Efficacy and Safety of Desmopressin Melt for the Treatment of Nocturia
29 septembre 2015 mis à jour par: Ferring Pharmaceuticals
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
The purpose of this study is to investigate the efficacy and safety of several doses of the melt formulation of desmopressin in a broad population of adult patients with nocturia.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
799
Phase
- Phase 3
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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British Columbia
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Kelowna, British Columbia, Canada, V1Y-2H4
- Southern Interior Medical Center
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Victoria, British Columbia, Canada, V8T 5G1
- Can-Med Clinical Research Inc.
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Victoria, British Columbia, Canada, V8V 3N1
- Investigational site - Clinical Research
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New Brunswick
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Fredericton, New Brunswick, Canada, E3B 5B8
- Investigational site - Professional Corporation
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Ontario
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Barrie, Ontario, Canada, L4M 7G1
- The Male/Female Health and Reserach
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Brantford, Ontario, Canada, N3R 4N3
- Brantford Urology Research
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Guelph, Ontario, Canada, N1H 5J1
- Guelph Urology Associates
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North Bay, Ontario, Canada, P1B 4Z2
- Investigational Site
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Oakville, Ontario, Canada, L6H 3P1
- The Fe/Male Health Centres
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Toronto, Ontario, Canada, M4N 3M5
- Sunnybrook Health Sciences Centre
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Alabama
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Birmingham, Alabama, États-Unis, 35209
- Radiant Research
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Arizona
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Scottsdale, Arizona, États-Unis, 85251
- Radiant Research
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Arkansas
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Little Rock, Arkansas, États-Unis, 72204
- Arkansas Primary Care Clinic
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California
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Anaheim, California, États-Unis, 92801
- Advanced Urology Medical Center
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Beverly Hills, California, États-Unis, 90211
- Impact Clinical Trials
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Long Beach, California, États-Unis, 90806
- Atlantic Urology Medical Group
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Newport Beach, California, États-Unis, 92660
- California Professional Research
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San Diego, California, États-Unis, 92103
- San Diego Uro-Research
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Santa Rosa, California, États-Unis, 95404
- Radiant Research
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Tarzana, California, États-Unis, 91356
- West Coast Clinical Research
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Torrance, California, États-Unis, 90505
- Western Clinical Research
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Colorado
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Denver, Colorado, États-Unis, 80218
- Downtown Women's Health Care
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Denver, Colorado, États-Unis, 80220
- Genitourinary Surgical Consultants
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Denver, Colorado, États-Unis, 80210
- Urology Associates PC
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Connecticut
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Middlebury, Connecticut, États-Unis, 06762
- Connecticut Clinical Research Center, LLC
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Florida
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Aventura, Florida, États-Unis, 33180
- South Florida Medical Research
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Clearwater, Florida, États-Unis, 33759
- Women's Medical Research Group, LLC
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Miami, Florida, États-Unis, 33145
- Medsearch Professional Group
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Plantation, Florida, États-Unis, 33324
- Sunrise Medical Research
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Stuart, Florida, États-Unis, 34996
- Radiant Research
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Tallahassee, Florida, États-Unis, 32308
- Southeastern Research Group, Inc.
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Tampa, Florida, États-Unis, 33607
- Tampa Bay Urology
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West Palm Beach, Florida, États-Unis, 33407
- Radiant Research
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Georgia
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Columbus, Georgia, États-Unis, 31904
- Southeastern Medical Research Institute
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Dunwoody, Georgia, États-Unis, 30338
- Investigational site - PC
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Illinois
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Peoria, Illinois, États-Unis, 61602
- Accelovance
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Kansas
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Overland park, Kansas, États-Unis, 66202
- Radiant Research, Kansas City
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Louisiana
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Metairie, Louisiana, États-Unis, 70006
- Benchmark Research
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Shreveport, Louisiana, États-Unis, 71106
- Regional Urology, LLC
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Shreveport, Louisiana, États-Unis, 71111
- Pierremont Women's Clinic
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Massachusetts
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Springfield, Massachusetts, États-Unis, 01103
- FutureCare Studies, Inc.
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Missouri
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St. Louis, Missouri, États-Unis, 63141
- Radiant Research Inc.
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Nebraska
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Lincoln, Nebraska, États-Unis, 68510
- Women's Clinic of Lincoln, P.C
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Nevada
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Las Vegas, Nevada, États-Unis, 89109
- Investigational Site
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New Jersey
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Lawrenceville, New Jersey, États-Unis, 08648
- Lawrenceville Urology
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Lawrenceville, New Jersey, États-Unis, 08648
- AdvanceMed Research
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Morristown, New Jersey, États-Unis, 07960
- Morristown Urology
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New Mexico
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Albuquerque, New Mexico, États-Unis, 87109
- Urology Group of New Mexico, PC
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New York
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Albany, New York, États-Unis, 12206
- Upstate Urology
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Carmel, New York, États-Unis, 10512
- Investigational site - Adult & Pediatric Urology
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Garden City, New York, États-Unis, 11530
- AccuMed Research Associates
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New York, New York, États-Unis, 10016
- University Urology Associates
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Suffern, New York, États-Unis, 10901
- Ferring Pharmaceutical Inc
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North Carolina
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Concord, North Carolina, États-Unis, 28025
- Northeast Urology Research
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Greensboro, North Carolina, États-Unis, 27401
- PharmQuest
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Wilmington, North Carolina, États-Unis, 28401
- New Hanover Medical Research
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Winston-Salem, North Carolina, États-Unis, 27103
- Piedmont Medical Research Associates
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Ohio
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Cincinnati, Ohio, États-Unis, 45249
- Radiant Research
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Mogadore, Ohio, États-Unis, 44260
- Radiant Research - Akron
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Pennsylvania
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Bala Cynwyd, Pennsylvania, États-Unis, 19004
- Urologic Consultants of SE PA
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Philadelphia, Pennsylvania, États-Unis, 19115
- Radiant Research
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Philadelphia, Pennsylvania, États-Unis, 19114
- Philadelphia Clinical Research, LLC
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Reading, Pennsylvania, États-Unis, 19611
- Advanced Clinical Concepts
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South Carolina
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Greenville, South Carolina, États-Unis, 29605
- University Medical Group
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Greer, South Carolina, États-Unis, 29651
- Radiant Research, Greer
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Mt. Pleasant, South Carolina, États-Unis, 29464
- Palmetto Medical Research
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Myrtle Beach, South Carolina, États-Unis, 29572
- Carolina Urologic Research Center
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Tennessee
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Kingsport, Tennessee, États-Unis, 37660
- Holston Medical Group
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Nashville, Tennessee, États-Unis, 37232
- Vanderbilt University Medical Center
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Texas
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Corpus Christi, Texas, États-Unis, 78414
- Advanced Research Associates
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Dallas, Texas, États-Unis, 75231
- Health Central Women's Care
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Houston, Texas, États-Unis, 77024
- Accelovance
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Humble, Texas, États-Unis, 77338
- Regional Medical Center and Diagnostic
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San Antonio, Texas, États-Unis, 78229
- Urology San Antonio Research, PA
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San Antonio, Texas, États-Unis, 78228
- Radiant Research San Antonio
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Virginia
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Richmond, Virginia, États-Unis, 23235
- Virginia Urology Center
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Virginia Beach, Virginia, États-Unis, 23454
- Urology of Virginia PC
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Washington
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Seattle, Washington, États-Unis, 98105
- Women's Clinical Research Center
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Seattle, Washington, États-Unis, 98166
- Seattle Urology Research Center
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Seattle, Washington, États-Unis, 98166
- Investigational site - Medical Professional
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria
- Written informed consent prior to the performance of any study-related activity.
- Patients 18 years and older with an average of ≥ 2 nocturnal voids per night as determined by a 3 day frequency-volume chart during the screening period.
Exclusion Criteria:
Males:
- Clinical suspicion of bladder outlet obstruction and/or urine flow < 5 ml/s. If medical history and/or physical examination suggest bladder outlet obstruction, uroflowmetry should be performed to confirm the diagnosis
Surgical treatment for bladder outlet obstruction/benign prostatic hyperplasia performed within the past 6 months
Females:
- Pregnancy. Females of reproductive age must have documentation of a reliable method of contraception.
- Use of pessary for pelvic prolapse.
Unexplained pelvic mass.
Males and Females:
- Clinical suspicion of urinary retention and/or post void residual volume > 150 ml. If medical history and/or physical examination suggest urinary retention, bladder ultrasound or catheterization should be performed to confirm the diagnosis.
- Current or past urologic malignancy (e.g., bladder cancer, prostate cancer).
- Clinical evidence of current genitourinary tract pathology that could interfere with voiding.
- History of neurogenic detrusor activity (previously known as detrusor hyperreflexia).
- Suspicion or evidence of cardiac failure.
- Uncontrolled hypertension.
- Uncontrolled diabetes mellitus.
- Renal insufficiency. Serum creatinine must be within normal limits and estimated glomerular filtration rate (eGFR) >=60 mL/min.
- Active hepatic and/or biliary disease. Aspartate transaminase (AST) or alanine transaminase (ALT) should not be >2 times the upper limit of normal. Total bilirubin should not be > 1.5 mg/dL.
- Hyponatremia. Serum sodium level must be within normal limits
- Syndrome of Inappropriate antidiuretic hormone secretion (SIADH).
