Efficacy and Safety of Desmopressin Melt for the Treatment of Nocturia

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