Trial Outcomes & Findings for Study Investigating the Impact Burden of Nocturia Using the Nocturia Impact Diary (NCT NCT01552343)

NCT ID: NCT01552343

Last Updated: 2017-07-11

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 56 participants
• Primary outcome timeframe: Day 1 (Baseline), Month 1
• Results posted on: 2017-07-11

Participant Flow

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.

Participant milestones

Measure	Placebo 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.	Desmopressin 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.
Overall Study STARTED	29	27
Overall Study COMPLETED	29	27
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study Investigating the Impact Burden of Nocturia Using the Nocturia Impact Diary

Baseline characteristics by cohort

Measure	Placebo n=29 Participants 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.	Desmopressin n=27 Participants 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 n=56 Participants Total of all reporting groups
Age, Customized < 65 years	11 participants n=93 Participants	13 participants n=4 Participants	24 participants n=27 Participants
Age, Customized >=65 years	18 participants n=93 Participants	14 participants n=4 Participants	32 participants n=27 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	12 Participants n=4 Participants	26 Participants n=27 Participants
Sex: Female, Male Male	15 Participants n=93 Participants	15 Participants n=4 Participants	30 Participants n=27 Participants
Race/Ethnicity, Customized White	25 participants n=93 Participants	23 participants n=4 Participants	48 participants n=27 Participants
Race/Ethnicity, Customized Black/African American	4 participants n=93 Participants	2 participants n=4 Participants	6 participants n=27 Participants
Race/Ethnicity, Customized Asian	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Race/Ethnicity, Customized American Indian/Alaska native	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Ethnic Origin Hispanic or Latino	6 participants n=93 Participants	2 participants n=4 Participants	8 participants n=27 Participants
Ethnic Origin Not Hispanic or Latino	23 participants n=93 Participants	25 participants n=4 Participants	48 participants n=27 Participants

PRIMARY outcome

Timeframe: Day 1 (Baseline), Month 1

Population: 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.

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.

Outcome measures

Measure	Male - Desmopressin 75 μg 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 Participants n=56 Participants All study participants	Responders Participants who experienced a reduction from baseline of \>=33% in nocturnal voids at the Month 1	Female - Desmopressin 25 μg 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.
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 Adjusted partial correlation - baseline # of voids	—	0.35 correlation coefficient Interval 0.09 to 0.56	—	—
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 Adj partial correlation - baseline NI total score	—	0.28 correlation coefficient Interval 0.02 to 0.51	—	—
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 Correlation - no adjustments	—	0.31 correlation coefficient Interval 0.05 to 0.53	—	—
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 Adjusted partial correlation - age category	—	0.33 correlation coefficient Interval 0.07 to 0.55	—	—
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 Adjusted partial correlation - gender	—	0.33 correlation coefficient Interval 0.07 to 0.55	—	—

PRIMARY outcome

Timeframe: Day 1 (Baseline), Month 1

Population: 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.

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.

Outcome measures

Measure	Male - Desmopressin 75 μg 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 Participants n=22 Participants All study participants	Responders n=34 Participants Participants who experienced a reduction from baseline of \>=33% in nocturnal voids at the Month 1	Female - Desmopressin 25 μg 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.
Difference in Mean Change From Baseline to Month 1 in Nocturia Impact (NI) Total Scores and Overall Impact Question for Responders and Non-Responders Overall Impact Question (Q12)	—	-4.9 units on a scale Standard Deviation 15.6	-4.9 units on a scale Standard Deviation 18.6	—
Difference in Mean Change From Baseline to Month 1 in Nocturia Impact (NI) Total Scores and Overall Impact Question for Responders and Non-Responders Nocturia Impact (NI) Total Score (Q1-Q11)	—	-2.6 units on a scale Standard Deviation 6.8	-13.3 units on a scale Standard Deviation 17.9	—

PRIMARY outcome

Timeframe: Day 1 (Baseline), Month 1

Population: 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.

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.

Outcome measures

Measure	Male - Desmopressin 75 μg 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 Participants n=56 Participants All study participants	Responders Participants who experienced a reduction from baseline of \>=33% in nocturnal voids at the Month 1	Female - Desmopressin 25 μg 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.
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 Nocturia Impact (NI) Total Score (Q1-Q11)	—	0.73 units on a scale Standard Deviation 14.7	—	—
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 Overall Impact Question (Q12)	—	-0.00 units on a scale Standard Deviation 17.5	—	—

SECONDARY outcome

Timeframe: Screening (Day -20 to Day -18), Baseline (Day -2 to Day 1) and Treatment (Day 28 to Day 30)

Population: 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.

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).

