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

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

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.

Study Overview

• Status: Completed
• Conditions: Nocturia
• Intervention / Treatment: Drug: Desmopressin Melt

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 554
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y-2H4
      • Southern Interior Medical Research Inc.
    • Victoria, British Columbia, Canada, V8T 5G1
      • Can-Med Clinical Research Inc.
    • Victoria, British Columbia, Canada, V8V 3N1
      • Investigational site - Clinical Research
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 5B8
      • Investigational site - Professional Corporation
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • The Male/Female Health and Research
    • Brantford, Ontario, Canada, N3R 4N3
      • Brantford Urology Research
    • Guelph, Ontario, Canada, N1H 5J1
      • Guelph Urology Associates
    • North Bay, Ontario, Canada, P1B 7K8
      • Investigational Site
    • Oakville, Ontario, Canada, L6H 3P1
      • The Fe/Male Health Centres
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Radiant Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Arkansas Primary Care Clinic, PA
  • California
    • Anaheim, California, United States, 92801
      • Advanced Urology Medical Center
    • Beverly Hills, California, United States, 90211
      • Impact Clinical Trials
    • Newport Beach, California, United States, 92660
      • California Professional Research
    • San Diego, California, United States, 92103
      • San Diego Uro-Reseach
    • Santa Rosa, California, United States, 95405
      • Radiant Research
    • Tarzana, California, United States, 91356
      • West Coast Clinical Research
    • Torrance, California, United States, 90505
      • Western Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80218
      • Downtown Women's Health Care
    • Denver, Colorado, United States, 80220
      • Genitourinary Surgical Consultants
    • Denver, Colorado, United States, 80210
      • Urology Associates PC
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Connecticut Clinical Research Center, LLC
  • Florida
    • Aventura, Florida, United States, 33180
      • South Florida Medical Research
    • Clearwater, Florida, United States, 33759
      • Women's Health Research Group, LLC
    • Pinellas Park, Florida, United States, 33781
      • Radiant Research - St. Petersburg
    • Plantation, Florida, United States, 33324
      • Sunrise Medical Research
    • Stuart, Florida, United States, 34996
      • Radiant Research
    • Tampa, Florida, United States, 33607
      • Tampa Bay Urology
    • West Palm Beach, Florida, United States, 33407
      • Radiant Research
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Southeastern Medical Research Institute
    • Dunwoody, Georgia, United States, 30338
      • Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60654
      • Radiant Research, Inc
    • Peoria, Illinois, United States, 61602
      • Accelovance
  • Kansas
    • Overland Park, Kansas, United States, 66202
      • Radiant Research, Kansas City
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Benchmark Research
    • Shreveport, Louisiana, United States, 71106
      • Regional Urology, LLC
  • Massachusetts
    • Springfield, Massachusetts, United States, 01103
      • FutureCare Studies, Inc.
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Radiant Research, Minneapolis
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • Radiant Research, Inc.
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Women's Clinic of Lincoln, P.C.
  • Nevada
    • Las Vegas, Nevada, United States
      • Sheldon J Freedman Ltd
  • New Jersey
    • Elizabeth, New Jersey, United States, 07202
      • Central Jersey Medical Research Center
    • Lawrenceville, New Jersey, United States, 08648
      • Lawrenceville Urology, P.A. DBA
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Urology Group of New Mexico, PC
  • New York
    • Carmel, New York, United States, 10512
      • Investigational site - Adult & Pediatric Urology
    • Garden City, New York, United States, 11530
      • AccuMed Research Associates
    • NY, New York, United States, 12206-1092
      • Upstate Urology
    • New York, New York, United States, 10016
      • University Urology Associates
    • Poughkeepsie, New York, United States, 12601
      • Hudson Valley Urology, PC
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Wilmington, North Carolina, United States, 28401
      • New Hanover Medical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45249
      • Radiant Research Inc.
    • Mogadore, Ohio, United States, 44260
      • Radiant Research - Akron
  • Pennsylvania
    • Bala Cynwyd, Pennsylvania, United States, 19004
      • Urologic Consultants of SE PA
    • Philadelphia, Pennsylvania, United States, 19114
      • Philadelphia Clinical Research, LLC
    • West Readings, Pennsylvania, United States, 19611
      • Advanced Clinical Concepts
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Radiant Research, Greer
    • Mt. Pleasant, South Carolina, United States, 29464
      • Palmetto Medical Research
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
  • Texas
    • Corpus Christi, Texas, United States, 78414
      • Advanced Research Associates
    • Houston, Texas, United States, 77024
      • Accelovance
    • Houston, Texas, United States, 77004
      • Investigational site - NationsMed Clinical Research
    • Humble, Texas, United States, 77338
      • Regional Medical Center and Diagnostic
    • San Antonio, Texas, United States, 78229
      • Innovative Clinical Trials
    • San Antonio, Texas, United States, 78229
      • Radiant Research San Antonio
    • San Antonio, Texas, United States, 78258
      • IMED Research, P.A.
    • Stafford, Texas, United States
      • NationsMed
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Virginia Urology
    • Virginia Beach, Virginia, United States, 23454
      • Urology of Virginia PC
  • Washington
    • Seattle, Washington, United States, 98105
      • Women's Clinical Research Center
    • Seattle, Washington, United States, 98166
      • Seattle Urology Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Desmopressin Melt 10 μg; 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; An orally disintegrating tablet of desmopressin administered under the tongue (sublingually), without water.; Other Names: FE992026; Nocturin®; Minirin® Melt
EXPERIMENTAL: Desmopressin Melt 25 μg; 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; An orally disintegrating tablet of desmopressin administered under the tongue (sublingually), without water.; Other Names: FE992026; Nocturin®; Minirin® Melt
EXPERIMENTAL: Desmopressin Melt 50 μg; 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; An orally disintegrating tablet of desmopressin administered under the tongue (sublingually), without water.; Other Names: FE992026; Nocturin®; Minirin® Melt
EXPERIMENTAL: Desmopressin Melt 100 μg; 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; An orally disintegrating tablet of desmopressin administered under the tongue (sublingually), without water.; Other Names: FE992026; Nocturin®; Minirin® Melt

What is the study measuring?

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).

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Publications and helpful links

General Publications

• Juul KV, Klein BM, Sandstrom R, Erichsen L, Norgaard JP. Gender difference in antidiuretic response to desmopressin. Am J Physiol Renal Physiol. 2011 May;300(5):F1116-22. doi: 10.1152/ajprenal.00741.2010. Epub 2011 Mar 2.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (ACTUAL): May 1, 2010
• Study Completion (ACTUAL): May 1, 2010

Study Registration Dates

• First Submitted: January 18, 2008
• First Submitted That Met QC Criteria: February 4, 2008
• First Posted (ESTIMATE): February 14, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): December 15, 2015
• Last Update Submitted That Met QC Criteria: November 11, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lower Urinary Tract Symptoms; Urological Manifestations; Nocturia; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Antidiuretic Agents; Deamino Arginine Vasopressin
• Other Study ID Numbers: FE992026 CS31