- Diabetes insipidus (urine output > 40 ml/kg over 24 hours) as determined by the 3-day voiding diary.
- Psychogenic or habitual polydipsia
Obstructive sleep apnea
Other
- Known alcohol or substance abuse
- Work or lifestyle potentially interfering with regular nighttime sleep (e.g., shift workers)
- Previous desmopressin treatment for nocturia.
- Any other medical condition, laboratory abnormality, psychiatric condition, mental incapacity or language barrier that, in the judgment of the investigator, could impair patient participation in the trial.
- Use of loop diuretics (furosemide, torsemide, ethacrynic acid). Other classes of diuretics (thiazides, triamterene, chlorthalidone, amiloride, indapamide) were permitted, either as monotherapy or combination therapy. Subjects using a diuretic were to be encouraged to take it in the morning, if medically feasible.
- Use of any other investigational drug within 30 days of screening.
Concomitant Medications
The following medications are permitted provided that the subject has been on a stable dose for the 3 months prior to the screening date (i.e. treatment has not been initiated or discontinued and there has been no change in dose):
- Alpha-blockers: Cardura (doxazosin); Flomax (tamsulosin); Hytrin (terazosin); Uroxatral (alfuzosin)
- 5 alpha-reductase inhibitors: Avodart (dutasteride); Proscar (finasteride)
- Antispasmodic, anticholinergic, antimuscarinic therapy for overactive bladder: Detrol, Detrol LA (tolterodine); Ditropan, Ditropan XL (oxybutynin); Enablex (darifenacin); Levsin(hyoscyamine); Oxytrol transdermal (oxybutynin); Sanctura (trospium); Vesicare (solifenacin)
- Sedative/hypnotic medications for sleep disorders
- Selective serotonin and mixed norepinephrine/serotonin reuptake inhibitors: Celexa (citalopram); Cymbalta (duloxetine); Effexor (venlafaxine); Lexapro (escitalopram); Paxil(paroxetine); Prozac (fluoxetine); Zoloft (sertraline)
- Chronic use of nonsteroidal anti-inflammatory agents
- Diabinese (chlorpropamide)
- Carbamazepine (carbatrol/tegretol)
- Amiodarone
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Comparateur placebo: Placebo
Participants took a placebo 'melt' for 28 days to complete part 1 of the study.
In part 2, placebo patients were randomized to one of the other 4 treatment arms based on assignments predetermined at the initial randomization, to receive active desmopressin melt for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).
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Oral placebo placed under the participant's tongue, without water, once daily approximately 1 hour before bedtime.
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Expérimental: desmopressin melt 10 μg
Participants took desmopressin melt 10 μg for 28 days to complete part 1 of the study.
Participants continued on this dose in part 2 of the study for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).
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Oral lyophilisate of desmopressin acetate placed under the participant's tongue, without water, once daily approximately 1 hour before bedtime in the assigned dosage: 10, 25, 50 or 100 μg
Autres noms:
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Expérimental: desmopressin melt 25 μg
Participants took desmopressin melt 25 μg for 28 days to complete part 1 of the study.
Participants continued on this dose in part 2 of the study for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).
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Oral lyophilisate of desmopressin acetate placed under the participant's tongue, without water, once daily approximately 1 hour before bedtime in the assigned dosage: 10, 25, 50 or 100 μg
Autres noms:
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Expérimental: desmopressin melt 50 μg
Participants took desmopressin melt 50 μg for 28 days to complete part 1 of the study.
Participants continued on this dose in part 2 of the study for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).
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Oral lyophilisate of desmopressin acetate placed under the participant's tongue, without water, once daily approximately 1 hour before bedtime in the assigned dosage: 10, 25, 50 or 100 μg
Autres noms:
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Expérimental: desmopressin melt 100 μg
Participants will take desmopressin melt 100 μg for 28 days to complete part 1 of the study.
Participants will continue on this dose in part 2 of the study for between 1-6 months (until the database for part 1 is locked and treatment is unblinded).
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Oral lyophilisate of desmopressin acetate placed under the participant's tongue, without water, once daily approximately 1 hour before bedtime in the assigned dosage: 10, 25, 50 or 100 μg
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4
Délai: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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The number of nocturnal voids was the average over 3 consecutive 24-hours periods prior to Day 1 and prior to the week 4 visit as recorded in participant diaries. This was the first co-primary outcome. |
- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4
Délai: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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Percentage of participants in each treatment arm that had a greater than 33% reduction from baseline to the end of Part I (week 4) in mean number of nocturnal voids. Nocturnal void data were recorded in participant diaries. This was the second co-primary outcome. |
- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169
Délai: - Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169
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Part II outcomes tested the durability of the effect observed in Part I.
