Trial Outcomes & Findings for Investigation of the Superiority Effect of Orally Disintegrating Desmopressin Tablets to Placebo in Terms of Night Voids Reduction in Nocturia Adult Male Patients (NCT NCT01262456)

NCT ID: NCT01262456

Last Updated: 2015-10-15

Results Overview

The number of nocturnal voids was the average over 3 consecutive 24-hour periods prior to Day 1 and prior to the during-treatment visits (Week 1, Months 1, 2, 3) as recorded in participant diaries. The first morning void was not counted as a nocturnal void. Change from baseline values for Week 1, and Months 1, 2 and 3 are reported below. Comparison of the mean number of nocturnal voids at baseline and over a 3-month treatment period (obtained by longitudinal analysis of Week 1, and Months 1, 2 and 3) are reported in the statistical analysis. This was the first co-primary outcome. Superiority to placebo was to be simultaneously demonstrated on the 2 co-primary outcomes in a step-down approach from highest (75 μg) to lowest dose (50 μg), thereby controlling the family-wise error rate at the 5% nominal significance level.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 395 participants
• Primary outcome timeframe: Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind treatment period)
• Results posted on: 2015-10-15

Participant Flow

A total of 1013 participants were screened; 618 were screening failures and 395 were randomized. The most common reason for screening failure was non-fulfillment of inclusion/exclusion criteria (535 participants); 23 participants withdrew consent prior to randomization and 60 participants had other reasons for screening failure.

Participant milestones

Measure	Placebo Double-Blind / Desmopressin 100 μg Open-Label Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for the 1-month open-label extension period.	50 μg Double-Blind / 100 μg Open-Label Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for the 1-month open-label extension period.	Desmopressin 75 μg Double-Blind / 100 μg Open-Label Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for the 1-month open-label extension period.
3-Month Double-Blind Period STARTED	143	123	129
3-Month Double-Blind Period Full Analysis Set (FAS)	142	119	124
3-Month Double-Blind Period Safety Analysis Set (SAS)	143	119	122
3-Month Double-Blind Period COMPLETED	124	100	103
3-Month Double-Blind Period NOT COMPLETED	19	23	26
1-Month Open-Label Extension Period STARTED	124	100	103
1-Month Open-Label Extension Period Safety Analysis Set (SAS)	124	101	102
1-Month Open-Label Extension Period COMPLETED	120	97	98
1-Month Open-Label Extension Period NOT COMPLETED	4	3	5

Reasons for withdrawal

Measure	Placebo Double-Blind / Desmopressin 100 μg Open-Label Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for the 1-month open-label extension period.	50 μg Double-Blind / 100 μg Open-Label Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for the 1-month open-label extension period.	Desmopressin 75 μg Double-Blind / 100 μg Open-Label Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for the 1-month open-label extension period.
3-Month Double-Blind Period Withdrawal by Subject	6	8	9
3-Month Double-Blind Period Lost to Follow-up	4	5	3
3-Month Double-Blind Period Adverse Event	6	4	8
3-Month Double-Blind Period Protocol Violation	3	6	6
1-Month Open-Label Extension Period Withdrawal by Subject	1	1	1
1-Month Open-Label Extension Period Lost to Follow-up	0	1	0
1-Month Open-Label Extension Period Adverse Event	2	0	2
1-Month Open-Label Extension Period Protocol Violation	1	0	2
1-Month Open-Label Extension Period Other Reason	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo Double-Blind n=142 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=119 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 75 μg Double-Blind n=124 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Total n=385 Participants Total of all reporting groups
Age, Continuous	60.8 years STANDARD_DEVIATION 14.2 • n=5 Participants	60.8 years STANDARD_DEVIATION 13.2 • n=7 Participants	60.1 years STANDARD_DEVIATION 11.6 • n=5 Participants	60.6 years STANDARD_DEVIATION 13.1 • n=4 Participants
Age, Customized <65 years	74 participants n=5 Participants	62 participants n=7 Participants	64 participants n=5 Participants	200 participants n=4 Participants
Age, Customized >=65 years	68 participants n=5 Participants	57 participants n=7 Participants	60 participants n=5 Participants	185 participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	142 Participants n=5 Participants	119 Participants n=7 Participants	124 Participants n=5 Participants	385 Participants n=4 Participants
Race/Ethnicity, Customized White	112 participants n=5 Participants	99 participants n=7 Participants	99 participants n=5 Participants	310 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	27 participants n=5 Participants	18 participants n=7 Participants	22 participants n=5 Participants	67 participants n=4 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	7 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	20 participants n=5 Participants	25 participants n=7 Participants	29 participants n=5 Participants	74 participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	122 participants n=5 Participants	94 participants n=7 Participants	95 participants n=5 Participants	311 participants n=4 Participants
Body Mass Index (BMI)	29.2 kg/m^2 STANDARD_DEVIATION 5.25 • n=5 Participants	29.3 kg/m^2 STANDARD_DEVIATION 4.77 • n=7 Participants	29.2 kg/m^2 STANDARD_DEVIATION 4.79 • n=5 Participants	29.2 kg/m^2 STANDARD_DEVIATION 4.95 • n=4 Participants

PRIMARY outcome

Timeframe: Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind treatment period)

Population: Full analysis set (FAS).

