Interventional Clinical Trial in Patients in Overactive Bladder With Nocturia in Women

A Multi-centre, Double-blind, Randomised Trial Investigating the Efficacy and Safety of a Combination Therapy, Desmopressin and Tolterodine, for Treatment of Overactive Bladder With Nocturia in Women

The purpose of the trial is to investigate the efficacy of combining tolterodine and desmopressin compared with tolterodine monotherapy in the treatment of women with overactive bladder with nocturia in terms of reduction of nocturnal voids during 3 months of treatment

Inclusion Criteria:

• Written informed consent prior to performance of any trial-related activity
• Female sex, at least 18 years of age (at the time of written consent)
• Nocturia and overactive bladder symptoms present for ≥6 months prior to trial entry (patient-reported)
• At least 2 nocturnal voids each night as documented in 2 diary periods during the screening. A mean of at least 8 daytime voids per day over 3 days with a minimum of at least 6 daytime voids each day as documented in 2 diary periods during the screening. At least 1 urgency episode each 24 hours as documented in 2 diary periods during the screening. Each diary period consists of 3 consecutive days, with at least 14 days between each period.

Exclusion Criteria:

• Evidence of severe voiding dysfunction defined as:

More than 10 nocturnal voids per 24 hours as documented on any of the days in both diary periods during screening.

More than 20 daytime voids per 24 hours as documented on any of the days in both diary periods during screening.

• Genito-urinary tract pathology that can in the investigator's opinion be responsible for urgency or urinary incontinence e.g., symptomatic or recurrent urinary tract infections, interstitial cystitis, bladder related pain, or stone in the bladder and urethra causing symptoms
• Current or a history within 5 years of lower urologic malignancies (e.g., bladder cancer), lower urinary tract surgery, previous pelvic irradiation, or severe neurological disease affecting bladder function or muscle strength (e.g., multiple sclerosis, Parkinson's disease, spinal cord injury, spina bifida)
• Symptoms of severe stress urinary incontinence in the opinion of the investigator
• Urinary retention or a post void residual volume in excess of 150 mL as confirmed by bladder ultrasound performed after suspicion of urinary retention
• Habitual or psychogenic polydipsia (fluid intake resulting in a urine production exceeding 40 mL/kg/24 hours) or a mean volume voided per void of 350 mL or more during one or more 24-hour periods as assessed by the screening diaries
• Central or nephrogenic diabetes insipidus
• Syndrome of inappropriate antidiuretic hormone (SIADH)
• Gastric retention
• Myasthenia gravis
• Uncontrolled narrow-angle glaucoma
• Suspicion or evidence of cardiac failure
• Uncontrolled and clinically relevant (in the judgement of the investigator) hypertension or diabetes mellitus
• History and/or current treatment of obstructive sleep apnoea
• Hyponatraemia:Serum sodium level must not be below 135 mmol/L
• Evidence of potential renal impairment:Serum creatinine must be within normal laboratory reference intervals AND estimated glomerular filtration rate must be more than or equal to 50 mL/min
• Hepatic and/or biliary diseases: Aspartate aminotransferase and/or alanine aminotransferase levels must not be more than twice the upper limit of normal range. Total bilirubin level must not be more than 1.5 mg/dL
• Pregnancy, breastfeeding, or a plan to become pregnant during the period of the trial. Women of reproductive age must have documentation of a reliable method of contraception. All pre- and perimenopausal women have to perform pregnancy tests. Amenorrhea of more than 12 months duration based on the reported date of the last menstrual period is sufficient documentation of post-menopausal status and does not require a pregnancy test
• Known alcohol or substance abuse; work or lifestyle that may interfere with regular night-time sleep e.g., shift workers; or any other medical condition, laboratory abnormality, psychiatric condition, mental incapacity, illiteracy or language barrier which, in the judgement of the investigator, would impair participation in the trial
• Known or suspected hypersensitivity to any active ingredient or excipients in the investigational medicinal products used in the trial
• Previous participation in any desmopressin trial within the last 5 years
• Use of any prohibited therapy, as defined in the protocol