The number of nocturnal voids was the average over 3 consecutive 24-hours periods prior to Part I baseline and prior to the Part II visit as recorded in participant diaries.
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- Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169
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Part II: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169
Délai: - Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169
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Part II outcomes tested the durability of the effect observed in Part I. Percentage of participants in each treatment arm that had a greater than 33% reduction from baseline to Days 29, 57, 113 and 169 in mean number of nocturnal voids.
Nocturnal void data were recorded in participant diaries.
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- Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169
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Part I: Change From Baseline in Total Reported Sleep Time at Week 4
Délai: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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Total sleep time was recorded by participants in study diaries.
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- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4
Délai: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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Initial period of undisturbed sleep was the time elapsed from first falling asleep until either first void or morning arising.
Data were captured in patient diaries.
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- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4
Délai: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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The ICIQ-N is a self-administered questionnaire designed to assess the frequency and bother of daytime and nighttime urination.
Subjects were asked to rate the degree of bother of daytime urination and nighttime urination on a scale ranging from 0 (not at all) to 10 (a great deal).
Higher numbers indicate lower quality of life.
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- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4
Délai: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
|
The NQoL questionnaire is a self-administered 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 twelve core questions are scored on a 0 to 4 scale with higher numbers indicating a better quality of life.
Domain summary scores were calculated by transforming the raw score into a 0-100 scale with higher numbers indicating a better quality of life.
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- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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Part I: Change From Baseline in Quality of Sleep as Assessed by the Global Score of the Pittsburgh Sleep Quality Index (PSQI) at Week 4
Délai: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
|
The PSQI is a self-administered 19-item questionnaire designed to assess sleep quality and disturbances.
The global score ranges from 0 (better sleep quality) to 21 (worse sleep quality).
Higher numbers indicate lower quality of life.
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- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
|
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Part I: Change From Baseline in the Mental Health Summary and the Physical Health Summary of the Short Form-12 Version 2 (SF-12v2) at Week 4
Délai: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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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.
Data were analyzed using norm-based scoring and summarized along 2 dimensions: Physical Health Summary and Mental Health Summary.
Each summary has a range from 0 (poor health) to 100 (highest level of health).
Higher numbers indicate better quality of life.
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- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
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Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I
Délai: Day 1 up to Week 4 (end of Part I)
|
A treatment-emergent adverse event (AE) was any AE occurring during the treatment period or a pretreatment AE that worsened in intensity during the treatment period.
The treatment period was the period during which a subject received investigational medicinal product.
If a subject discontinued the investigational medicinal product, the date of last dose was the last day of the treatment period.
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Day 1 up to Week 4 (end of Part I)
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Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II
Délai: Week 5 up to Day 169
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A treatment-emergent adverse event (AE) was any AE occurring during the treatment period or a pretreatment AE that worsened in intensity during the treatment period.
The treatment period was the period during which a subject received investigational medicinal product.
If a subject discontinued the investigational medicinal product, the date of last dose was the last day of the treatment period.
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Week 5 up to Day 169
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Juul KV, Klein BM, Norgaard JP. Long-term durability of the response to desmopressin in female and male nocturia patients. Neurourol Urodyn. 2013 Apr;32(4):363-70. doi: 10.1002/nau.22306. Epub 2012 Sep 12.
- Weiss JP, Zinner NR, Klein BM, Norgaard JP. Desmopressin orally disintegrating tablet effectively reduces nocturia: results of a randomized, double-blind, placebo-controlled trial. Neurourol Urodyn. 2012 Apr;31(4):441-7. doi: 10.1002/nau.22243. Epub 2012 Mar 22.
- Juul KV, Malmberg A, van der Meulen E, Walle JV, Norgaard JP. Low-dose desmopressin combined with serum sodium monitoring can prevent clinically significant hyponatraemia in patients treated for nocturia. BJU Int. 2017 May;119(5):776-784. doi: 10.1111/bju.13718. Epub 2016 Dec 10.
- Bliwise DL, Holm-Larsen T, Goble S. Increases in duration of first uninterrupted sleep period are associated with improvements in PSQI-measured sleep quality. Sleep Med. 2014 Oct;15(10):1276-8. doi: 10.1016/j.sleep.2014.05.013. Epub 2014 Jun 13.
- 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.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 mai 2007
Achèvement primaire (Réel)
1 février 2008
Achèvement de l'étude (Réel)
1 février 2008
Dates d'inscription aux études
Première soumission
22 mai 2007
Première soumission répondant aux critères de contrôle qualité
22 mai 2007
Première publication (Estimation)
23 mai 2007
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
1 novembre 2015
Dernière mise à jour soumise répondant aux critères de contrôle qualité
29 septembre 2015
Dernière vérification
1 septembre 2015
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- FE992026 CS29
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .