Primary Objective: To assess the effect of treatment with three doses of botulinum toxin type-A (Dysport®) versus placebo on the number of episodes of urgency and frequency of micturition experienced in continent female subjects with idiopathic…
Source
Brief title
Condition
- Bladder and bladder neck disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
Percent change in the cumulative number of episodes of urgency and frequency
recorded during the three day period immediately prior to the Week 12 or early
termination princeps study visit compared to the three day period prior to the
Baseline visit.
Secondary outcome
Percent change in the cumulative number of episodes of urgency, frequency and
nocturia recorded during the three day period immediately prior to Week 6 visit
compared to the three day period prior to the Baseline visit.
Percentage of normalized subjects, responder subjects (25% improvement of their
symptoms) and subjects reporting no incidence of urgencies at week 6, at week
12 or princeps early termination visit.
Change in the average severity of urgency, change in maximum flow rate test and
PMRV, change in urodynamic parameters, change in quality of life and the
duration of the effect of treatment will be evaluated.
Background summary
OAB is a highly prevalent condition and the treatment needs to be optimized.
Previous publications show that BoNT-A is effective to improve the urinary
symptoms of OAB (including urgency and frequency), incontinence and the
urodynamic parameters. Safety issues (transient muscular weakness and transient
urinary retention) seem to be dose-related.
Large, dose ranging, double blind, placebo controlled studies are needed to
validate these encouraging preliminary data.
Study objective
Primary Objective: To assess the effect of treatment with three doses of
botulinum toxin type-A (Dysport®) versus placebo on the number of episodes of
urgency and frequency of micturition experienced in continent female subjects
with idiopathic overactive bladder (iOAB) at Week 12 in comparison to Baseline.
Secondary Objectives: To assess the effect of three doses of Dysport® versus
placebo on the number of episodes of urgency, frequency of micturition, and
frequency of nocturia at all assessment timepoints compared to Baseline. To
assess the severity of urgency. To assess the effect on maximum flow rate and
post-micturition residual volume (PMRV) at Day 4 and Week 6. To assess the
effect on standard ICS urodynamic parameters and on the quality of life. To
evaluate the safety and the duration of treatment.
Study design
Three doses of botulinum toxin type-A (Dysport®) (125, 250 and 500 U) will be
compared versus placebo. 301 Patients who fulfill all inclusion/exclusion
criteria will be randomized in 4 treatment arms: 125 units, 250 units, 500
units or placebo following a 1, 2, 2, 2 allocation respectively.
The study contains 3 phases:
• A (maximum) 28 days Screening phase.
• A 12-week, double-blind, randomised, placebo-controlled Princeps phase. The
Latin word Princeps means * the first* and is used to differentiate the 12-week
phase from the optional 6-month extension phase.
• An optional 6-month extension phase. Subjects whose symptoms at 12 weeks show
more than 25% improvement from baseline will be invited to enter the 6-month
extension phase.
Intervention
The IMP (either Dysport® or placebo) will be administrated in an outpatient
setting under local anaesthetic using a rigid cystoscope. The IMP will be
slowly injected over 16 standardized sites in the detrusor muscle of the
bladder with an antibiotic prophylaxis, according to local routine practice
(except aminoglysosides).
Study burden and risks
In the unlikely event that the injected treatment diffuses outside of the
bladder, temporary weakness/paralysis of nearby muscles may occur but this
usually resolves in a few weeks.
Allergic reactions e.g. skin rashes and flu-like symptoms have occasionally
been reported.
In a small number of subjects, Botulinum toxin type A can stop working after a
number of treatments. This may be because the immune system produces antibodies
to inactivate the medicine. Because of the temporary paralysis of the bladder,
you could need to empty yourself your bladder. That is why you could be trained
by the research doctor*s team on when and how to use a urinary catheter. Local
events (e.g. pain, urinary infection, and bleeding) could occur due to the
procedure and not to injected treatment.
The patient need to attend the hospital/clinic for a maximum of 7 visits during
10 months. It is a single injection cycle at Baseline visit. The urodynamic
assessments will occur during screening and at visit 5 (approximatly 14 weeks
after screening).
Nederland
Nederland
Listed location countries
Age
Inclusion criteria
• The subject has given written informed consent to participate in the 2 phases of the study.
• The subject is female and aged between 18 and 75 years.
• The subject has a diagnosis of idiopathic overactive bladder, without incontinence.
• The subject has > 3 urgency episodes over the course of the 3 days immediately preceding the Baseline visit.
• The subject has > 24 episodes of micturition over the course of the 3 days immediately preceding the Baseline visit.
• The subject has failed to respond sufficiently to oral anticholinergics, or is unable to tolerate anticholinergics, as determined by the treating physician.
• If the subject is taking anticholinergics she must be willing to discontinue their use at screening (2 weeks before the first urodynamic investigation) and refrain from taking them for the duration of the study.
• The subject is able and willing to complete questionnaires and maintain accurate records on the eDiary.
• The subject is willing and physically able to perform ISC should it be necessary following treatment with the investigational medicinal product.
Exclusion criteria
• Subject with a PMRV > 150 ml (ultrasound assessment).
• The subject has evidence of a urinary tract infection at Screening or Baseline in the study (detection by midstream urine dipstick analysis).
• The subject has active or history of interstitial cystitis, malignancy of the bladder or urothelial tract, a carcinoma in situ (non malignant melanoma is allowed) bladder and/or kidney stones, or a history of any of the above.
• The subject is at risk of pregnancy or lactation during the study. Females of childbearing potential must provide a negative pregnancy test at baseline (visit 2) prior to administration of study medication and must be using oral, double barrier (e.g., diaphragm with spermicide; or male condom and diaphragm) or injectable contraception. Non childbearing potential is defined as post-menopause for at least 1 year, surgical sterilisation or hysterectomy at least three months before the start of the study.
• The subject has overactive bladder due to spinal cord injury, multiple sclerosis or other neurogenic cause (e.g. Parkinson*s disease).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | 2007-002999-34-NL |
CCMO | NL19701.091.07 |