Clinical Drug Investigation

, Volume 29, Issue 5, pp 305–316 | Cite as

Diary and Patient-Reported Outcomes in Patients with Severe Overactive Bladder Switching from Tolterodine Extended Release 4mg/day to Solifenacin Treatment

An Open-Label, Flexible-Dosing, Multicentre Study
  • Steven E. Swift
  • Paul Siami
  • Sergio Forero-Schwanhaeuser
Original Research Article

Abstract

Objective: We report outcomes from the VERSUS (VESIcare® Efficacy and Research Study US) study in a cohort with severe overactive bladder (OAB), defined as patients with a score ≥5 on the Patient Perception of Bladder Condition (PPBC) scale at baseline (on tolterodine extended release [ER] 4mg/day) who remained severe at post-washout (on no drug).

Methods: VERSUS was a 12-week, open-label, flexible-dosing study assessing the efficacy, tolerability and effects on health-related quality of life (HRQOL) of solifenacin in patients with OAB. The current study is a post hoc analysis of a severely affected subgroup, as self-defined using the PPBC scale. Patients had received tolterodine ER 4mg/day for ≥4 weeks but wished to switch therapy because of a lack of sufficient subjective improvement in urgency. They had to have continued to have three or more urgency episodes/24 hours at baseline (pre-washout, i.e. while taking tolterodine ER 4mg/day). After ≥14 days’ washout, patients received oral solifenacin 5mg/day, with the option of continuing/adjusting the dose to 5 or 10mg/day at weeks 4 and 8. Diary-documented improvements in urgency, urge incontinence, frequency, nocturia and nocturnal voids were compared with pre-washout (on tolterodine) and post-washout (on no drug) diary entries. The PPBC scale and Overactive Bladder Questionnaire (OAB-q) assessed patient-reported outcomes. Tolerability was evaluated based on the nature, frequency and severity of observed or reported adverse events (AEs).

Results: In this severe OAB cohort, the mean number of urgency episodes/24 hours decreased by 3.95 (95% CI −4.81, −3.08; p <0.0001) from pre-washout (7.38) to study end (3.26). All other diary variables were also significantly reduced (p <0.0001). Patients had a mean PPBC score of 5.3 at pre-washout and 3.6 at study end, representing an improvement of 1.7 (95% CI −2.0, −1.5; p <0.0001). Patients also reported significant improvements for all OAB-q scales and domains (p <0.0001). Treatment-emergent AEs were mostly mild/moderate, and resulted in few discontinuations (5/116, 4.3%).

Conclusion: In patients with severe OAB symptoms, solifenacin was effective and well tolerated. Solifenacin improved urgency, incontinence, micturition frequency, nocturia and nocturnal voids in patients continuing to experience urgency episodes on tolterodine ER 4mg/day. Patients experienced improvements in HRQOL and perceived bother from OAB.

Keywords

Tolterodine Solifenacin Trospium Chloride Urgency Episode Bladder Condition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This study was supported by Astellas Pharma US, Inc. and GlaxoSmithKline. Clinical study number: 905-UC-006; trial registry number: NCT00454740.

The authors would like to thank the entire clinical development team, led by Allam Fakhoury, PharmD, for their contributions to the success of this programme. Medical writing and editorial support was provided by Sue Cooper at Envision Pharma.

Dr Swift currently receives or has previously received research grants from Duramed, Pfizer and Astellas, is on the speakers bureau for Pfizer and Astellas, and is on the Advisory Board for Merck, Pfizer and Astellas. Dr Siami is currently or was previously a consultant and speaker for Bard, Astellas, GlaxoSmithKline, Pfizer and Boehringer-Ingelheim, an investigator for Pharmacia, Bayer and GlaxoSmithKline, and on the Advisory Board for Bayer and GlaxoSmithKline. Dr Forero-Schwanhaeuser is an employee of GlaxoSmithKline.

