A Phase IIb Randomized, Placebo- and Active Comparator (Tolterodine)-Controlled, 2-Part Clinical Study of the Efficacy and Safety of MK-4618 in Patients with Overactive Bladder - PhIIb Dose Ranging Study

Active, not recruiting

• Conditions: Overactive Bladder; MedDRA version: 14.1Level: LLTClassification code 10059617Term: Overactive bladderSystem Organ Class: 100000004857; Therapeutic area: Health Care [N] - Health Care Quality, Access, and Evaluation [N05]

• Registration Number: EUCTR2010-022121-15-PL
• Lead Sponsor: Merck Sharpe & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05-30
• Last Update Posted: 16 December 2013

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 1405

Inclusion Criteria

Base protocol:
1. Patient is male or female between 18 and 75 years of age inclusive on day of signing informed consent. 2. A female patient who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control within the projected duration of the study. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with permicide, contraceptive sponge, condom, vasectomy. A female patient who is not of reproductive potential is eligible without requiring the use of contraception. A female patient who is not of reproductive potential is defined as: one who has either 1) reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum FSH levels in the postmenopausal range as determined by the laboratory, or 12 months of spontaneous amenorrhea), 2) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy, 3) bilateral tubal ligation, or 4) hysterectomy. 3. Patient has a clinical history of OAB (may be verbal per patient) for at least 3 months prior to Visit 1. OAB is defined as urgency, with or without urge incontinence, usually associated with frequency and nocturia. Urodynamic evaluation is not required. 3. Patient is able to read, understand and complete questionnaires and voiding diaries as well as collect, measure and record voided volume by herself/himself using a graduated beaker, which will be provided by the SPONSOR. 4. Patient meets either the OAB wet or OAB dry criteria described below based on the screening diary returned at Visit 2 and the placebo run-in diary returned at Visit 3: • OAB wet criteria: An average of = 8 micturitions/day and average number of urge incontinence episodes is = 1 per diary day AND the total number of urge incontinence episodes exceeds the total number of stress incontinence episodes from the screening diary. OR • OAB dry criteria: An average of = 8 micturitions/day and the average number of strong urge episodes is = 3 per diary day from the screening diary.
Extension:
Patient must meet ALL of the following criteria before entering the 52-week extension.
Visit 1 Inclusion Criteria
1. Patient completed either Part 1 or Part 2 of Protocol 008.
2. Patient is able to understand study procedures and agrees to participate in the extension study by giving written informed consent.
3. A female patient who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control within the projected duration of the study. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, vasectomy. A female patient who is not of reproductive potential is eligible without requiring the use of contraception. A female patient who is not of reproductive potential is defined as: one who has either 1) reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum FSH levels in the postmenopausal range as determined by the laboratory, or 12 months of spontaneous amenorrhea), 2) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy, 3) bilateral tubal ligation, or 4) hysterectomy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Base protocol:
1.Patient has evidence of diabetes insipidus, uncontrolled hyperglycemia (fasting blood glucose >150 mg/dL or 8.33 mmol/l and/or non fasting blood glucose >180 mg/dL or 10.0 mmol/l), or uncontrolled hypercalcemia (blood total calcium >11 mg/dL or 2.75 mmol/l). 2.Patient has a resting systolic blood pressure > 160 mmHg or resting diastolic blood pressure >90 mmHg or resting heart rate (by pulse) > 100 beats per minute at Visit 1. 3. Patient is pregnant or breast-feeding, or expecting to conceive within the projected duration of the study. 4.Patient has a history of cerebral vascular accident, transient ischemic attack, unstable angina, or myocardial infarction within the previous 6 months. 5.Patient has lower urinary tract pathology that could, in the opinion of the investigator, be responsible for urgency, frequency, or incontinence; including but not limited to urolithiasis, interstitial cystitis, urothelial tumor, prostatitis, and clinically relevant benign prostatic hypertrophy or bladder outlet obstruction as judged by the investigator. 6.Patient has a history of injury, surgery, or neurodegenerative diseases (e.g., multiple sclerosis) that could affect the lower urinary tract or its nerve supply. 7.Patient has a history of continual urine leakage or patient is unaware of urine leakage. 8.Patient has a history of surgery to correct stress urinary incontinence or pelvic organ prolapse within 6 months. 9.Patient has a known history of elevated postvoid residual defined per the investigator's local standard of care. 10.Patient has undergone bladder training or electrostimulation within 2 weeks prior to Visit 1 or plans to initiate either during the study. 11.Patient has active or recurrent (>6 episodes per year) urinary tract infections by clinical history, clinical symptoms, or laboratory criteria (= 5 WBC or = 26 bacteria (moderate) per high-powered field in a spun specimen and/or a positive urine culture defined as = 104 colony forming units (CFU)/mL in 1 specimen. 12.Patient has hematuria, including microscopic hematuria (> 5 RBCs/hpf). 13.Patient has a requirement for an indwelling catheter or intermittent catheterization. 14.Patient has a history of fecal incontinence. 15.Patient is not willing to discontinue use of the following therapies at least 2 weeks prior to completing the screening voiding diary and remain off these therapies for the duration of the study: •Anticholinergics including but not limited to oxybutynin, tolterodine, trospium, darifenacin, solifenacin, fesoterodine, hyoscyamine, and propantheline. •Smooth muscle relaxants including but not limited to flavoxate, dicyclomine, propiverine. •Beta 2 adrenergic agonists used for the treatment of stress urinary incontinence including but not limited to clenbuterol. •Synthetic antidiuretic hormones, including but not limited to desmopressin. •Phosphodiesterase type 5 (PDE 5) inhibitors, including but not limited to tadalafil, sidenafil and vardenafil. •Beta 3 adrenergic agonists, including but not limited to mirabegron.
16. Patient is currently taking or has taken within the past 6 months 5-alpha reductase inhibitors or herbal remedies for the treatment of benign prostatic hypertrophy.
Extension:
Patient MUST be excluded if he/she meets ANY of the following exclusion criteria.
Visit 1 Exclusion Criteria
1. Patient had any serious, drug-related, or unresolved clinical or laboratory adverse experiences during participation in Protocol 008 that in th

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified