An Extension Study Investigating the Efficacy and Safety of a Fast-Dissolving (Melt) Formulation of Desmopressin for the Treatment of Nocturia in Adults

Study Overview
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Brief Summary
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The purpose of this study was to investigate the long term efficacy and safety of several doses of the Melt formulation of desmopressin in a broad population of adult patients with nocturia.

Detailed Description
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FE992026 CS31 was a multicenter open-label extension study for patients who were enrolled in Study FE992026 CS29 (NCT00477490) and had completed at least Visit 3E in Part II of that study. The CS29 study was structured into 2 double-blind parts (Part I and Part II). In Part I, the initial 28-day treatment period, participants were randomly assigned to 1 of 5 treatment groups: placebo or desmopressin Melt 10 μg, 25 μg, 50 μg, or 100 μg. Immediately upon completion of Part I of the study, all participants on active treatment continued into Part II on the same treatment for approximately 1 to 6 months. Participants assigned to placebo in Part I were randomly assigned to 1 of the 4 active treatments in Part II, based on re-randomization predetermined at the initial randomization (to maintain the blind). Part II began at the final visit for Part I and continued until the database for Part I was locked. Therefore, treatment duration for Part II varied between 1 and 6 months, depending upon when the participant entered. Upon completion of Part II of CS29, participants were given the option to participate in the open-label extension study (CS31). During CS31, each participant assigned to the 10 μg dose was switched to a higher dose in an open-label manner among the remaining 3 higher doses.

Official Title
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A Multi-Center Extension Study Investigating the Long Term Efficacy and Safety of a Fast-Dissolving (Melt) Formulation of Desmopressin for the Treatment of Nocturia in Adults

Conditions
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Nocturia

Intervention / Treatment
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* Drug: Desmopressin Melt


