Clinical trial NCT00432666: IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Post-stroke Spasticity of the Upper Limb
Official title: Prospective, Double-blind, Placebo-controlled, Randomized, Multi-center Trial With an Open-label Extension Period to Investigate the Efficacy and Safety of incobotulinumtoxinA (Xeomin) in the Treatment of Post-stroke Spasticity of the Upper Limb
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-stroke Upper Limb Spasticity
Lead sponsor: Merz Pharmaceuticals GmbH
Sponsor class: INDUSTRY
First posted: 2007-02-08
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: IncobotulinumtoxinA (Xeomin) is a botulinum toxin type A preparation free from complexing proteins, i.e. free from proteins other than the active toxin. Injected into the muscle, incobotulinumtoxinA (Xeomin) causes local weakening. Botulinum toxin type A is widely used for treatment of various neurological conditions. This study will investigate the efficacy and safety of incobotulinumtoxinA (Xeomin) in the treatment of post-stroke spasticity of the upper limb.


Eligibility criteria: Main Inclusion Criteria:

* Female or male patients ≥ 18 years
* ≥ 6 months since the last stroke, diagnosed by an appropriate health care professional (e.g., neurologist)
* Focal spasticity with ≥ 2 points on the Ashworth Scale in the wrist flexors with clinical pattern Flexed Wrist
* Focal spasticity with ≥ 2 points on the Ashworth Scale in the fingers flexors with clinical pattern Clenched Fist
* For pre-treated patients only: source documentation of the most recent injection session with Botulinum Toxin and sufficient therapeutic response for Flexed Wrist and Clenched Fist
* For pre-treated patients only: the most recent injection with Botulinum Toxin must have been maximal 50 Units BOTOX® or 200 Units Dysport® or 2000 Units Neurobloc® (type B preparation) per each of these flexors: carpi ulnaris, digitorum superficialis, digitorum profundus
* For pre-treated patients only: the most recent injection with Botulinum Toxin must have been maximal 60 Units BOTOX® or 240 Units Dysport® or 2400 Units Neurobloc® (type B preparation) for flexor carpi radialis

Main Exclusion Criteria:

* Spasticity of any other origin than stroke
* Previous treatment with Botulinum Toxin of any serotype and for any body region within the 4 months prior to Screening (Visit 1, Day -7)
* Planned concomitant treatment with Botulinum Toxin of any serotype and for any body region
* Previous or planned treatment with phenol- or alcohol-injection in the target limb
* Previous surgical treatment of spasticity in the target muscle(s)
* Fixed contracture, defined as severe restriction of the range of joint movement on passive stretch
* Severe atrophy of the target limb muscles

Primary outcomes:
measure: Number of Participants With Reduction of at Least 1 Point at Week 4 Compared to Baseline in Ashworth Score in Wrist Flexors
timeFrame: Baseline, Week 4
Secondary outcomes:
measure: Responders at Week 4 Based on a Responder Definition of at Least 2 Points Improvement From Baseline in the Ashworth Score for Wrist Flexors
timeFrame: Baseline, Week 4
measure: Responders Based on a Responder Definition of at Least 1 Point Improvement From Baseline in the Ashworth Score for Wrist Flexors at All Other Post Baseline Visits
timeFrame: Baseline, Week 2, Week 8, Week 12, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Responders Based on a Responder Definition of at Least 1 Point Improvement From Baseline in the Ashworth Score for Treated Elbow Flexors at All Post Baseline Visits
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Responders Based on a Responder Definition of at Least 1 Point Improvement From Baseline in the Ashworth Score for Treated Forearm Pronators at All Post Baseline Visits
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Responders Based on a Responder Definition of at Least 1 Point Improvement From Baseline in the Ashworth Score for Treated Finger Flexors at All Post Baseline Visits
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Responders Based on a Responder Definition of at Least 1 Point Improvement From Baseline in the Ashworth Score for Treated Thumb Flexors at All Post Baseline Visits
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 2 in Ashworth Scale Score for Treated Elbow Flexors
timeFrame: Baseline, Week 2
measure: Change From Baseline to Week 4 in Ashworth Scale Score for Treated Elbow Flexors
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 8 in Ashworth Scale Score for Treated Elbow Flexors
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 12 in Ashworth Scale Score for Treated Elbow Flexors
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in Ashworth Scale Score for Treated Elbow Flexors
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 2 in Ashworth Scale Score for Treated Forearm Pronators
timeFrame: Baseline, Week 2
measure: Change From Baseline to Week 4 in Ashworth Scale Score for Treated Forearm Pronators
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 8 in Ashworth Scale Score for Treated Forearm Pronators
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 12 in Ashworth Scale Score for Treated Forearm Pronators
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in Ashworth Scale Score for Treated Forearm Pronators
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 2 in Ashworth Scale Score for Wrist Flexors
timeFrame: Baseline, Week 2
measure: Change From Baseline to Week 4 in Ashworth Scale Score for Wrist Flexors
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 8 in Ashworth Scale Score for Wrist Flexors
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 12 in Ashworth Scale Score for Wrist Flexors
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in Ashworth Scale Score for Wrist Flexors
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 2 in Ashworth Scale Score for Finger Flexors
timeFrame: Baseline, Week 2
measure: Change From Baseline to Week 4 in Ashworth Scale Score for Finger Flexors
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 8 in Ashworth Scale Score for Finger Flexors
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 12 in Ashworth Scale Score for Finger Flexors
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in Ashworth Scale Score for Finger Flexors
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 2 in Ashworth Scale Score for Treated Thumb Flexors
timeFrame: Baseline, Week 2
measure: Change From Baseline to Week 4 in Ashworth Scale Score for Treated Thumb Flexors
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 8 in Ashworth Scale Score for Treated Thumb Flexors
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 12 in Ashworth Scale Score for Treated Thumb Flexors
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in Ashworth Scale Score for Treated Thumb Flexors
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Time to Onset of Treatment Effect
timeFrame: Period starting at Visit 2 (baseline injection) of the Main Period up to onset of treatment effect
measure: Time to Waning of Treatment Effect
timeFrame: Defined as time (weeks) from Visit 2 (injection session at Baseline, Day 0) to the subjective estimation of the waning of the effect
measure: Duration of Treatment Effect
timeFrame: Period from the day of injection until the time point of a need for a new injection agreed by the patient and the investigator
measure: Investigator's Global Assessment of Efficacy
timeFrame: Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Patient's Global Assessment of Efficacy
timeFrame: Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Carer's Global Assessment of Efficacy
timeFrame: Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 2 in the Disability Assessment Scale for the Principal Therapeutic Target
timeFrame: Baseline, Week 2
measure: Change From Baseline to Week 4 in the Disability Assessment Scale for the Principal Therapeutic Target
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 8 in the Disability Assessment Scale for the Principal Therapeutic Target
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 12 in the Disability Assessment Scale for the Principal Therapeutic Target
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in the Disability Assessment Scale for the Principal Therapeutic Target
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 2 in the Disability Assessment Scale for Domain "Hygiene"
timeFrame: Baseline, Week 2
measure: Change From Baseline to Week 4 in the Disability Assessment Scale for Domain "Hygiene"
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 8 in the Disability Assessment Scale for Domain "Hygiene"
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 12 in the Disability Assessment Scale for Domain "Hygiene"
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in the Disability Assessment Scale for Domain "Hygiene"
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 2 in the Disability Assessment Scale for Domain "Dressing"
timeFrame: Baseline, Week 2
measure: Change From Baseline to Week 4 in the Disability Assessment Scale for Domain "Dressing"
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 8 in the Disability Assessment Scale for Domain "Dressing"
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 12 in the Disability Assessment Scale for Domain "Dressing"
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in the Disability Assessment Scale for Domain "Dressing"
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 2 in the Disability Assessment Scale for Domain "Limb Position"
timeFrame: Baseline, Week 2
measure: Change From Baseline to Week 4 in the Disability Assessment Scale for Domain "Limb Position"
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 8 in the Disability Assessment Scale for Domain "Limb Position"
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 12 in the Disability Assessment Scale for Domain "Limb Position"
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in the Disability Assessment Scale for Domain "Limb Position"
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 2 in the Disability Assessment Scale for Domain "Pain"
timeFrame: Baseline, Week 2
measure: Change From Baseline to Week 4 in the Disability Assessment Scale for Domain "Pain"
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 8 in the Disability Assessment Scale for Domain "Pain"
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 12 in the Disability Assessment Scale for Domain "Pain"
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in the Disability Assessment Scale for Domain "Pain"
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 4 in the Carer Burden Scale for Domain "Cleaning the Palm of the Affected Hand"
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 12 in the Carer Burden Scale for Domain "Cleaning the Palm of the Affected Hand"
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in the Carer Burden Scale for Domain "Cleaning the Palm of the Affected Hand"
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 4 in the Carer Burden Scale for Domain "Cutting the Fingernails of the Affected Hand"
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 12 in the Carer Burden Scale for Domain "Cutting the Fingernails of the Affected Hand"
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in the Carer Burden Scale for Domain "Cutting the Fingernails of the Affected Hand"
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 4 in the Carer Burden Scale for Domain "Cleaning the Armpit of the Affected Arm"
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 12 in the Carer Burden Scale for Domain "Cleaning the Armpit of the Affected Arm"
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in the Carer Burden Scale for Domain "Cleaning the Armpit of the Affected Arm"
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 4 in the Carer Burden Scale for Domain "Putting the Affected Arm Through the Sleeve (e.g., Coat, Shirt, Jacket)"
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 12 in the Carer Burden Scale for Domain "Putting the Affected Arm Through the Sleeve (e.g., Coat, Shirt, Jacket)"
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in the Carer Burden Scale for Domain "Putting the Affected Arm Through the Sleeve (e.g., Coat, Shirt, Jacket)"
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
measure: Change From Baseline to Week 4 in the Carer Burden Scale for Domain "Applying a Splint on the Affected Arm"
timeFrame: Baseline, Week 4
measure: Change From Baseline to Week 12 in the Carer Burden Scale for Domain "Applying a Splint on the Affected Arm"
timeFrame: Baseline, Week 12
measure: Change From Baseline to Final Visit in the Carer Burden Scale for Domain "Applying a Splint on the Affected Arm"
timeFrame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)
Other outcomes:
measure: Onset of Treatment Effect [Classified]
timeFrame: Period starting at baseline injection of the Main Period up to onset of treatment effect
Locations:
city: Czech Republic
country: Czech Republic
city: Hungary
country: Hungary
city: Poland
country: Poland
Study officials:
affiliation: Merz Pharmaceuticals GmbH
name: Merz Pharmaceuticals
role: STUDY_CHAIR
References: