A Placebo-Controlled, Randomized, Safety and Efficacy Study of BOTOX® (Botulinum Toxin Type A) Purified Neurotoxin Complex in Patients with Neurogenic Detrusor Overactivity and Neurological Respiratory Impairment
- Conditions
- Patients with urinary incontinence due to neurogenic detrusor overactivity as a result of spinal cord injury or multiple sclerosis who have not been adequately managed with anticholinergic therapy and have neurological respiratory impairment.MedDRA version: 8.1Level: LLTClassification code 10046543Term: Urinary incontinence
- Registration Number
- EUCTR2006-006299-39-NL
- Lead Sponsor
- Allergan
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 135
1. Patient is male or female, aged 18 to 80 years old.
2. Patient weighs = 50 kg (110 lbs).
3. Written informed consent has been obtained.
4. Written Authorization for Use and Release of Health and Research Study Information (US sites only) has been obtained.
5. Written Data Protection Consent (European sites only) has been obtained.
6. Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable.
7. Patient has urinary incontinence as a result of neurogenic detrusor overactivity for a period of at least 3 months prior to Screening Day -21 as a result of spinal cord injury (SCI) or multiple sclerosis (MS), determined by documented patient history. In addition:
• Spinal cord injured patients must have a stable neurological injury between cervical level 5 (C5) and cervical level 8 (C8), inclusively as determined by the neurological definition of SCI; complete or incomplete. The spinal cord injury must have occurred = 12 months prior to Screening Day -21.
• Multiple sclerosis patients must be clinically stable, in the investigator’s opinion, for = 3 months prior to Screening and through Randomization/Day 1. Patients must have an Expanded Disability Status Scale (EDSS) score between 7.0 and 8.0, inclusively.
8. Patient has the ability to perform acceptable and reproducible pulmonary function testing as determined by the investigator and pulmonologist.
9. Patient has a Forced Vital Capacity (FVC) between 50% and 80% of predicted value on two separate testing days during Screening (Day -21 to Day -1). Note: The difference between the largest FVC observed on each testing day must not exceed 20%. There should be at least 7 days between the two screening PFTs and the second PFT must occur within 0-5 days prior to Randomization/Day 1 Visit.
10. Patient has detrusor overactivity (defined as a phasic rise in bladder pressure during the filling phase as determined by urodynamics) demonstrated during the Screening period (Day -21 to -1) ) or Randomization/Day 1.
11. Patient is able to complete study requirements and attend all study visits (telephone and clinic), in the opinion of the investigator.
12. Patient has not been adequately managed with one or more anticholinergics for their urinary incontinence, in the opinion of the investigator. Not adequately managed” is defined as an inadequate response to or intolerable side effects while taking an optimized dose for at least one month.
13. For patients taking anticholinergic medication for their neurogenic overactive bladder, dose is stable and patient is willing to maintain same dosing during study participation.
14. Patient has a negative pregnancy test result if female and of childbearing potential.
15. Both MS and SCI patients must be willing to use IC to empty the bladder and maintain an established catheterization frequency throughout the study. Caregiver may perform IC for patient, if patient is unable to do this. (Indwelling catheters and suprapubic catheters are not permitted).
16. Patient experiences = 4 episodes of urinary incontinence (leakage) over 3 days determined by completion of a bladder diary during the Screening period.
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) yes
F.1.3.1 Number of subjects for this age range
1. Patient has had previous or current botulinum toxin therapy of any serotype for any urological condition or treatment within 3 months of Randomization/Day 1 for any other condition
2. Patient has been immunized for any botulinum toxin serotype.
3. Patient has history or evidence of any significant pelvic or urological abnormality including but not limited to the following (described in protocol):
- elevated serum creatinine >2 times the upper limit of normal (reference range)
- history of or current hematuria, 1) if the hematuria is determined to be due to a - pathologic condition or 2) is uninvestigated.
- interstitial cystitis in the opinion of the investigator
- bladder stones within 6 months of Screening Day - 21
- surgery or bladder disease other than detrusor overactivity that may impact bladder function with the exception of surgeries for bladder stones (> 6 months) and stress incontinence, uterine prolapse, rectocele, or cystocele (> 1 year from Screening Day -21)
4. Patient is male with previous or current diagnosis of prostate cancer. Patients with a PSA level greater than 4.0 ng/mL at Screening Day -21 will require a biopsy to rule out prostate cancer, unless a prostatic biopsy has been performed within the past 12 months.
5. Patient has a history or current diagnosis of bladder cancer or has urine cytology results which may indicate bladder cancer, not ruled out by the investigator at Randomization/Day 1. Suspicious urine cytology abnormalities require the investigator’s assessment that the findings are not indicative of malignancy.
6. Patient has discontinued anticholinergic medication for the treatment of overactive bladder < 21 days prior to Randomization/Day 1.
7. Patient has an untreated or symptomatic (e.g. fever, recent change in neurological status) urinary tract infection (UTI) on Randomization/Day 1.
8. Patient has a post void residual volume above 150 mL for patients who micturate or have a mixed catheterization/spontaneous micturition pattern.
9. Patient has an active genital infection, other than genital warts, within 4 weeks prior to Screening Day -21.
10. Patient has an acute respiratory tract infection at during (Screening Day -21 to Day -1) or Randomization/Day 1. Patient may qualify for re-screening upon clinical resolution and stabilization (one month, or longer based on the investigator’s opinion, has elapsed after clinical resolution without recurrent symptoms).
11. Patient has a clinically significant abnormal CXR finding. Patient may qualify for re-screening upon resolution, or the CXR finding is no longer considered clinically significant.
12. Patient has clinically significant intrinsic lung disease (e.g. sarcoidosis, pulmonary fibrosis, bronchiectasis).
13. Asthmatics, whose disease is not stable (i.e., have had exacerbation(s) of asthma within 3 months prior to Screening Day -21). Note: Stable, preventative respiratory medications/therapy are permitted.
14. Patient has an acute exacerbation of COPD within 3 months prior to Screening Day -21.
15. Patient has had a pulmonary embolus (PE) within 6 months of Screening Day -21, or a history of recurrent pulmonary emboli (i.e., a diagnosis of PE on more than one occasion per lifetime).
16. Patient has aspiration pneumonia, aspiration pneumonitis or acute respiratory failure within 12 months prior to Screening Day -21.
17. Patient requires supplemental oxygen and/or ventilatory support.
18. Patient has evidence of carbon dioxi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: ;Main Objective: To evaluate the safety and efficacy of 2 dose levels of BOTOX® (200 U or 300 U) compared to placebo injected into the detrusor for the treatment of urinary incontinence caused by neurogenic detrusor overactivity in patients who have not been adequately managed with anticholinergic therapy and have neurological respiratory impairment.;Primary end point(s): • Number of episodes of urinary incontinence as recorded in the patient bladder diary <br>• Number of episodes of voiding and method (catheterization or voluntary) as recorded in the patient bladder diary <br>• Urodynamic parameters, as detailed in the protocol. Urodynamic studies will be conducted according to International Continence Society (ICS) standard guidelines (Homma et al, 2002) and results will be assessed by an independent central urodynamic reviewer.
- Secondary Outcome Measures
Name Time Method