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent prior to the performance of any study-related activity. Was randomized into Part II of Protocol FE992026 CS29 (NCT00477490), entitled A Randomized, Double Blind,Placebo Controlled, Parallel Group, Multi-Center Study with a Double Blind Extension Investigating the Efficacy and Safety of a Fast-Dissolving (Melt) Formulation of Desmopressin for the Treatment of Nocturia in Adults and have completed at least Visit 3E in Part II (Day 15). Exclusion Criteria: Patients using loop diuretics (furosemide, torsemide, ethacrynic acid).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Desmopressin Melt 10 μg<br>Participants received desmopressin melt 10 μg once a day, placed under the tongue one hour before bedtime until they were re-randomized to one of the other doses of desmopressin Melt (25 μg, 50 μg, or 100 μg). | Drug: Desmopressin Melt<br>* An orally disintegrating tablet of desmopressin administered under the tongue (sublingually), without water.<br>* Other names: FE992026;|
| Experimental: Desmopressin Melt 25 μg<br>Participants received desmopressin melt 25 μg once a day, placed under the tongue one hour before bedtime for up to 2 years and 2.5 months. | Drug: Desmopressin Melt<br>* An orally disintegrating tablet of desmopressin administered under the tongue (sublingually), without water.<br>* Other names: FE992026;|
| Experimental: Desmopressin Melt 50 μg<br>Participants received desmopressin melt 50 μg once a day, placed under the tongue one hour before bedtime for up to 2 years and 2.5 months. | Drug: Desmopressin Melt<br>* An orally disintegrating tablet of desmopressin administered under the tongue (sublingually), without water.<br>* Other names: FE992026;|
| Experimental: Desmopressin Melt 100 μg<br>Participants received desmopressin melt 100 μg once a day, placed under the tongue one hour before bedtime for up to 2 years and 2.5 months. | Drug: Desmopressin Melt<br>* An orally disintegrating tablet of desmopressin administered under the tongue (sublingually), without water.<br>* Other names: FE992026;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Number of Nocturnal Voids | Participants completed a voiding diary for 3 consecutive 24-hour periods prior to the study visit in which they recorded each nocturnal urination (void). The mean number of voids per night was the average number of voids from the 3-day diary. Baseline refers to Baseline of Study CS29 and the number of weeks represents the total exposure to study drug. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29 and Weeks 8, 12, 20, 28, 52-56, 72-76, and 92-96. | 
| Percentage of Participants With a Greater Than 33% Reduction in the Mean Number of Nocturnal Voids | Percentage of participants with >33% reduction from Baseline in the mean number of nocturnal urinations per night, calculated from the 3-day voiding diary completed prior to each study visit. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29 and Weeks 8, 12, 20, 28, 52-56, 72-76, and 92-96. | 
| Change From Baseline in Initial Period of Undisturbed Sleep | Participants completed a sleep diary on 3 consecutive mornings prior to each study visit, from which the initial period of undisturbed sleep was calculated and averaged for the 3 days. The Initial Period of Undisturbed Sleep is the time elapsed from bedtime to either first void or morning arising minus the minutes it took to fall asleep. Baseline refers to Baseline of Study CS29 and the number of weeks represents the total exposure to study drug. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29 and Weeks 8, 12, 20, 28, 52-56, 72-76, and 92-96. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Sleep Time | Participants completed a sleep diary on 3 consecutive mornings prior to each study visit, from which the total sleep time was calculated and averaged for the 3 days. Baseline refers to Baseline of Study CS29 and the number of weeks represents the total exposure to study drug. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29 and Weeks 8, 12, 20, 28, 52-56, 72-76, and 92-96. | 
| Change From Baseline in International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) Nighttime Urination Bother Score | The ICIQ-N is a self-administered 4-item questionnaire designed to assess the frequency and bother of daytime and nighttime urination. To assess nighttime urination bother, participants were asked to rate the degree of bother of nighttime urination by answering the question Night time urination: How much does this bother you? on a scale ranging from 0 (not at all) to 10 (a great deal). Higher numbers indicate greater bother. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months) | 
| Change From Baseline in Nocturia Quality of Life (NQoL) Overall Score | The NQoL is a self-administered 13-item questionnaire designed to assess the impact of nocturia on quality of life. It contains a sleep/energy domain (6 questions), a bother/concern domain (6 questions), and 1 global QoL question (which is not included in the overall score). The 12 core items are scored on a 0 to 4 scale, and the overall score is calculated by transforming the raw score into a 0-100 scale with higher numbers indicating better impact on quality of life. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months) | 
| Change From Baseline in NQoL Bother/Concern Domain Score | The NQoL is a self-administered 13-item questionnaire designed to assess the impact of nocturia on quality of life. It contains a sleep/energy domain (6 questions), a bother/concern domain (6 questions), and 1 global QoL question. The 12 core items are scored on a 0 to 4 scale with higher numbers indicating a better quality of life. The bother/concern domain summary score is calculated by transforming the raw score into a 0-100 scale with higher numbers indicating a better impact on quality of life. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months) | 
| Change From Baseline in Nocturia Quality of Life (NQoL) Sleep/Energy Domain Score | The NQoL is a self-administered 13-item questionnaire designed to assess the impact of nocturia on quality of life. It contains a sleep/energy domain (6 questions), a bother/concern domain (6 questions), and 1 global QoL question. The 12 core items are scored on a 0 to 4 scale with higher numbers indicating a better quality of life. The sleep/energy domain summary score is calculated by transforming the raw score into a 0-100 scale with higher numbers indicating a better impact on quality of life. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months) | 
| Change From Baseline in the Nocturia Quality of Life (NQoL) Global Quality of Life Score | The NQoL is a self-administered 13-item questionnaire designed to assess the impact of nocturia on quality of life. It contains a sleep/energy domain (6 questions), a bother/concern domain (6 questions), and 1 global QoL question. The global QoL question is scored on a scale ranging from 0 (not at all) to 10 (a great deal). Higher numbers indicate better impact on quality of life. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months) | 
| Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Global Score | The PSQI is a self-administered 19-item questionnaire designed to assess sleep quality and disturbances. The 19 individual items are scored on an evenly weighted 0 to 3 scale and generate 7 component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score ranging from 0 to 21. Higher numbers indicate greater sleep disturbance. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months) | 
| Change From Baseline in the Short Form-12, Version 2 (SF-12v2) Mental Component Summary Score | The SF-12v2 was used to measure the impact of nocturia and lack of sleep on general quality of life. The SF-12 consists of 12 questions spanning 8 domains: physical functioning, role function-physical, role function-emotional, bodily pain, general health, vitality, social functioning, and mental health. These scales are combined to create 2 summary measures: the Physical Health Summary and Mental Health Summary. The Mental Health Summary score ranges from 0 to 100, where higher numbers indicate better quality of life. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months) | 
| Change From Baseline in the Short Form-12, Version 2 (SF-12v2) Physical Component Summary Score | The SF-12v2 was used to measure the impact of nocturia and lack of sleep on general quality of life. The SF-12 consists of 12 questions spanning 8 domains: physical functioning, role function-physical, role function-emotional, bodily pain, general health, vitality, social functioning, and mental health. These scales are combined to create 2 summary measures: the Physical Health Summary and Mental Health Summary. The Physical Health Summary score ranges from 0 to 100, where higher numbers indicate better quality of life. Participants in the 10μg arm are included only until the time of dose escalation. | Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months) | 
| Participants With Treatment-Emergent Adverse Events (AEs) | An AE was any untoward medical occurrence that did not necessarily have a causal relationship with the study drug. An adverse drug reaction (ADR) was an AE evaluated by the Investigator as being probably or possibly causally related to treatment with the study drug. A serious AE (SAE) was any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or congenital anomaly/birth defect or was an important medical event that could have jeopardized the patient's safety or required medical or surgical intervention to prevent 1 of the outcomes listed above. The intensity of an AE was defined as severe if it resulted in the inability to work or perform usual activities. | From first dose of study drug in Study CS29 until the end of study CS31 (up to 35 months). |