Outcome measures

Measure	Male - Desmopressin 75 μg 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 Participants n=56 Participants All study participants	Responders Participants who experienced a reduction from baseline of \>=33% in nocturnal voids at the Month 1	Female - Desmopressin 25 μg 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.
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values Treatment Day 29	—	0.914 ratio of variance Interval 0.877 to 0.944	—	—
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values Screening Day -20	—	0.915 ratio of variance Interval 0.878 to 0.945	—	—
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values Screening Day -19	—	0.925 ratio of variance Interval 0.892 to 0.951	—	—
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values Screening Day -18	—	0.923 ratio of variance Interval 0.89 to 0.95	—	—
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values Baseline Day -2	—	0.939 ratio of variance Interval 0.912 to 0.96	—	—
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values Baseline Day -1	—	0.941 ratio of variance Interval 0.915 to 0.961	—	—
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values Baseline Day 1	—	0.943 ratio of variance Interval 0.919 to 0.963	—	—
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values Treatment Day 28	—	0.920 ratio of variance Interval 0.885 to 0.948	—	—
Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values Treatment Day 30	—	0.898 ratio of variance Interval 0.853 to 0.933	—	—

SECONDARY outcome

Timeframe: Screening (Day -20), Baseline (Day 1)

Population: 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.

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).

Outcome measures

Measure	Male - Desmopressin 75 μg 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 Participants n=33 Participants All study participants	Responders n=23 Participants Participants who experienced a reduction from baseline of \>=33% in nocturnal voids at the Month 1	Female - Desmopressin 25 μg 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.
Construct Validity For the Nocturia Impact (NI) Total Scores and Overall Impact Question (Q12) for Participants With High/Low Number of Nocturnal Voids Nocturia Impact (NI) Total Score: Screening	—	28.1 units on a scale Standard Deviation 20.4	36.7 units on a scale Standard Deviation 23.0	—
Construct Validity For the Nocturia Impact (NI) Total Scores and Overall Impact Question (Q12) for Participants With High/Low Number of Nocturnal Voids Nocturia Impact (NI) Total Score: Baseline	—	25.7 units on a scale Standard Deviation 20.4	39.3 units on a scale Standard Deviation 25.7	—
Construct Validity For the Nocturia Impact (NI) Total Scores and Overall Impact Question (Q12) for Participants With High/Low Number of Nocturnal Voids Overall Impact Question (Q12): Screening	—	40.4 units on a scale Standard Deviation 27.3	56.2 units on a scale Standard Deviation 30.1	—
Construct Validity For the Nocturia Impact (NI) Total Scores and Overall Impact Question (Q12) for Participants With High/Low Number of Nocturnal Voids Overall Impact Question (Q12): Baseline	—	35.6 units on a scale Standard Deviation 28.4	53.3 units on a scale Standard Deviation 34.7	—

SECONDARY outcome

Timeframe: Baseline (Day -2 to Day 1), Treatment (Day 28-30)

Population: 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.

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.

Outcome measures

Measure	Male - Desmopressin 75 μg 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 Participants n=27 Participants All study participants	Responders n=29 Participants Participants who experienced a reduction from baseline of \>=33% in nocturnal voids at the Month 1	Female - Desmopressin 25 μg 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.
Change From Baseline to Month 1 on Nocturia Impact (NI) Total Score	—	-8.5 units on a scale Standard Deviation 13.7	-9.64 units on a scale Standard Deviation 17.2	—

SECONDARY outcome

Timeframe: Day 1 up to 1 month

Population: Safety analysis set

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.

Outcome measures

Measure	Male - Desmopressin 75 μg n=15 Participants 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 Participants n=14 Participants All study participants	Responders n=15 Participants Participants who experienced a reduction from baseline of \>=33% in nocturnal voids at the Month 1	Female - Desmopressin 25 μg n=12 Participants 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.
Minimum Post-Treatment Serum Sodium Levels <=125 mmol/L	0 participants	0 participants	0 participants	0 participants
Minimum Post-Treatment Serum Sodium Levels >125 - <130 mmol/L	0 participants	0 participants	0 participants	0 participants
Minimum Post-Treatment Serum Sodium Levels >=130 - 135 mmol/L	1 participants	0 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: Day 1 up to 1 month

Population: Safety analysis set

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.

Outcome measures

Measure	Male - Desmopressin 75 μg n=15 Participants 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 Participants n=14 Participants All study participants	Responders n=15 Participants Participants who experienced a reduction from baseline of \>=33% in nocturnal voids at the Month 1	Female - Desmopressin 25 μg n=12 Participants 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.
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) All adverse events (AEs)	0 participants	2 participants	1 participants	2 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) Deaths	0 participants	0 participants	0 participants	0 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) Serious AEs	0 participants	0 participants	0 participants	0 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) AEs leading to discontinuation	0 participants	0 participants	0 participants	0 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) Severe AEs	0 participants	0 participants	0 participants	0 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) Adverse drug reactions (ADRs)	0 participants	0 participants	0 participants	1 participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Desmopressin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Clinical Development Support

Ferring Pharmaceuticals

Email: DK0-Disclosure@ferring.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER