Clinical trial NCT00477490: Efficacy and Safety of Desmopressin Melt for the Treatment of Nocturia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nocturia
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-05-23
Enrollment: 799
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria

1. Written informed consent prior to the performance of any study-related activity.
2. 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:

1. 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
2. Surgical treatment for bladder outlet obstruction/benign prostatic hyperplasia performed within the past 6 months

   Females:
3. Pregnancy. Females of reproductive age must have documentation of a reliable method of contraception.
4. Use of pessary for pelvic prolapse.
5. Unexplained pelvic mass.

   Males and Females:
6. 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.
7. Current or past urologic malignancy (e.g., bladder cancer, prostate cancer).
8. Clinical evidence of current genitourinary tract pathology that could interfere with voiding.
9. History of neurogenic detrusor activity (previously known as detrusor hyperreflexia).
10. Suspicion or evidence of cardiac failure.
11. Uncontrolled hypertension.
12. Uncontrolled diabetes mellitus.
13. Renal insufficiency. Serum creatinine must be within normal limits and estimated glomerular filtration rate (eGFR) \>=60 mL/min.
14. 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.
15. Hyponatremia. Serum sodium level must be within normal limits
16. Syndrome of Inappropriate antidiuretic hormone secretion (SIADH).
17. Diabetes insipidus (urine output \> 40 ml/kg over 24 hours) as determined by the 3-day voiding diary.
18. Psychogenic or habitual polydipsia
19. Obstructive sleep apnea

    Other
20. Known alcohol or substance abuse
21. Work or lifestyle potentially interfering with regular nighttime sleep (e.g., shift workers)
22. Previous desmopressin treatment for nocturia.
23. 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.
24. 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.
25. 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

