Efficacy and Safety of Desmopressin Melt for the Treatment of Nocturia

Nocturia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00477490
• Other study ID #: FE992026 CS29
• Status: Completed
• Phase: Phase 3
• First received: May 22, 2007
• Last updated: September 29, 2015
• Start date: May 2007
• Est. completion date: February 2008

Study information

• Verified date: September 2015
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 799
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Nocturia

Intervention

Drug:
• desmopressin acetate
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
• Placebo
Oral placebo placed under the participant's tongue, without water, once daily approximately 1 hour before bedtime.

Locations

Country	Name	City	State
Canada	The Male/Female Health and Reserach	Barrie	Ontario
Canada	Brantford Urology Research	Brantford	Ontario
Canada	Investigational site - Professional Corporation	Fredericton	New Brunswick
Canada	Guelph Urology Associates	Guelph	Ontario
Canada	Southern Interior Medical Center	Kelowna	British Columbia
Canada	Investigational site	North Bay	Ontario
Canada	The Fe/Male Health Centres	Oakville	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Can-Med Clinical Research Inc.	Victoria	British Columbia
Canada	Investigational site - Clinical Research	Victoria	British Columbia
United States	Upstate Urology	Albany	New York
United States	Urology Group of New Mexico, PC	Albuquerque	New Mexico
United States	Advanced Urology Medical Center	Anaheim	California
United States	South Florida Medical Research	Aventura	Florida
United States	Urologic Consultants of SE PA	Bala Cynwyd	Pennsylvania
United States	Impact Clinical Trials	Beverly Hills	California
United States	Radiant Research	Birmingham	Alabama
United States	Investigational site - Adult & Pediatric Urology	Carmel	New York
United States	Radiant Research	Cincinnati	Ohio
United States	Women's Medical Research Group, LLC	Clearwater	Florida
United States	Southeastern Medical Research Institute	Columbus	Georgia
United States	Northeast Urology Research	Concord	North Carolina
United States	Advanced Research Associates	Corpus Christi	Texas
United States	Health Central Women's Care	Dallas	Texas
United States	Downtown Women's Health Care	Denver	Colorado
United States	Genitourinary Surgical Consultants	Denver	Colorado
United States	Urology Associates PC	Denver	Colorado
United States	Investigational site - PC	Dunwoody	Georgia
United States	AccuMed Research Associates	Garden City	New York
United States	PharmQuest	Greensboro	North Carolina
United States	University Medical Group	Greenville	South Carolina
United States	Radiant Research, Greer	Greer	South Carolina
United States	Accelovance	Houston	Texas
United States	Regional Medical Center and Diagnostic	Humble	Texas
United States	Holston Medical Group	Kingsport	Tennessee
United States	Investigational site	Las Vegas	Nevada
United States	AdvanceMed Research	Lawrenceville	New Jersey
United States	Lawrenceville Urology	Lawrenceville	New Jersey
United States	Women's Clinic of Lincoln, P.C	Lincoln	Nebraska
United States	Arkansas Primary Care Clinic	Little Rock	Arkansas
United States	Atlantic Urology Medical Group	Long Beach	California
United States	Benchmark Research	Metairie	Louisiana
United States	Medsearch Professional Group	Miami	Florida
United States	Connecticut Clinical Research Center, LLC	Middlebury	Connecticut
United States	Radiant Research - Akron	Mogadore	Ohio
United States	Morristown Urology	Morristown	New Jersey
United States	Palmetto Medical Research	Mt. Pleasant	South Carolina
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University Urology Associates	New York	New York
United States	California Professional Research	Newport Beach	California
United States	Radiant Research, Kansas City	Overland park	Kansas
United States	Accelovance	Peoria	Illinois
United States	Philadelphia Clinical Research, LLC	Philadelphia	Pennsylvania
United States	Radiant Research	Philadelphia	Pennsylvania
United States	Sunrise Medical Research	Plantation	Florida
United States	Advanced Clinical Concepts	Reading	Pennsylvania
United States	Virginia Urology Center	Richmond	Virginia
United States	Radiant Research San Antonio	San Antonio	Texas
United States	Urology San Antonio Research, PA	San Antonio	Texas
United States	San Diego Uro-Research	San Diego	California
United States	Radiant Research	Santa Rosa	California
United States	Radiant Research	Scottsdale	Arizona
United States	Investigational site - Medical Professional	Seattle	Washington
United States	Seattle Urology Research Center	Seattle	Washington
United States	Women's Clinical Research Center	Seattle	Washington
United States	Pierremont Women's Clinic	Shreveport	Louisiana
United States	Regional Urology, LLC	Shreveport	Louisiana
United States	FutureCare Studies, Inc.	Springfield	Massachusetts
United States	Radiant Research Inc.	St. Louis	Missouri
United States	Radiant Research	Stuart	Florida
United States	Ferring Pharmaceutical Inc	Suffern	New York
United States	Southeastern Research Group, Inc.	Tallahassee	Florida
United States	Tampa Bay Urology	Tampa	Florida
United States	West Coast Clinical Research	Tarzana	California
United States	Western Clinical Research	Torrance	California
United States	Urology of Virginia PC	Virginia Beach	Virginia
United States	Radiant Research	West Palm Beach	Florida
United States	New Hanover Medical Research	Wilmington	North Carolina
United States	Piedmont Medical Research Associates	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

Juul KV, Klein BM, Nørgaard 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. Review. — View Citation

Weiss JP, Zinner NR, Klein BM, Nørgaard 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4	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)	No
Primary	Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4	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)	No
Secondary	Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169	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.	- Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169	No
Secondary	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	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.	- Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169	No
Secondary	Part I: Change From Baseline in Total Reported Sleep Time at Week 4	Total sleep time was recorded by participants in study diaries.	- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)	No
Secondary	Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4	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.	- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)	No
Secondary	Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4	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.	- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)	No
Secondary	Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4	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.	- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)	No
Secondary	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	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.	- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)	No
Secondary	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	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.	- Week 3 to Day 1 (Baseline), Week 4 (end of Part I)	No
Secondary	Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study 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.	Day 1 up to Week 4 (end of Part I)	No
Secondary	Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II	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.	Week 5 up to Day 169	No