Safety and Efficacy of SAF312 in Patients With Neurogenic Detrusor Overactivity Due to Spinal Cord Lesions

• Number of Participants with Adverse Events as a Measure of Safety [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
  Safety (physical exam, vital signs, haematology, coagulation parameters, clinical chemistry and urinalysis, ECG, pregnancy test, hand immersion test and PK [concentrations of SAF312 in blood]).
• Bladder threshold vol, threshold pressure, instilled vol at first leak, detrusor pressure at first leak, vol/detrusor pressure at first sensation and at first desire to void, maximum detrusor pressure during filling/storage, bladder wall compliance [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  All parameters examined during filling cystometry as measured by changes from baseline following treatment for one week
• Micturition or catheterization frequency [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  Changes from baseline, as measured by daily diaries.
• Incontinence episodes [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  Changes from baseline as measured by daily diaries.

• Number of Participants with Adverse Events as a Measure of Safety [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
  Safety (physical exam, vital signs, haematology, coagulation parameters, clinical chemistry and urinalysis, ECG, pregnancy test, hand immersion test and PK [concentrations of SAF312 in blood]).
• Bladder threshold volume [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  Bladder threshold volume, threshold pressure, instilled volume at first leak, detrusor pressure at first leak, volume/detrusor pressure at first sensation, volume/detrusor pressure at first desire to void, maximum detrusor pressure during filling/storage phase, bladder wall compliance
• Changes from baseline with respect to micturition or catheterization frequency as measured by daily diaries. [ Time Frame: 1 week ] [ Designated as safety issue: No ]
• Changes from baseline with respect to incontinence episodes as measured by daily diaries. [ Time Frame: 1 week ] [ Designated as safety issue: No ]

This study will assess the safety, tolerability and efficacy of SAF312 in patients with overactive bladder disease due to spinal cord lesions. The overactive bladder of patients who qualify for this study is insufficiently managed by antimuscarinic therapy, or patients poorly tolerate the treatment with antimuscarinic drugs. The efficacy of SAF312 will be primarily determined via urodynamic measurements.

• Neurogenic Urinary Bladder
• Neurogenic Bladder Disorder
• Neurogenic Dysfunction of the Urinary Bladder
• Neurogenic Bladder, Uninhibited
• Neurogenic Bladder, Spastic

• Drug: SAF312
  One week of treatment in a BID (two times a day) regimen (hard gelatin capsules for oral use)
• Drug: Placebo to SAF312
  One week of treatment in a BID (two times a day) regimen (hard gelatin capsules for oral use)

• Placebo Comparator: Placebo to SAF312
  Intervention: Drug: Placebo to SAF312
• Experimental: SAF312
  Intervention: Drug: SAF312

• Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, van Kerrebroeck P, Victor A, Wein A; Standardisation Sub-committee of the International Continence Society. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn. 2002;21(2):167-78.
• Schäfer W, Abrams P, Liao L, Mattiasson A, Pesce F, Spangberg A, Sterling AM, Zinner NR, van Kerrebroeck P; International Continence Society. Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn. 2002;21(3):261-74.

Inclusion Criteria:

• Patients with neurogenic detrusor overactivity due to spinal cord lesions
• Patients are inadequately managed by antimuscarinic medication and present with a cystometric bladder capacity of max. 400 mL

Exclusion Criteria:

• Chronic inflammation such as interstitial cystitis, bladder stones, hematuria of unknown origin, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs
• Pelvic or genitourinary tract anomalies including surgery or bladder disease other than detrusor overactivity impacting on bladder function