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Efficacy and Safety of Desmopressin Melt for the Treatment of Nocturia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00477490
First received: May 22, 2007
Last updated: September 29, 2015
Last verified: September 2015
  Purpose
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.

Condition Intervention Phase
Nocturia
Drug: desmopressin acetate
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Ferring Pharmaceuticals:

Primary Outcome Measures:
  • Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4 [ Time Frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I) ] [ Designated as safety issue: No ]

    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.


  • Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4 [ Time Frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 [ Time Frame: - Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: - Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169 ] [ Designated as safety issue: No ]
    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.

  • Part I: Change From Baseline in Total Reported Sleep Time at Week 4 [ Time Frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I) ] [ Designated as safety issue: No ]
    Total sleep time was recorded by participants in study diaries.

  • Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4 [ Time Frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I) ] [ Designated as safety issue: No ]
    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.

  • Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 [ Time Frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I) ] [ Designated as safety issue: No ]
    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.

  • Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 [ Time Frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I) ] [ Designated as safety issue: No ]
    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.

  • Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I [ Time Frame: Day 1 up to Week 4 (end of Part I) ] [ Designated as safety issue: No ]
    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.

  • Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II [ Time Frame: Week 5 up to Day 169 ] [ Designated as safety issue: No ]
    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.


Enrollment: 799
Study Start Date: May 2007
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 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).
Drug: Placebo
Oral placebo placed under the participant's tongue, without water, once daily approximately 1 hour before bedtime.
Experimental: 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).
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
Other Names:
  • Minirin® Melt
  • Nocturin®
  • FE992026
Experimental: 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).
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
Other Names:
  • Minirin® Melt
  • Nocturin®
  • FE992026
Experimental: 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).
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
Other Names:
  • Minirin® Melt
  • Nocturin®
  • FE992026
Experimental: 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).
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
Other Names:
  • Minirin® Melt
  • Nocturin®
  • FE992026

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00477490

  Show 80 Study Locations
Sponsors and Collaborators
Ferring Pharmaceuticals
Investigators
Study Director: Clinical Development Support Ferring Pharmaceuticals
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00477490     History of Changes
Other Study ID Numbers: FE992026 CS29 
Study First Received: May 22, 2007
Results First Received: June 16, 2015
Last Updated: September 29, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
Nocturia
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Deamino Arginine Vasopressin
Hemostatics
Coagulants
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 08, 2016