The aim of the study is to assess the efficacy and safety of intra - detrusor injections of Dysport versus placebo in subjects suffering from neurogenic detrusor overactivity following spinal cord injury or multiple sclerosis.

• Register: EUCTR
• Last refreshed on: 30 June 2014
• Main ID: EUCTR2010-023210-31-DE
• Date of registration: 09/11/2011
• Prospective Registration: Yes
• Primary sponsor: Ipsen Innovation
• Public title: The aim of the study is to assess the efficacy and safety of intra - detrusor injections of Dysport versus placebo in subjects suffering from neurogenic detrusor overactivity following spinal cord injury or multiple sclerosis.
• Scientific title: A PHASE IIA, MULTICENTRE, DOUBLE BLIND, SINGLE DOSE, PARALLEL GROUP, PLACEBO CONTROLLED, CLINICAL PILOT STUDY TO ASSESS THE EFFICACY AND SAFETY OF SINGLE DOSE, INTRA-DETRUSOR INJECTIONS OF 750 UNITS OF DYSPORT IN SUBJECTS SUFFERING FROM NEUROGENIC DETRUSOR OVERACTIVITY FOLLOWING SPINAL CORD INJURY OR MULTIPLE SCLEROSIS
• Date of first enrolment: 24/02/2012
• Target sample size: 42
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023210-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Austria, Czech Republic, Germany, Italy, Lithuania

Contacts

• Name: Clinical Operations
• Affiliation: Ipsen Innovation

• Name: Clinical Operations
• Affiliation: Ipsen Innovation

Key inclusion & exclusion criteria

Inclusion criteria:
(10 Written informed consent prior to any study related procedures.
(2) Male or female subjects aged 18 to 70, inclusive.
(3) Urinary incontinence as a result of NDO due to documented SCI or MS as defined by the ICS guidelines.
(4) Inadequate response or refractory to anticholinergic medication used to treat neurogenic overactive bladder.
(5) The dose and class of anticholinergic treatment, if any, must be fixed for the duration of the study and stable at randomisation visit.
(6a) Have documented SCI or MS (both complete and incomplete SCIs and relevant MS with confirmed NDO as defined by ICS guidelines will be included in this study).
(7) Have documented urinary tract exploration at screening. If not, lower urinary tract echography shall be conducted prior to baseline.
(8) Have a minimum average of two incontinence episodes per day calculated as the average daily IEF over the 3 days preceding the baseline visit (three consecutive 24 hour periods).
(9) Subject, family member or care giver is willing and able to perform CIC for the duration of the study.
(10) Have an exclusive and well trained voiding mode by clean self
catheterisation before baseline.
(11) Be able to complete all study requirements including completing a daily voiding diary and to attend all scheduled study visits, in the opinion of the Investigator.
(12a) Female subjects of child-bearing potential must have a negative pregnancy test result and be willing to use reliable contraceptive measures for the duration of the study (i.e. oral contraceptives and spermicide, when used in combination with condoms, etc as a ‘double barrier method’).
(13) Botulinum toxin naïve for intra-detrusor injections and have no previous treatment with BTX of any type, within 3 months prior to study entry for any other condition.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion criteria:
(1) Greater than 3 L diuresis per day based on the average over the 3 days preceding the baseline visit (three consecutive 24 hour periods).
(2a) Previous or current diagnosis of bladder disease and urethral disease or surgery, or prostate cancer (prostate specific antigen of >10 ng/mL).
Subjects with serum prostate specific antigen concentrations >4 ng/mL and <10 ng/mL must have prostate cancer excluded.
(3) Clinical symptomatic urinary tract infection at screening visit without adapted antibiotherapy.
(4) History of NDO due to an aetiology other than SCI or MS.
(5) History of stress incontinence.
(6) Significant baseline renal and/or urinary tract pathology
(e.g. hydronephrosis, stones, renal mass) at screening.
(7) History of unexplained haematuria.
(8) Known history of interstitial cystitis, uninvestigated haematuria,
mullerian duct cysts, and urethral obstruction due to
stricture/valves/sclerosis of urethral tumour, radiation cystitis, genitorurinary tuberculosis, or bladder calculi.
(9) Current indwelling catheter, or removal of chronic catheter <1 month prior to randomisation visit.
(10) Any medical condition that may increase their risk of exposure to BTX including diagnosed myasthenia gravis, Lambert-Eaton Syndrome, amyotrophic lateral sclerosis or any other disease that might interfere with neuromuscular function.
(11) Any condition or situation which, in the Investigator's opinion, puts the subject at significant risk, may confound the study results, or may significantly interfere with the subject's participation in the study.
(12) History of allergy or intolerance to local anaesthetics (lidocaine, xylocaine etc).
(13) History of chronic drug or alcohol abuse.
(14) Previous treatment with any endovesical pharmacologic agent including detrusor BTX injection.
(15) Have previously undergone urethral stent placement or sphincterotomy.
(16) Use of medications with anti-platelet or anticoagulant effects (except Low Molecular Weight Heparin) within 10 days of randomisation. (Low Molecular Weight Heparin is standard of care after SCI until 2 to 3 months post injury; for post SCI subjects it will be stopped 24 hours before and for 48 hours after each bladder injection).
(17) Use of medications that affect neuromuscular transmission, such as curare-like depolarising agents, lincosamides, polymyxins,
anticholinesterases and aminoglycoside antibiotics.
(18) Concurrent therapy which, in the Investigator's opinion, would interfere with the evaluation of study medication safety or efficacy.
(19) Receipt of any experimental drug or use of any experimental device within 30 days prior to the screening visit.
(20) Nursing or lactating female subjects.
(21) Known hypersensitivity to botulinum toxin (BTX) or to any components in the study drug formulation (including cow’s milk protein).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

NEUROGENIC DETRUSOR OVERACTIVITY
MedDRA version: 15.1 Level: LLT Classification code 10012547 Term: Detrusor hyperreflexia System Organ Class: 100000004857

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Dysport
Product Name: Dysport
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CLOSTRIDIUM BOTULINUM TOXIN TYPE A
CAS Number: 93384-43-1
Other descriptive name: BOTULINUM TOXIN TYPE A
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Secondary Objective: The secondary study objective is to assess the change over time in urodynamic parameters (manocystometric measurements according to the 'Good Urodynamic Practice' of the ICS) quality of life, catheterisations and the response to treatment following treatment with a single dose of Dysport (750 U) compared to placebo for each administration mode (15 or 30 injection sites), as well as the pain induced by the injection procedure.

Primary end point(s): Mean change from baseline in the averaged daily frequency of episodes of urinary incontinence (calculated as the average daily IEF over the 3 days preceding each visit).

Main Objective: The primary study objective is to assess the efficacy of a single dose of Dysport (750 U) compared to placebo for the improvement in the daily incontinence episode frequency (IEF) for each administration mode (15 or 30 injection sites).

Timepoint(s) of evaluation of this end point: to Day 84

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - Urodynamic examination / Quality of Life assessment / Clean self catheterisations per day / Physician's global assessment : Day 14, Day 42 and Day 84

- Pain: prior to and after the cystoscopic intra-detrusor
injection of study treatment (at baseline)

Secondary end point(s): - Urodynamic examination: manocystometric measurements.
- Quality of Life assessment.
- Pain prior to and after administration of study treatment.
- Clean self catheterisations per day.
- Physician's global assessment of the treatment response as
compared with baseline.

Secondary ID(s)

Y52-52120-155

Source(s) of Monetary Support

Ipsen Innovation