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

A Multi-center, Double-blind, Randomized, Placebo-controlled, Cross-over Study to Evaluate the Efficacy, Safety and Tolerability of SAF312 in Subjects With Neurogenic Detrusor Overactivity Due to Spinal Cord Lesions Who Are Inadequately Managed by Antimuscarinic Therapy

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.

Study Overview

• Status: Terminated
• Conditions: Neurogenic Urinary Bladder; Neurogenic Bladder Disorder; Neurogenic Dysfunction of the Urinary Bladder; Neurogenic Bladder, Uninhibited; Neurogenic Bladder, Spastic
• Intervention / Treatment: Drug: Placebo to SAF312; Drug: SAF312

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Murnau, Germany, D-82419
    • Novartis Investigative Site
• Netherlands
  • Nijmegen, Netherlands
    • Novartis Investigative Site
• Switzerland
  • Zürich, Switzerland, 8008
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo to SAF312	Drug: Placebo to SAF312; One week of treatment in a BID (two times a day) regimen (hard gelatin capsules for oral use)
EXPERIMENTAL: SAF312	Drug: SAF312; One week of treatment in a BID (two times a day) regimen (hard gelatin capsules for oral use)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum cystometric capacity (MCC)	Examined during filling cystometry as measured by changes from baseline following treatment for one week.	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety	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]).	1 week
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	All parameters examined during filling cystometry as measured by changes from baseline following treatment for one week	1 week
Micturition or catheterization frequency	Changes from baseline, as measured by daily diaries.	1 week
Incontinence episodes	Changes from baseline as measured by daily diaries.	1 week

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Stohrer M, Blok B, Castro-Diaz D, Chartier-Kastler E, Del Popolo G, Kramer G, Pannek J, Radziszewski P, Wyndaele JJ. EAU guidelines on neurogenic lower urinary tract dysfunction. Eur Urol. 2009 Jul;56(1):81-8. doi: 10.1016/j.eururo.2009.04.028. Epub 2009 Apr 21.
• 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. doi: 10.1002/nau.10052. No abstract available.
• Schafer 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. doi: 10.1002/nau.10066.

Helpful Links

• Results for CSAF312A2202 on the Novartis clinical trials website

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ACTUAL): September 1, 2012
• Study Completion (ACTUAL): September 1, 2012

Study Registration Dates

• First Submitted: February 17, 2012
• First Submitted That Met QC Criteria: May 14, 2012
• First Posted (ESTIMATE): May 15, 2012

Study Record Updates

• Last Update Posted (ACTUAL): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: spinal cord injury; Neurogenic detrusor overactivity; spinal cord lesions
• Additional Relevant MeSH Terms: Nervous System Diseases; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Neurologic Manifestations; Urinary Bladder, Overactive; Urinary Bladder, Neurogenic; Urinary Bladder Diseases
• Other Study ID Numbers: CSAF312A2202; 2010-021137-32 (EUDRACT_NUMBER)