| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Overactive bladder syndrome |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10059617 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
· Assess the efficacy and safety of a standard dose antimuscarinic (tolterodine SR 4 mg once daily)/α2δ ligand (pregabalin 150 mg twice daily) combination for the treatment of idiopathic OAB syndrome compared with standard therapy (tolterodine SR 4 mg once daily).
· Assess the efficacy and safety of an α2δ 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.
· Determine potential for a synergistic effect with the combination.
· Compare efficacy and safety of a low dose antimuscarinic (tolterodine SR 2 mg once daily)/α2δ ligand (pregabalin 75 mg twice daily) combination for the treatment of idiopathic OAB syndrome with standard therapy (tolterodine SR 4 mg once daily). |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal 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. |
|
| E.4 | Principal 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 α2δ 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 expected to start such treatment during the study.
19. Subjects with significant hepatic disease, defined as twice the upper limit of the reference ranges of serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP).
20. Subjects with a creatinine clearance ≤30 mL/min.
21. Subjects with intention to donate blood/blood products during the study or up to one month after completion of the study.
22. Subjects with a history of malignancy within the past 2 years with the exception of basal cell carcinoma.
23. Subjects with a history of alcohol or drug abuse in the past 2 years.
24. Subjects with recent receipt of investigational drug.
25. Subjects who in the opinion of the investigator, or that of the Pfizer clinician, are unable and/or unlikely to comprehend the nature, scope and possible consequences of the study and to follow the study procedures and instructions and complete all study related measurements.
26. Subjects with other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator or Pfizer clinician, would make the subject inappropriate for entry into this trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change in mean voided volume per micturition (from baseline) after 4 weeks of treatment. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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