Trial Outcomes & Findings for Comparative Trial to Investigate the Dose-Response of 4 Different Dose Levels of Minirin Melt and Placebo (NCT NCT01184859)

Results Overview

Participants were water-loaded to suppress the endogenous release of vasopressin, thus all antidiuretic activity was generated by desmopressin only. Water-loading was initiated 2 hours before dosing on Day 1. Urine volume was registered and samples for osmolality check were collected every 30 minutes as long as there was an antidiuretic action defined as a urine production \<0.12 mL/kg/min. The hydration should have lasted until end of action, defined as when the urine production returned to \>0.12 mL/kg/min, but no longer than 12 hours.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

116 participants

Primary outcome timeframe

Day 1

Results posted on

2012-05-25

Participant Flow

139 patients randomized and 116 treated. Withdrawals during the screening period were due to urine production did not meet \>0.12 mL/kg/min within 2 hours of dosing (22 patients) and violation of inclusion/exclusion criteria (1 patient).

Participant milestones

Participant milestones
Measure	Placebo Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Period 1: Single Dose STARTED	23	25	22	22	24
Period 1: Single Dose Full Analysis Set (FAS)	23	23	22	21	24
Period 1: Single Dose Per Protocol (PP)	23	23	22	21	23
Period 1: Single Dose COMPLETED	23	23	22	22	23
Period 1: Single Dose NOT COMPLETED	0	2	0	0	1
Washout Period STARTED	23	23	22	22	23
Washout Period COMPLETED	23	23	22	22	23
Washout Period NOT COMPLETED	0	0	0	0	0
Period 2: Daily Dose for 28 Days STARTED	23	23	22	22	23
Period 2: Daily Dose for 28 Days COMPLETED	22	23	22	22	22
Period 2: Daily Dose for 28 Days NOT COMPLETED	1	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 100µg Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Period 1: Single Dose Insufficient urine production	0	1	0
Period 1: Single Dose Protocol Violation	0	1	0
Period 1: Single Dose Adverse Event	0	0	1
Period 2: Daily Dose for 28 Days Withdrawal by Subject	0	0	1
Period 2: Daily Dose for 28 Days Adverse Event	1	0	0

Baseline Characteristics

Comparative Trial to Investigate the Dose-Response of 4 Different Dose Levels of Minirin Melt and Placebo

