Primary: effects of SAF312 on the Maximum Cystometric Capacity (changes from baseline) versus placebo following one-week treatment.Secondary: Evaluation of the safety, tolerability and PK, PK/PD, additional parameters examined during cystometry,…
ID
Source
Brief title
Condition
- Bladder and bladder neck disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Maximal Cystometric Capacity.
Secondary outcome
Adverse events, PK, PD, additional parameters examined during cystometry,
micturition or catheterization frequency, incontinence episodes.
Background summary
This study is designed as a proof of efficacy of SAF312 in neurogenic detrusor
overactivity. SAF312, a low molecular weight compound, is an orally active
potent and selective inhibitor of human TRPV1 (vanilloid receptor 1) channels.
TRPV1 channels are sensitized in conditions involving inflammation and tissue
or nerve damage. Their engagement can lead to peripheral sensitization to
physiological stimuli resulting in hyperalgesia and hypersensitivity conditions.
The study will assess whether or not SAF312 through inhibition of TRPV1 can
provide clinical benefit to subjects presenting with neurogenic detrusor
overactivity due to spinal cord lesions who are inadequately managed by
antimuscarinic therapy.
The present study will measure the urodynamic as well as clinical response to
repeated administrations of SAF312 for 1 week. Moreover, the study will provide
safety and tolerability data in this subject population. The study may proceed
(sequentially) with testing SAF312 at a lower dose strength in another group of
subjects pending analyses of efficacy, safety and tolerability at the first
dose level.
Study objective
Primary: effects of SAF312 on the Maximum Cystometric Capacity (changes from
baseline) versus placebo following one-week treatment.
Secondary: Evaluation of the safety, tolerability and PK, PK/PD, additional
parameters examined during cystometry, micturition or catheterization
frequency, incontinence episodes.
Study design
Multicenter randomized double blind placebo controlled cross-over study.
Randomization (1:1) to treatment sequence with:
• SAF312 25 mg bid during 1 week
• Washout period of at least 1 week
• Placebo bid during 1 week.
of
• Placebo bid during 1 week
• Washout period of at least 1 week
• SAF312 25 mg bid during 1 week.
Screening period of max. 3 weeks. Baseline period 1 week. Final visit within 1
week after the end of study treatment.
Interim-analysis planned after 18 patients. Option to amend protocol
(assessment of lower dose).
Max. 36 patients.
Intervention
Treatment with SAF312 and placebo.
Study burden and risks
Risk: Adverse effects of study medication and possible infection due to
cystometry. Possible consequences of discontinuation of prescribed medication 4
weeks prior to treatment period.
Burden: Study duration approx. 8 weeks. 8 visits. Duration 2-24 h, there off 4
visits of 24 h.
Physical examination 5 times.
Blood draw during 7 visits, 10-45 ml per occasion and approx. 200 ml in total.
Optional pharmacogenetic blood testing (10 ml).
Pregnancy test (if relevant) 4 times.
ECG 9 times (there off 4x at 2 time points).
Hot water test (Hand immersion at 49°C) 5 times. Based on the results during
study medication, prolongation of the hospital stay may be indicated.
Cystometry 3 times.
Daily measurement of body temperature.
After the end of the screening until the end of treatment phase 1 and during
treatment phase 2 a diary should be kept on days not spent in the hospital. 2
times a day a number of questions in an SMS message should be answered about
incontinence and self catheterization, use of study medication and the body
temperature measured.
Raapopseweg 1
6814 DP Arnhem
NL
Raapopseweg 1
6814 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
• Males and females 18-65 years of age with an established diagnosis of Neurogenic Detrusor overactivity as result of a spinal cord lesions with complete or incomplete lesions that have occurred at least 6 months prior to screening.
• Subjects must have not been adequately managed through antimuscarinic therapy prior to screening. Inadequate management: see protocol for details.
• For subjects taking antimuscarinics with good tolerability, the dose is stable and subjects are willing to maintain the same dose during study participation.
• For subjects with intolerable side-effects associated with antimuscarinic therapy, dosing of antimuscarinics must end at least 1 week prior to the onset of the baseline period.
• Subjects use or are willing to use Intermittent Catheterization (IC) throughout the study.
• Subjects are willing to take an antibiotic medication prophylactically at each of the three cystometries.
Exclusion criteria
• Subjects with evidence of 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.
• Subjects with a history or evidence of any pelvic or genitourinary tract anomalies that may impact on bladder function with the exception of bladder stones (>6 months ago) and stress incontinence, uterine prolapse, rectocele, or cystocele (>1 year ago) from screening.
• Subjects with an acute urinary tract infection.
• Use of other treatment intended to treat overactive bladder symptoms including electrostimulation therapy, botulinum toxin, capsaicin and/or resiniferatoxin therapy in the six (6) months prior to the commencement of the study.
• Use of antidepressants or muscle relaxants which have not been administered at a constant dose for at least 1 month prior to the commencement of the study.
• Subjects not able to perform the hand immersion test at Baseline 1. This only applies to subjects who present with a non-impaired skin thermal perception of at least one hand; subjects with sensitivity disturbances of their hands will not be tested.
• Subjects who undergo the hand immersion test and keep one hand in the water bath at 49°C for >= 1 minute (no painful sensation during this time period) at first baseline.
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 |
|---|---|
| Other | clinicaltrials.gov, registratienummer n.n.b. |
| EudraCT | EUCTR2010-021137-32-NL |
| CCMO | NL38543.091.11 |