References

  1. 1.
    Abrams P, Artibani W, Cardozo L, et al. Reviewing the ICS 2002 Terminology Report: the ongoing debate [letter]. Neurourol Urodyn 2006; 25(3): 293CrossRefGoogle Scholar
  2. 2.
    Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol 2003 May; 20(6): 327–36PubMedGoogle Scholar
  3. 3.
    Milsom I, Abrams P, Cardozo L, et al. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int 2001 Jun; 87(9): 760–6PubMedCrossRefGoogle Scholar
  4. 4.
    Girman CJ, Jacobsen SJ, Tsukamoto T, et al. Health-related quality of life associated with lower urinary tract symptoms in four countries. Urology 1998 Mar; 51(3): 428–36PubMedCrossRefGoogle Scholar
  5. 5.
    van Kerrebroeck P, Abrams P, Lange R, et al. Duloxetine versus placebo in the treatment of European and Canadian women with stress urinary incontinence. BJOG 2004 Mar; 111(3): 249–57PubMedCrossRefGoogle Scholar
  6. 6.
    Sussman D, Garely A. Treatment of overactive bladder with once-daily extended-release tolterodine or oxybutynin: the Antimuscarinic Clinical Effectiveness Trial (ACET). Curr Med Res Opin 2002; 18(4): 177–84PubMedCrossRefGoogle Scholar
  7. 7.
    Landis JR, Kaplan S, Swift S, et al. Efficacy of antimuscarinic therapy for overactive bladder with varying degrees of incontinence severity. J Urol 2004 Feb; 171 (2 Pt 1): 752–6PubMedCrossRefGoogle Scholar
  8. 8.
    Preik M, Albrecht D, O’Connell M, et al. Effect of controlled-release delivery on the pharmacokinetics of oxybutynin at different dosages: severity-dependent treatment of the overactive bladder. BJU Int 2004 Oct; 94(6): 821–7PubMedCrossRefGoogle Scholar
  9. 9.
    Coyne KS, Matza LS, Kopp Z, et al. The validation of the Patient Perception of Bladder Condition (PPBC): a single-item global measure for patients with overactive bladder. Eur Urol 2006 Jun; 49(6): 1079–86PubMedCrossRefGoogle Scholar
  10. 10.
    Burgio KL, Matthews KA, Engel BT. Prevalence, incidence and correlates of urinary incontinence in healthy, middle-aged women. J Urol 1991 Nov; 146(5): 1255–9PubMedGoogle Scholar
  11. 11.
    Haab F, Castro-Diaz D. Persistence with antimuscarinic therapy in patients with overactive bladder. Int J Clin Pract 2005 Aug; 59(8): 931–7PubMedCrossRefGoogle Scholar
  12. 12.
    Cardozo L, Lisec M, Millard R, et al. Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder. J Urol 2004 Nov; 172 (5 Pt 1): 1919–24PubMedCrossRefGoogle Scholar
  13. 13.
    Chapple CR, Arano P, Bosch JL, et al. Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo-and tolterodine-controlled phase 2 dose-finding study. BJU Int 2004 Jan; 93(1): 71–7PubMedCrossRefGoogle Scholar
  14. 14.
    Kelleher CJ, Cardozo L, Chapple CR, et al. Improved quality of life in patients with overactive blader symptoms treated with solifenacin. BJU Int 2005 Jan; 95(1): 81–5PubMedCrossRefGoogle Scholar
  15. 15.
    Mattiasson A, Djurhuus JC, Fonda D, et al. Standardization of outcome studies in patients with lower urinary tract dysfunction: a report on general principles from the Standardization Committee of the International Continence Society. Neurourol Urodyn 1998; 17: 249–53PubMedCrossRefGoogle Scholar
  16. 16.
    Chancellor MB, Zinner N, Whitmore K, et al. Efficacy of solifenacin in patients previously treated with tolterodine extended release 4mg: results of a 12-week, multicenter, open-label, flexible-dose study. Clin Ther 2008 Oct; 30(10): 1766–81PubMedCrossRefGoogle Scholar
  17. 17.
    Coyne KS, Matza LS, Thompson C, et al. The responsiveness of the OAB-q among OAB patient subgroups. Neurourol Urodyn 2007; 26(2): 196–203PubMedCrossRefGoogle Scholar
  18. 18.
    Coyne KS, Matza LS, Thompson CL, et al. Determining the importance of change in the overactive bladder questionnaire. J Urol 2006 Aug; 176(2): 627–32PubMedCrossRefGoogle Scholar
  19. 19.
    Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology 2003 Jan; 61(1): 37–49PubMedCrossRefGoogle Scholar
  20. 20.
    van Kerrebroeck P, Abrams P, Chaikin D, et al. The standardisation of terminology in nocturia: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002; 21(2): 179–83PubMedCrossRefGoogle Scholar
  21. 21.
    Millard RJ, Halaska M. Efficacy of solifenacin in patients with severe symptoms of overactive bladder: a pooled analysis. Curr Med Res Opin 2006 Jan; 22(1): 41–8PubMedCrossRefGoogle Scholar
  22. 22.
    Abrams P, Larsson G, Chapple C, et al. Factors involved in the success of antimuscarinic treatment. BJU Int 1999 Mar; 83Suppl. 2: 42–7PubMedGoogle Scholar
  23. 23.
    Meyhoff HH, Gerstenberg TC, Nordling J. Placebo —the drug of choice in female motor urge incontinence? Br J Urol 1983 Feb; 55(1): 34–7PubMedCrossRefGoogle Scholar
  24. 24.
    Khullar V, Chapple C, Gabriel Z, et al. The effects of antimuscarinics on health-related quality of life in overactive bladder: a systematic review and meta-analysis. Urology 2006 Aug; 68(Suppl. 2): 38–48PubMedCrossRefGoogle Scholar
  25. 25.
    Chapple CR, Rechberger T, Al-Shukri S, et al. Randomized, double-blind placebo-and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder. BJU Int 2004 Feb; 93(3): 303–10PubMedCrossRefGoogle Scholar
  26. 26.
    Michel MC, de la Rosette JJ. Role of muscarinic receptor antagonists in urgency and nocturia. BJU Int 2005 Sep; 96(Suppl. 1): 37–42PubMedCrossRefGoogle Scholar
  27. 27.
    Sandvik H, Seim A, Vanvik A, et al. A severity index for epidemiological surveys of female urinary incontinence: comparison with 48-hour pad-weighing tests. Neurourol Urodyn 2000; 19(2): 137–45PubMedCrossRefGoogle Scholar
  28. 28.
    Hanley J, Capewell A, Hagen S. Validity study of the severity index, a simple measure of urinary incontinence in women. BMJ 2001 May 5; 322(7294): 1096–7PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  • Steven E. Swift
    • 1
  • Paul Siami
    • 2
  • Sergio Forero-Schwanhaeuser
    • 3
  1. 1.Department of Obstetrics and GynecologyMedical University of South CarolinaCharlestonUSA
  2. 2.Deaconess ClinicEvansvilleUSA
  3. 3.GlaxoSmithKlineKing of PrussiaPennsylvaniaUSA

Personalised recommendations