Efficacy and Safety of Desmopressin Melt for the Treatment of Nocturia
Condition: Nocturia
MeSH terms: Nocturia
Intervention: desmopressin acetate; Placebo
Intervention description: 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; Oral placebo placed under the participant's tongue, without water, once daily approximately 1 hour before bedtime.
Intervention MeSH terms: Deamino Arginine Vasopressin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 799.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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