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

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

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=124 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=119 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=142 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period Week 1 (n=120, 116, 141)	-1.06 nocturnal voids Standard Deviation 1.9	-0.973 nocturnal voids Standard Deviation 0.898	-0.591 nocturnal voids Standard Deviation 1.05
Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period Month 1 (n=117, 112, 139)	-1.4 nocturnal voids Standard Deviation 1.01	-1.31 nocturnal voids Standard Deviation 1.01	-0.928 nocturnal voids Standard Deviation 1.96
Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period Month 2 (n=113, 107, 132)	-1.43 nocturnal voids Standard Deviation 1.04	-1.4 nocturnal voids Standard Deviation 1.04	-1.01 nocturnal voids Standard Deviation 1.14
Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period Month 3 (n=106, 103, 125)	-1.37 nocturnal voids Standard Deviation 1.13	-1.25 nocturnal voids Standard Deviation 1.01	-0.984 nocturnal voids Standard Deviation 1.04

PRIMARY outcome

Timeframe: Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind treatment period)

Population: Full analysis set (FAS).

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

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

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=124 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=119 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=142 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Adjusted Probability of Participants Achieving a >33% Reduction From Baseline in Number of Nocturnal Voids for All During-Treatment Visits up to Month 3	0.67 probability	0.67 probability	0.50 probability

SECONDARY outcome

Timeframe: Day 1 (Baseline), Month 3

Population: Full Analysis Set (FAS), including participants with complete data supporting this outcome in the participant diary.

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

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

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=106 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=103 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=125 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Change From Baseline in Mean Number of Nocturnal Voids at Month 3	-1.37 nocturnal voids Standard Deviation 1.13	-1.25 nocturnal voids Standard Deviation 1.01	-0.984 nocturnal voids Standard Deviation 1.04

SECONDARY outcome

Timeframe: Day 1 (Baseline), Month 3

Population: FAS, including participants with complete data supporting this outcome in the participant diary.

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

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

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=106 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=103 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=125 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Adjusted Probability of Participants Achieving a >33% Reduction From Baseline in Number of Nocturnal Voids at Month 3	0.68 probability	0.66 probability	0.54 probability

SECONDARY outcome

Timeframe: Day 1 (Baseline), Month 3

Population: FAS, including participants with complete data supporting this outcome in the participant diary.

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

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

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=106 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=103 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=125 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Change From Baseline in Mean Time to First Nocturnal Void at Month 3	117 minutes Standard Deviation 130	113 minutes Standard Deviation 119	71.5 minutes Standard Deviation 108

SECONDARY outcome

Timeframe: Day 1 (Baseline), Month 3

Population: FAS, including participants with complete data supporting this outcome in the participant diary.

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

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

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=103 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=102 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=124 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Change From Baseline in Nocturnal Urine Volume at Month 3	-199 mL Standard Deviation 274	-186 mL Standard Deviation 263	-144 mL Standard Deviation 260

SECONDARY outcome

Timeframe: Day 1 (Baseline), Month 3

Population: FAS, including participants with complete data supporting this outcome in the participant diary.

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

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

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=101 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=102 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=119 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Change From Baseline in 24-Hour Urine Volume at Month 3	-224 mL Standard Deviation 549	-194 mL Standard Deviation 491	-197 mL Standard Deviation 442

SECONDARY outcome

Timeframe: From Day 1 through Month 3 (double-blind period)

Population: Safety analysis set (SAS)

A TEAE was any adverse event (AE) occurring after start of treatment and within the time of residual drug effect, i.e., within 1 day for desmopressin. An adverse drug reaction (ADR) was any AE assessed by the investigator as possibly or probably related to study drug.

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=143 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=119 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=122 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Period All AEs	58 participants	46 participants	49 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Period AEs leading to discontinuation	7 participants	4 participants	7 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Period Serious AEs (SAEs)	1 participants	4 participants	5 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Period Severe AEs	2 participants	2 participants	2 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Period Adverse drug reactions (ADRs)	22 participants	23 participants	20 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Period ADRs leading to discontinuation	4 participants	4 participants	5 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Period Deaths	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Month 1 of open-label period (Month 4 of treatment)

Population: Safety analysis set (SAS) for open label-treatment period

A TEAE was any adverse event (AE) occurring after start of treatment and within the time of residual drug effect, i.e., within 1 day for desmopressin. An adverse drug reaction (ADR) was any AE assessed by the investigator as possibly or probably related to study drug.