Primary outcomes:
measure: Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4
timeFrame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
measure: Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4
timeFrame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
Secondary outcomes:
measure: Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169
timeFrame: - Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169
measure: 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
timeFrame: - Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169
measure: Part I: Change From Baseline in Total Reported Sleep Time at Week 4
timeFrame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
measure: Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4
timeFrame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
measure: Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4
timeFrame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
measure: Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4
timeFrame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
measure: 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
timeFrame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
measure: 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
timeFrame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
measure: Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I
timeFrame: Day 1 up to Week 4 (end of Part I)
measure: Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II
timeFrame: Week 5 up to Day 169
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Radiant Research
state: Alabama
city: Scottsdale
country: United States
facility: Radiant Research
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Primary Care Clinic
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Urology Medical Center
state: California
city: Beverly Hills
country: United States
facility: Impact Clinical Trials
state: California
city: Long Beach
country: United States
facility: Atlantic Urology Medical Group
state: California
city: Newport Beach
country: United States
facility: California Professional Research
state: California
city: San Diego
country: United States
facility: San Diego Uro-Research
state: California
city: Santa Rosa
country: United States
facility: Radiant Research
state: California
city: Tarzana
country: United States
facility: West Coast Clinical Research
state: California
city: Torrance
country: United States
facility: Western Clinical Research
state: California
city: Denver
country: United States
facility: Urology Associates PC
state: Colorado
city: Denver
country: United States
facility: Downtown Women's Health Care
state: Colorado
city: Denver
country: United States
facility: Genitourinary Surgical Consultants
state: Colorado
city: Middlebury
country: United States
facility: Connecticut Clinical Research Center, LLC
state: Connecticut
city: Aventura
country: United States
facility: South Florida Medical Research
state: Florida
city: Clearwater
country: United States
facility: Women's Medical Research Group, LLC
state: Florida
city: Miami
country: United States
facility: Medsearch Professional Group
state: Florida
city: Plantation
country: United States
facility: Sunrise Medical Research
state: Florida
city: Stuart
country: United States
facility: Radiant Research
state: Florida
city: Tallahassee
country: United States
facility: Southeastern Research Group, Inc.
state: Florida
city: Tampa
country: United States
facility: Tampa Bay Urology
state: Florida
city: West Palm Beach
country: United States
facility: Radiant Research
state: Florida
city: Columbus
country: United States
facility: Southeastern Medical Research Institute
state: Georgia
city: Dunwoody
country: United States
facility: Investigational site - PC
state: Georgia
city: Peoria
country: United States
facility: Accelovance
state: Illinois
city: Overland park
country: United States
facility: Radiant Research, Kansas City
state: Kansas
city: Metairie
country: United States
facility: Benchmark Research
state: Louisiana
city: Shreveport
country: United States
facility: Regional Urology, LLC
state: Louisiana
city: Shreveport
country: United States
facility: Pierremont Women's Clinic
state: Louisiana
city: Springfield
country: United States
facility: FutureCare Studies, Inc.
state: Massachusetts
city: St. Louis
country: United States
facility: Radiant Research Inc.
state: Missouri
city: Lincoln
country: United States
facility: Women's Clinic of Lincoln, P.C
state: Nebraska
city: Las Vegas
country: United States
facility: Investigational site
state: Nevada
city: Lawrenceville
country: United States
facility: AdvanceMed Research
state: New Jersey
city: Lawrenceville
country: United States
facility: Lawrenceville Urology
state: New Jersey
city: Morristown
country: United States
facility: Morristown Urology
state: New Jersey
city: Albuquerque
country: United States
facility: Urology Group of New Mexico, PC
state: New Mexico
city: Albany
country: United States
facility: Upstate Urology
state: New York
city: Carmel
country: United States
facility: Investigational site - Adult & Pediatric Urology
state: New York
city: Garden City
country: United States
facility: AccuMed Research Associates
state: New York
city: New York
country: United States
facility: University Urology Associates
state: New York
city: Suffern
country: United States
facility: Ferring Pharmaceutical Inc
state: New York
city: Concord
country: United States
facility: Northeast Urology Research
state: North Carolina
city: Greensboro
country: United States
facility: PharmQuest
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Medical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Medical Research Associates
state: North Carolina
city: Cincinnati
country: United States
facility: Radiant Research
state: Ohio
city: Mogadore
country: United States
facility: Radiant Research - Akron
state: Ohio
city: Bala Cynwyd
country: United States
facility: Urologic Consultants of SE PA
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia Clinical Research, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Radiant Research
state: Pennsylvania
city: Reading
country: United States
facility: Advanced Clinical Concepts
state: Pennsylvania
city: Greenville
country: United States
facility: University Medical Group
state: South Carolina
city: Greer
country: United States
facility: Radiant Research, Greer
state: South Carolina
city: Mt. Pleasant
country: United States
facility: Palmetto Medical Research
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Corpus Christi
country: United States
facility: Advanced Research Associates
state: Texas
city: Dallas
country: United States
facility: Health Central Women's Care
state: Texas
city: Houston
country: United States
facility: Accelovance
state: Texas
city: Humble
country: United States
facility: Regional Medical Center and Diagnostic
state: Texas
city: San Antonio
country: United States
facility: Radiant Research San Antonio
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio Research, PA
state: Texas
city: Richmond
country: United States
facility: Virginia Urology Center
state: Virginia
city: Virginia Beach
country: United States
facility: Urology of Virginia PC
state: Virginia
city: Seattle
country: United States
facility: Women's Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: Investigational site - Medical Professional
state: Washington
city: Seattle
country: United States
facility: Seattle Urology Research Center
state: Washington
city: Kelowna
country: Canada
facility: Southern Interior Medical Center
state: British Columbia
city: Victoria
country: Canada
facility: Can-Med Clinical Research Inc.
state: British Columbia
city: Victoria
country: Canada
facility: Investigational site - Clinical Research
state: British Columbia
city: Fredericton
country: Canada
facility: Investigational site - Professional Corporation
state: New Brunswick
city: Barrie
country: Canada
facility: The Male/Female Health and Reserach
state: Ontario
city: Brantford
country: Canada
facility: Brantford Urology Research
state: Ontario
city: Guelph
country: Canada
facility: Guelph Urology Associates
state: Ontario
city: North Bay
country: Canada
facility: Investigational site
state: Ontario
city: Oakville
country: Canada
facility: The Fe/Male Health Centres
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Ferring Pharmaceuticals
name: Clinical Development Support
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.