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=23 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=23 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=22 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=21 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=24 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.	Total n=113 Participants Total of all reporting groups
Age Continuous	64.3 years STANDARD_DEVIATION 6.4 • n=5 Participants	67.0 years STANDARD_DEVIATION 5.6 • n=7 Participants	65.5 years STANDARD_DEVIATION 6.0 • n=5 Participants	64.9 years STANDARD_DEVIATION 7.1 • n=4 Participants	65.3 years STANDARD_DEVIATION 5.6 • n=21 Participants	65.4 years STANDARD_DEVIATION 6.1 • n=8 Participants
Age, Customized >=55 and <65 years	12 participants n=5 Participants	8 participants n=7 Participants	10 participants n=5 Participants	10 participants n=4 Participants	12 participants n=21 Participants	52 participants n=8 Participants
Age, Customized >=65 and <76 years	11 participants n=5 Participants	15 participants n=7 Participants	12 participants n=5 Participants	11 participants n=4 Participants	12 participants n=21 Participants	61 participants n=8 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	12 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants	12 Participants n=21 Participants	58 Participants n=8 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	10 Participants n=4 Participants	12 Participants n=21 Participants	55 Participants n=8 Participants
Number of Nocturnal Voids	2.16 nocturnal voids STANDARD_DEVIATION 0.26 • n=5 Participants	2.43 nocturnal voids STANDARD_DEVIATION 0.51 • n=7 Participants	2.45 nocturnal voids STANDARD_DEVIATION 0.45 • n=5 Participants	2.29 nocturnal voids STANDARD_DEVIATION 0.44 • n=4 Participants	2.26 nocturnal voids STANDARD_DEVIATION 0.38 • n=21 Participants	2.32 nocturnal voids STANDARD_DEVIATION 0.42 • n=8 Participants
Number of Daytime Voids	7.67 daytime voids STANDARD_DEVIATION 1.48 • n=5 Participants	7.97 daytime voids STANDARD_DEVIATION 1.91 • n=7 Participants	8.70 daytime voids STANDARD_DEVIATION 1.53 • n=5 Participants	8.67 daytime voids STANDARD_DEVIATION 1.99 • n=4 Participants	8.33 daytime voids STANDARD_DEVIATION 1.65 • n=21 Participants	8.26 daytime voids STANDARD_DEVIATION 1.74 • n=8 Participants
Number of 24-hour Voids	9.83 voids STANDARD_DEVIATION 1.52 • n=5 Participants	10.41 voids STANDARD_DEVIATION 1.94 • n=7 Participants	11.15 voids STANDARD_DEVIATION 1.79 • n=5 Participants	10.95 voids STANDARD_DEVIATION 2.12 • n=4 Participants	10.60 voids STANDARD_DEVIATION 1.60 • n=21 Participants	10.58 voids STANDARD_DEVIATION 1.83 • n=8 Participants
Nocturnal Urine Volume	634.78 mL STANDARD_DEVIATION 210.54 • n=5 Participants	568.55 mL STANDARD_DEVIATION 227.40 • n=7 Participants	613.06 mL STANDARD_DEVIATION 182.47 • n=5 Participants	635.87 mL STANDARD_DEVIATION 211.53 • n=4 Participants	631.78 mL STANDARD_DEVIATION 175.02 • n=21 Participants	616.64 mL STANDARD_DEVIATION 200.13 • n=8 Participants
24-Hour Urine Volume	1742.32 mL STANDARD_DEVIATION 344.99 • n=5 Participants	1632.17 mL STANDARD_DEVIATION 454.75 • n=7 Participants	1881.67 mL STANDARD_DEVIATION 399.42 • n=5 Participants	1848.32 mL STANDARD_DEVIATION 497.96 • n=4 Participants	1785.65 mL STANDARD_DEVIATION 404.67 • n=21 Participants	1775.93 mL STANDARD_DEVIATION 423.67 • n=8 Participants

PRIMARY outcome

Timeframe: Day 1

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance.

Participants were water-loaded to suppress the endogenous release of vasopressin, thus all antidiuretic activity was generated by desmopressin only. Water-loading was initiated 2 hours before dosing on Day 1. Urine volume was registered and samples for osmolality check were collected every 30 minutes as long as there was an antidiuretic action defined as a urine production \<0.12 mL/kg/min. The hydration should have lasted until end of action, defined as when the urine production returned to \>0.12 mL/kg/min, but no longer than 12 hours.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=23 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=22 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=21 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 1	0.00 hours Standard Deviation 0.00	0.09 hours Standard Deviation 0.32	2.00 hours Standard Deviation 3.56	3.45 hours Standard Deviation 2.88	5.74 hours Standard Deviation 2.99

PRIMARY outcome

Timeframe: 3 days between study days -6 to 0 (Baseline), and days 25 to 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average number of nocturnal voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=22 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=20 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=19 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in Number of Nocturnal Voids After 28 Days of Treatment - Period 2	-0.735 nocturnal voids Interval -1.049 to -0.421	-1.007 nocturnal voids Interval -1.32 to -0.695	-1.282 nocturnal voids Interval -1.583 to -0.981	-1.589 nocturnal voids Interval -1.903 to -1.274	-1.624 nocturnal voids Interval -1.999 to -1.248

SECONDARY outcome

Timeframe: Day 1

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance.

Area under the urine osmolality curve, from dose administration to end of action (AUCosm).

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=23 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=22 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=21 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Area Under the Urine Osmolality Curve (AUCosm)	0.00 h*mOsm/kg Standard Deviation 0.00	24.67 h*mOsm/kg Standard Deviation 97.50	852.00 h*mOsm/kg Standard Deviation 1576.10	1551.01 h*mOsm/kg Standard Deviation 1501.21	3112.53 h*mOsm/kg Standard Deviation 2131.69

SECONDARY outcome

Timeframe: Day 1

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance.