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=124 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=101 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=102 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Period Serious AEs (SAEs)	2 participants	0 participants	1 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Period All AEs	26 participants	23 participants	23 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Period Severe AEs	0 participants	0 participants	1 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Period Adverse drug reactions (ADRs)	9 participants	6 participants	9 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Period AEs leading to discontinuation	2 participants	0 participants	2 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Period ADRs leading to discontinuation	2 participants	0 participants	2 participants
Summary of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Period Deaths	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 through Month 3 (double-blind period)

Population: Safety analysis set (SAS)

Serum sodium levels were monitored at each study visit since hyponatremia is a potential serious adverse event associated with daily doses of desmopressin. The serum sodium level must have been within the normal reference range at the Screening Visit for the participant to be eligible for enrollment. A participant was to be withdrawn from the trial if the serum sodium level was <=125 mmol/L at any time.

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=143 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=119 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=122 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Minimum Post-Treatment Serum Sodium Levels in the Double-Blind Period ≤125 mmol/L	0 participants	2 participants	4 participants
Minimum Post-Treatment Serum Sodium Levels in the Double-Blind Period 126-129 mmol/L	0 participants	0 participants	5 participants
Minimum Post-Treatment Serum Sodium Levels in the Double-Blind Period 130-134 mmol/L	2 participants	9 participants	12 participants
Minimum Post-Treatment Serum Sodium Levels in the Double-Blind Period ≥135 mmol/L	141 participants	108 participants	101 participants

SECONDARY outcome

Timeframe: Month 1 of open-label period (Month 4 of treatment)

Population: Safety analysis set (SAS) during open-label treatment period

Serum sodium levels were monitored at each study visit since hyponatremia is a potential serious adverse event associated with daily doses of desmopressin. The serum sodium level must have been within the normal reference range at the Screening Visit for the participant to be eligible for enrollment. A participant was to be withdrawn from the trial if the serum sodium level was <=125 mmol/L at any time.

Outcome measures

Measure	Desmopressin 75 μg Double-Blind n=124 Participants Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind n=101 Participants Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=102 Participants Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.
Minimum Post-Treatment Serum Sodium Levels in the Open-Label Period 130-134 mmol/L	10 participants	12 participants	11 participants
Minimum Post-Treatment Serum Sodium Levels in the Open-Label Period ≥135 mmol/L	110 participants	88 participants	89 participants
Minimum Post-Treatment Serum Sodium Levels in the Open-Label Period ≤125 mmol/L	1 participants	0 participants	1 participants
Minimum Post-Treatment Serum Sodium Levels in the Open-Label Period 126-129 mmol/L	3 participants	1 participants	1 participants

Adverse Events

Desmopressin 50 μg Double-Blind

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Desmopressin 75 μg Double-Blind

Serious events: 5 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo Double-Blind

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Desmopressin 50 μg Double-Blind / 100 μg Open-Label

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Desmopressin 75 μg Double-Blind / 100 μg Open-Label

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo Double-Blind / Desmopressin 100 μg Open-Label

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Desmopressin 50 μg Double-Blind n=119 participants at risk Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 75 μg Double-Blind n=122 participants at risk Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=143 participants at risk Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind / 100 μg Open-Label n=101 participants at risk Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.	Desmopressin 75 μg Double-Blind / 100 μg Open-Label n=102 participants at risk Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.	Placebo Double-Blind / Desmopressin 100 μg Open-Label n=124 participants at risk Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.
Cardiac disorders Acute myocardial infarction	0.84% 1/119 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/122 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/143 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/101 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/102 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/124 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period
General disorders Pyrexia	0.00% 0/119 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/122 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.70% 1/143 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/101 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/102 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/124 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period
Metabolism and nutrition disorders Hyponatraemia	1.7% 2/119 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	3.3% 4/122 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/143 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/101 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.98% 1/102 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.81% 1/124 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period
Musculoskeletal and connective tissue disorders Osteoarthritis	0.84% 1/119 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/122 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/143 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/101 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/102 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/124 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period
Nervous system disorders Transient global amnesia	0.00% 0/119 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.82% 1/122 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/143 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/101 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/102 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/124 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period
Injury, poisoning and procedural complications Rib fracture	0.00% 0/119 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/122 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/143 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/101 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/102 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.81% 1/124 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period

Other adverse events

Measure	Desmopressin 50 μg Double-Blind n=119 participants at risk Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 75 μg Double-Blind n=122 participants at risk Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Placebo Double-Blind n=143 participants at risk Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period.	Desmopressin 50 μg Double-Blind / 100 μg Open-Label n=101 participants at risk Participants took 1 orally disintegrating tablet of desmopressin 50 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.	Desmopressin 75 μg Double-Blind / 100 μg Open-Label n=102 participants at risk Participants took 1 orally disintegrating tablet of desmopressin 75 μg every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.	Placebo Double-Blind / Desmopressin 100 μg Open-Label n=124 participants at risk Participants took 1 orally disintegrating tablet of placebo every night approximately 1 hour prior to bedtime for the entire duration of the 3-month double-blind treatment period. Participants were switched to desmopressin 100 μg for 1-month open-label extension period.
Nervous system disorders Headache	5.0% 6/119 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	5.7% 7/122 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	3.5% 5/143 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/101 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.00% 0/102 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period	0.81% 1/124 • Day 1 through Month 3 for double-blind period; Month 4 for open-label period

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