A phase 2, 26 week, multicenter, randomized double blind, placebo controlled, crossover study evaluating the efficacy and safety of tolterodine, pregabalin and a tolterodine-pregabalin combination for idiopathic overactive bladder. - N/A

• Conditions: Overactive bladder syndrome; MedDRA version: 8.0Level: LLTClassification code 10059617

• Registration Number: EUCTR2005-004249-33-CZ
• Lead Sponsor: Pfizer Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-12-01
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 170

Inclusion Criteria

1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the trial.
2. Women =18 years old with symptoms of urinary frequency (=8 micturitions on average per 24 hours) and urgency of a minimum of 4 episodes per week (defined as a sudden and compelling desire to pass urine which is difficult to defer) as confirmed by the bladder diary completed prior to Visit 2. As the diary will not be recorded over a whole week, at least 3 episodes over a complete 4-day diary period will define urgency. Subjects may or may not have incontinence.
3. Female subjects must be non-pregnant and non-lactating, and be either postmenopausal (either over the age of 60 years, or if below this age > 1 year without menses), surgically sterilized, or using an appropriate method of contraception (including barrier or hormonal methods). Subjects of child bearing potential must have confirmed negative urine pregnancy tests taken at Visit 2 (prior to randomization).
4. Mean volume voided <300 ml as verified by the bladder diary completed prior to visit 2.
5. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, the self-completion of study questionnaires and urinary diaries, and other trial procedures.
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) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects presenting with any of the following will not be included in the trial:
1. Subjects with symptoms of overactive bladder for less than 6 months prior to randomization.
2. Significant stress incontinence as determined by the investigator e.g. stress predominant mixed incontinence, positive cough provocation test.
3. Subjects with a documented and untreated urinary tract infection (UTI) at Visit 1. Subjects with a positive (1+ or greater) leukocyte or nitrite result in their urine dipstick test will be excluded unless a UTI can be ruled out via urine culture.
4. Subjects with a relevant neurological disease with which their urinary symptoms may be associated (e.g. multiple sclerosis, Parkinson’s disease, spinal cord lesion, familial neuropathy, and previous cerebrovascular accident).
5. Subjects with infrequent bowel movements.
6. Subjects with cystocele or other clinically significant pelvic prolapse beyond the hymen.
7. Subjects who have undergone urogenital surgery such as hysterectomy less than 6 months prior to screening, and subjects who have undergone bladder biopsy or cystoscopy less than 15 days prior to screening.
8. Subjects with diagnosed or suspected chronic persistent local lower urinary tract pathology (e.g. bladder stone, interstitial cystitis, transitional cell carcinoma, recurrent gross hematuria, recurrent urinary tract infection (UTI) – defined as >1 UTI over the past year) or subjects who have a history of pelvic radiotherapy.
9. Subjects with greater than 1+ of hematuria on dipstick test, unless fully investigated prior to randomization to rule out significant urological disease.
10. Subjects with a total volume voided of > 3000 ml on average per 24 hours, as confirmed by the bladder diary completed prior to Visit 2.
11. Subjects with a post-void residual (PVR) of > 200ml.
12. Subjects who have received any electro-stimulation therapy or bladder retraining within three months of Visit 1, or who are expected to start such therapy during the study period.
13. Subjects with an indwelling catheter or who practice intermittent self-catheterization, or are incapable of independent toileting.
14. Subjects with any condition that would contraindicate the use of tolterodine or pregabalin.
15. Subjects treated within the last 28 days preceding visit 2 (randomization), or expected to start therapy during the study treatment period with:
- Any drug with anticholinergic activity including benzatropine, biperidin, bornaprin, cyclopentolate, orphenadrine, procyclidine, and trihexyphenidyl.
- Anti-spasmodic drugs including hyoscine, hyoscyamine, mepenzolate, glycopyrronium, flavoxate, dicycloverine, atropine and propantheline.
- Any drug for overactive bladder or incontinence, with the exception of any estrogen or hormone replacement therapy treatment started more than 3 months prior to Visit 2.
- Intermittent or off-label use or unstable dose of diuretics.
16. Subjects receiving any treatment with vigabatrin, hydroxychloroquine, deferoxamine, thiorizidine or any compound known to adversely affect the retina and visual field.
17. Subjects with known hypersensitivity or poor toleration to anticholinergics or a2d ligands (including excipients).
18. Subjects receiving concomitant treatment with potent CYP3A4 inhibitors, such as macrolide antibiotics (erythromycin clarithromycin, azithromycin) and anti-proteases or antifungal agents (ketoconazole, itraconazole, miconazole; topical antifungal agents are permitted) or subjects e

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: · Assess the efficacy and safety of a standard dose antimuscarinic (tolterodine SR 4 mg once daily)/a2d ligand (pregabalin 150 mg twice daily) combination for the treatment of idiopathic OAB syndrome compared with standard therapy (tolterodine SR 4 mg once daily).<br>· Assess the efficacy and safety of an a2d ligand (pregabalin 150 mg twice daily) for the treatment of idiopathic OAB syndrome compared with standard therapy (tolterodine SR 4 mg once daily) and placebo.<br>· Determine potential for a synergistic effect with the combination.<br>· Compare efficacy and safety of a low dose antimuscarinic (tolterodine SR 2 mg once daily)/a2d ligand (pregabalin 75 mg twice daily) combination for the treatment of idiopathic OAB syndrome with standard therapy (tolterodine SR 4 mg once daily).;Secondary Objective: ;Primary end point(s): Change in mean voided volume per micturition (from baseline) after 4 weeks of treatment.