Area under the urine production curve, from dose administration to end of action (AUCurine prod)

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=23 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=22 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=21 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=23 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Area Under the Urine Production Curve (AUCurine Prod)	59.34 h*mL Standard Deviation 153.78	214.24 h*mL Standard Deviation 266.86	297.17 h*mL Standard Deviation 322.51	522.99 h*mL Standard Deviation 283.90	537.08 h*mL Standard Deviation 330.67

SECONDARY outcome

Timeframe: Day 1

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance.

Urine volume was registered and samples for osmolality check were collected every 30 minutes as long as there was an antidiuretic action defined as a urine production \<0.12 mL/kg/min. The hydration due to water-loading should have lasted until end of action, defined as when the urine production returned to \>0.12 mL/kg/min, but no longer than 12 hours.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=23 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=22 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=21 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=23 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Time When Urine Production <0.12 ml/kg/Min	0.41 hours Standard Deviation 1.15	1.67 hours Standard Deviation 2.16	3.50 hours Standard Deviation 4.17	6.05 hours Standard Deviation 3.56	8.20 hours Standard Deviation 2.59

SECONDARY outcome

Timeframe: 3 days between study days -6 to 0 (Baseline), and days 25 to 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

Duration of first period of undisturbed sleep is defined as the length of time from initial sleep to first awakening. Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average length of first period of undisturbed sleep of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=22 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=20 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=19 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in Duration of First Period of Undisturbed Sleep After 28 Days of Treatment - Period 2	68.39 minutes Standard Deviation 93.32	101.85 minutes Standard Deviation 120.26	113.45 minutes Standard Deviation 120.22	190.77 minutes Standard Deviation 124.32	194.25 minutes Standard Deviation 99.17

SECONDARY outcome

Timeframe: 3 days between study days -6 to 0 (Baseline), and days 25 to 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

Total sleep time is defined as the time spent asleep from initial sleep to final awakening. Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average of the total time asleep of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=22 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=20 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=19 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in Total Sleep Time at Approximately Day 32	2.47 minutes Standard Deviation 49.94	-11.86 minutes Standard Deviation 48.57	-33.04 minutes Standard Deviation 116.09	6.81 minutes Standard Deviation 69.04	14.07 minutes Standard Deviation 54.06

SECONDARY outcome

Timeframe: 3 days between study days -6 to 0 (Baseline), and days 25 to 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

Number of daytime voids was recorded over three consecutive days per week in diaries kept by study participants. The average number of daytime voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=22 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=20 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=19 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in Number of Daytime Voids at Approximately Day 32	0.49 voids Standard Deviation 1.33	0.68 voids Standard Deviation 1.53	0.15 voids Standard Deviation 1.66	0.23 voids Standard Deviation 1.51	0.63 voids Standard Deviation 1.74

SECONDARY outcome

Timeframe: 3 days between study days -6 to 0 (Baseline), and days 25 to 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

Number of voids in 24 hours was recorded over three consecutive days per week in diaries kept by study participants. The average number of 24-hour voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=22 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=20 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=19 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in Number of 24-hour Urine Voids at Approximately Day 32	-0.15 voids Standard Deviation 1.71	-0.47 voids Standard Deviation 1.93	-1.19 voids Standard Deviation 1.85	-1.33 voids Standard Deviation 1.81	-0.96 voids Standard Deviation 1.69

SECONDARY outcome

Timeframe: 3 days between study days -6 to 0 (Baseline), and days 25 to 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

Nocturnal urine volume was recorded over three consecutive days per week in diaries kept by study participants. The average nocturnal urine volume of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=22 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=20 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=19 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in Nocturnal Urine Volume at Approximately Day 32	-114.70 ml Standard Deviation 224.53	-140.68 ml Standard Deviation 168.62	-209.87 ml Standard Deviation 262.89	-295.02 ml Standard Deviation 196.71	-333.22 ml Standard Deviation 154.05

SECONDARY outcome

Timeframe: 3 days between study days -6 to 0 (Baseline), and days 25 to 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

Twenty-four hour urine volume was recorded over three consecutive days per week in diaries kept by study participants. The average 24-hour urine volume of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=22 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=20 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=19 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in 24-Hour Urine Volume at Approximately Day 32	-104.47 ml Standard Deviation 386.27	-19.47 ml Standard Deviation 371.72	-201.83 ml Standard Deviation 487.49	-270.53 ml Standard Deviation 344.29	-187.25 ml Standard Deviation 369.61

SECONDARY outcome

Timeframe: 3 days between study days -6 to 0 (Baseline), and days 25 to 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

Twenty-four hour urine volume was recorded over three consecutive days per week in diaries kept by study participants. Urine volume per body weight was calculated. The average 24-hour urine volume per kg of body weight of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=22 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=20 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=19 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in 24-Hour Urine Production Per Body Weight at Approximately Day 32	-2.017 ml/kg Standard Deviation 6.205	-0.096 ml/kg Standard Deviation 6.814	-3.523 ml/kg Standard Deviation 7.621	-4.573 ml/kg Standard Deviation 6.183	-3.058 ml/kg Standard Deviation 6.263

SECONDARY outcome

Timeframe: 3 days between study days -6 to 0 (Baseline), and days 25 to 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

Nocturnal polyuria index is defined as a proportion of nocturnal urine volume to the 24-hour urine volume. Urine volume and time of day of those voids was recorded over three consecutive days per week in diaries kept by study participants. The average nocturnal polyuria index of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=22 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=20 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=19 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in Nocturnal Polyuria Index at Approximately Day 32	-4.72 nocturnal urine volume / 24-hour urine Standard Deviation 6.75	-7.82 nocturnal urine volume / 24-hour urine Standard Deviation 6.65	-8.61 nocturnal urine volume / 24-hour urine Standard Deviation 9.28	-13.56 nocturnal urine volume / 24-hour urine Standard Deviation 9.72	-16.00 nocturnal urine volume / 24-hour urine Standard Deviation 6.87

SECONDARY outcome

Timeframe: Approximately Day 4 (start of period 2) and Day 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

N-QoL assesses the impact of nocturia on quality of life (QoL) and treatment outcomes. N-QoL is a self-administered questionnaire with 13 items using scales of 0 = no negative impact to QoL to the upper number = signficant negative impact to QoL. The sleep/energy domain consists of 7 questions with a scale of 0 to 28. The bother/concern domain consists of 5 questions for a scale of 0 to 20. The 13th question is an overall assessment scored from 0 to 10. The Total Score includes all 13 questions with a scale of 0 (no negative impact to QoL) to 58 (significant negative impact to QoL).

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=23 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=22 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=21 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=22 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in Nocturia-Related Quality of Life Based on Evaluation Provided by Nocturia Quality of Life Questionnaire (N-QoL) at Approximately Day 32 Sleep/Energy subscale	7.77 units on a scale Standard Deviation 11.66	10.69 units on a scale Standard Deviation 15.33	13.26 units on a scale Standard Deviation 15.46	12.30 units on a scale Standard Deviation 10.82	8.52 units on a scale Standard Deviation 12.23
Change From Baseline in Nocturia-Related Quality of Life Based on Evaluation Provided by Nocturia Quality of Life Questionnaire (N-QoL) at Approximately Day 32 Bother/Concern subscale	6.36 units on a scale Standard Deviation 19.02	8.99 units on a scale Standard Deviation 16.91	16.33 units on a scale Standard Deviation 18.35	10.67 units on a scale Standard Deviation 19.37	10.15 units on a scale Standard Deviation 14.00
Change From Baseline in Nocturia-Related Quality of Life Based on Evaluation Provided by Nocturia Quality of Life Questionnaire (N-QoL) at Approximately Day 32 Total Score	7.04 units on a scale Standard Deviation 14.05	9.98 units on a scale Standard Deviation 14.65	14.78 units on a scale Standard Deviation 16.28	11.44 units on a scale Standard Deviation 13.00	9.39 units on a scale Standard Deviation 11.11

SECONDARY outcome

Timeframe: Approximately Day 4 (start of period 2) and Day 32

Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.

