A placebo-controlled, randomized, safety and efficacy study of BOTOX® (Bolulinum Toxin Type A) Purified Neurotoxin Complex in patients with neurogenic detrusor overactivity and neurological respiratory impairment.
- Conditions
- Neurogenic Overactive Bladder: urine incontinence due to illness or damage of the spinal cord1004154310038716
- Registration Number
- NL-OMON31185
- Lead Sponsor
- Allergan
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 5
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 due to spinal cord injury or multiple sclerosis, 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 score between 7.0 and 8.0, inclusively.
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 withing 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 Day -1) or Randomization/Day -1.
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.
15. Both multiple sclerosis (MS) and spinal cord injury (SCI) patients must be willing to use intermittent catherization (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 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.
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.
3. Patient has history or evidence of any significant pelvic or urological abnormality, including, but not limited to, the following:
* elevated serum creatinin > 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)
6. Patient has discontinued anticholinergic medication for the treatment of overactive bladder <21 days prior to Randomization/Day1.
7. Patient has an untreated or symptomatic (e.g. fever, recent change in neurological status) urinary tract infection (UTI) on Randomization/Day 1.
10. Patient has an acute respiratory tract infection. 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 chest X-ray (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 a history of, or acute exacerbation of COPD within 3 months prior to Screening Day -21.
15. Patient has 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 wihin 12 months prior to Screening Day -21.
17. Patient requires supplemental oxygen and/or ventilatory support.
18. Patient has evidence of carbon dioxide (CO2) retention as indicated by a serum bicarbonate level greater than the upper limit of the normal (reference range) at Screening Day -21.
19. Patient has used any antiplatelet or anticoagulant therapy or is using medications with anticoagulative effects within 3 days prior to treatment. Some medications may need to be withheld for > 3 days per clinical judgement of the investigator (refer to Section 8.2.2 Prohibited Medications/Treatments for details).
21. Patient is currently using, or plans to use, an implanted or non-implantable electrostimulation/neuromodulation device for treatment of overactive bladder.
22. Patient is currently being treated with an intrathecal baclofen pump.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety measures are the primary study parameters:<br /><br><br /><br>Primary safety measures:<br /><br>* Forced Vital Capacity (FVC) (percent predicted and absolute value)<br /><br>* Forced Expiratory Volume (FEV1) (percent predicted and absolute value)<br /><br>* Oxyhemoglobin Saturation<br /><br>* Maximum Inspiratory Pressure (MIP)<br /><br>* Maximum Expiratory Pressure (MEP)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary safety measures:<br /><br>* Serious Medical Events<br /><br>* Adverse Events<br /><br>* Physical Examination<br /><br>* Vital signs<br /><br>* Hematology and non-fasting chemistry<br /><br>* Urinalysis<br /><br>* Bladder and kidney ultrasound<br /><br>* Post void residual<br /><br><br /><br>Secondary efficacy measures:<br /><br>* Number of episodes of urinary incontinence as recorded in the patient bladder<br /><br>diary<br /><br>* Number of episodes voided as recorded in the patient bladder diary<br /><br>* Urodynamic parameters</p><br>