Sided) 95%
-20.3 to 3.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection < 3 Voids, >= 3 Voids
Comments Nocturia Impact (NI) Total Score: Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0318
Comments The a priori threshold for statistical significance was 0.05.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -13.6
Confidence Interval (2-Sided) 95%
-26.0 to -1.2
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection < 3 Voids, >= 3 Voids
Comments Overall Impact Question (Q12): Screening
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0463
Comments The a priori threshold for statistical significance was 0.05.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -15.8
Confidence Interval (2-Sided) 95%
-31.2 to -0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection < 3 Voids, >= 3 Voids
Comments Overall Impact Question (Q12): Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0413
Comments The a priori threshold for statistical significance was 0.05.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -17.7
Confidence Interval (2-Sided) 95%
-34.6 to -0.7
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline to Month 1 on Nocturia Impact (NI) Total Score
Hide Description The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). Responses are scored from 0 (no impact) to 4 (highest impact); the NI total score is the sum of the 11 core items scores (range of 0-44) which is then transformed to a 0-100 scale (high score indicates high impact). The NI total score was analyzable only if all 11 items (Q1-Q11) had non-missing responses. Otherwise, it was defined as missing. Missing values were not imputed. The average over the 3-day diary period prior to baseline (Day 1) and Month 1 was used for the overall impact score. Negative change from baseline scores indicate a decrease in impact caused by nocturia.
Time Frame Baseline (Day -2 to Day 1), Treatment (Day 28-30)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. The study is a psychometric evaluation of a new PRO tool and is not designed to show treatment difference between active and placebo.
Arm/Group Title Desmopressin Placebo
Hide Arm/Group Description:
Female participants took 1 tablet of 25 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month. Male participants took 1 tablet of 75 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Overall Number of Participants Analyzed 27 29
Mean (Standard Deviation)
Unit of Measure: units on a scale
-8.5  (13.7) -9.64  (17.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmopressin, Placebo
Comments Treatment effect. NI total scores are transformed to a 0-100 scale where 0 is good and 100 bad.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9647
Comments [Not Specified]
Method ANCOVA
Comments Covariates baseline score, treatment and age stratum (<65, >=65).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-6.6 to 6.3
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Minimum Post-Treatment Serum Sodium Levels
Hide Description Serum sodium levels were monitored since hyponatremia is a potential serious adverse event associated with daily doses of desmopressin. 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 up to 1 month
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Female - Placebo Male - Placebo Female - Desmopressin 25 μg Male - Desmopressin 75 μg
Hide Arm/Group Description:
Female participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Male participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Female participants took 1 tablet of 25 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Male participants took 1 tablet 75 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Overall Number of Participants Analyzed 14 15 12 15
Measure Type: Number
Unit of Measure: participants
<=125 mmol/L 0 0 0 0
>125 - <130 mmol/L 0 0 0 0
>=130 - 135 mmol/L 0 0 2 1
8.Secondary Outcome
Title Summary of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description A TEAE was any adverse event occurring after start of treatment and within the time of residual drug effect, i.e. within one day of the last dose of desmopressin.
Time Frame Day 1 up to 1 month
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Female - Placebo Male - Placebo Female - Desmopressin 25 μg Male - Desmopressin 75 μg
Hide Arm/Group Description:
Female participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Male participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Female participants took 1 tablet of 25 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Male participants took 1 tablet 75 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
Overall Number of Participants Analyzed 14 15 12 15
Measure Type: Number
Unit of Measure: participants
All adverse events (AEs) 2 1 2 0
Deaths 0 0 0 0
Serious AEs 0 0 0 0
AEs leading to discontinuation 0 0 0 0
Severe AEs 0 0 0 0
Adverse drug reactions (ADRs) 0 0 1 0
Time Frame Day 1 up to Month 1
Adverse Event Reporting Description A TEAE was any adverse event occurring after start of treatment and within the time of residual drug effect, i.e. within one day of the last dose of desmopressin.
 
Arm/Group Title Placebo Desmopressin
Hide Arm/Group Description Female and male participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month. Female participants took 1 desmopressin 25 μg tablet and male participants took 1 tablet 75 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.
All-Cause Mortality
Placebo Desmopressin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Desmopressin
Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)   0/27 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Desmopressin
Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)   0/27 (0.00%) 
This was a patient reported outcome (PRO) validation study on a highly selective population (responders on active treatment and non-responsers on placebo from CS40/CS41) and not powered to look at efficacy.
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
Name/Title: Clinical Development Support
Organization: Ferring Pharmaceuticals
Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01552343     History of Changes
Other Study ID Numbers: 000034
First Submitted: March 5, 2012
First Posted: March 13, 2012
Results First Submitted: November 21, 2016
Results First Posted: May 5, 2017
Last Update Posted: July 11, 2017