The Global Score of the Pittsburgh Sleep Quality Index (PSQI) is comprised of Questions 2-9 with a total scale of 0 (no difficulty sleeping) to 21 (severe difficulty). The change in Global Score is Global Score at the end of period 2 (day 32) - Global Score at the start of Period 2 (day 4). A negative change indicates an improvement in quality of life.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=23 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=21 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=21 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=21 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Change From Baseline in Sleep Related Quality of Life Based on the Global Score of the Pittsburgh Sleep Quality Index (PSQI) at Approximately Day 32	-1.2 units on a scale Standard Deviation 2.0	-0.6 units on a scale Standard Deviation 2.3	-1.5 units on a scale Standard Deviation 2.2	-1.4 units on a scale Standard Deviation 2.5	-1.3 units on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: Days 4- 32

Population: Safety population which included all randomised and exposed participants. Participants were analysed according to the actual treatment received.

Serum sodium levels were monitored throughout the trial as part of the clinical chemistry panel. If the value was ≤125 mEq/L, the participant was to be withdrawn from the trial and treatment stopped immediately. This outcome reports participants' lowest recorded serum sodium levels during the second treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg n=23 Participants Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg n=22 Participants Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg n=22 Participants Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg n=23 Participants Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) >= 135 mEq/L	23 participants	23 participants	21 participants	21 participants	23 participants
Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) >=130 mEq/L to <135 mEq/L	0 participants	0 participants	1 participants	1 participants	0 participants
Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) <130 mEq/L	0 participants	0 participants	0 participants	0 participants	0 participants

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo-Period 1 n=23 participants at risk Study period 1: single dose of placebo.	Desmopressin 10µg - Period 1 n=25 participants at risk Study period 1: single dose of desmopressin 10µg.	Desmopressin 25µg - Period 1 n=22 participants at risk Study period 1: single dose of desmopressin 25µg.	Desmopressin 50µg - Period 1 n=22 participants at risk Study period 1: single dose of desmopressin 50µg.	Desmopressin 100µg - Period 1 n=24 participants at risk Study period 1: single dose of desmopressin 100µg.	Placebo - Period 2 n=23 participants at risk Study period 2: daily doses of placebo taken before bedtime for 28 days.	Desmopressin 10µg - Period 2 n=23 participants at risk Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.	Desmopressin 25µg - Period 2 n=22 participants at risk Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.	Desmopressin 50µg - Period 2 n=22 participants at risk Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.	Desmopressin 100µg - Period 2 n=23 participants at risk Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Nervous system disorders Headache	0.00% 0/23 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/25 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	4.5% 1/22 • Number of events 1 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	4.5% 1/22 • Number of events 1 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	8.3% 2/24 • Number of events 2 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/23 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/23 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	9.1% 2/22 • Number of events 2 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/22 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/23 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)
Investigations Blood sodium decreased	0.00% 0/23 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	4.0% 1/25 • Number of events 1 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/22 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	13.6% 3/22 • Number of events 3 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	20.8% 5/24 • Number of events 5 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/23 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/23 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/22 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	4.5% 1/22 • Number of events 1 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/23 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)
Infections and infestations Nasopharyngitis	0.00% 0/23 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/25 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/22 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/22 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/24 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	13.0% 3/23 • Number of events 4 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	4.3% 1/23 • Number of events 1 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	9.1% 2/22 • Number of events 2 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/22 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)	0.00% 0/23 • Period 1: Day 1 to Day 3 (includes Wash-out period) Period 2: Day 4 (first day of period 2 drug administration) to Day 32 (last day of drug administration or date of withdrawal)

Additional Information

Clinical Development Support

Ferring Pharmaceuticals

Email: [email protected]

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