Prospective, Randomized, Observer-blind, Parallel-group, Multi-center Trial to Assess Efficacy and Safety of Two Different Dilutions of incobotulinumtoxinA (Xeomin) in Patients With Upper Limb Spasticity
Overview
- Phase
- Phase 3
- Intervention
- incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kD), free from complexing proteins")
- Conditions
- Upper Limb Spasticity
- Sponsor
- Merz Pharmaceuticals GmbH
- Enrollment
- 216
- Primary Endpoint
- Responder in Disability Assessment Scale (DAS) at Week 4 - Per Protocol Set
- Status
- Completed
- Last Updated
- 15 years ago
Overview
Brief Summary
This study will investigate the efficacy and safety of incobotulinumtoxinA (Xeomin) in the treatment of arm tightness (upper limb spasticity) using two different dilutions of incobotulinumtoxinA (Xeomin).
Detailed Description
IncobotulinumtoxinA (Xeomin) is a botulinum toxin type A preparation free of complexing proteins. Injected into a muscle, incobotulinumtoxinA causes a reversible local weakening of the muscle for several months, and may improve an impaired muscle function by lessening the muscle tightness within few days. IncobotulinumtoxinA is widely used for various severe neurological conditions. There is some evidence that the treatment effect may be influenced by the amount of the solvent in which incobotulinumtoxinA is diluted before injection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female or male patients ≥ 18 years
- •Stable upper limb spasticity of diverse etiology
- •Focal spasticity with equal or more than 2 points on the Ashworth scale in the wrist flexors
- •Disability Assessment Scale (DAS) ≥ 2 points for primary therapeutic target at both screening and baseline visits
Exclusion Criteria
- •Fixed contracture
- •Bilateral upper limb paresis/paralysis
- •Previous treatment with BoNT of any serotype and for any body region within the 4 months prior to screening
- •Previous or planned treatment with phenol- or alcohol-injection in the target limb
- •Other muscle hypertonia (e.g. rigidity)
- •Diagnosis of myasthenia gravis, Lambert-Eaton-Syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease which might interfere with the study
- •Severe atrophy of the target limb muscles
Arms & Interventions
incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL
incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kD), free from complexing proteins")(active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection; Mode of administration: intramuscular injection; The content of the vial was dissolved in 5.0 mL of sterile sodium chloride \[NaCl\] 0.9% solution without preservatives. Dilution with 5.0 mL resulted in a dose of 20 units per 1.0 mL.
Intervention: incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kD), free from complexing proteins")
incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL
incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kD), free from complexing proteins")(active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection; Mode of administration: intramuscular injection; The content of the vial was dissolved in 2.0 mL sterile of NaCl 0.9% solution without preservatives. Dilution with 2.0 mL resulted in a dose of 50 units per 1.0 mL.
Intervention: incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kD), free from complexing proteins")
Outcomes
Primary Outcomes
Responder in Disability Assessment Scale (DAS) at Week 4 - Per Protocol Set
Time Frame: At week 4
The primary efficacy endpoint is the number of responder at Week 4; response defined as an improvement (reduction) of at least one point in the DAS for the primary therapeutic target from baseline visit to Week 4. The DAS determines the functional impairment for the domains hygiene, dressing, limb position and pain according to the following scale: 0 = no disability; 1 = mild disability; 2 = moderate disability; 3 = severe disability. At Screening visit, the subject and investigator, selected together one of the four domains as the primary therapeutic target.
Secondary Outcomes
- Responder in DAS at Week 4 - Full Analysis Set(week 4)
- Responder in DAS at Week 12 - Full Analysis Set(week 12)
- Responder in DAS at Follow up - Full Analysis Set(follow up visit, between week 12 and week 20)
- Responder in Frenchay Arm Test (FAT) at Week 4 - Full Analysis Set(Week 4)
- Responder in FAT at Week 12 - Full Analysis Set(Week 12)
- Responder in FAT at Follow up - Full Analysis Set(follow up visit, between week 12 and week 20)
- Responder in Ashworth Scale (Elbow Flexors) at Week 4 - Full Analysis Set(week 4)
- Responder in Ashworth Scale (Elbow Flexors) at Week 12 - Full Analysis Set(week 12)
- Responder in Ashworth Scale (Elbow Flexors) at Follow up - Full Analysis Set(follow up visit, between week 12 and week 20)
- Responder in Ashworth Scale (Wrist Flexors) at Week 4 - Full Analysis Set(week 4)
- Responder in Ashworth Scale (Wrist Flexors) at Week 12 - Full Analysis Set(week 12)
- Responder in Ashworth Scale (Wrist Flexors) at Follow up - Full Analysis Set(follow up visit, between week 12 and week 20)
- Responder in Ashworth Scale (Thumb Flexors) at Week 4 - Full Analysis Set(week 4)
- Responder in Ashworth Scale (Thumb Flexors) at Week 12 - Full Analysis Set(week 12)
- Responder in Ashworth Scale (Thumb Flexors) at Follow up - Full Analysis Set(follow up visit, between week 12 and week 20)
- Responder in Ashworth Scale (Fingers Flexors) at Week 4 - Full Analysis Set(week 4)
- Responder in Ashworth Scale (Fingers Flexors) at Week 12 - Full Analysis Set(week 12)
- Responder in Ashworth Scale (Fingers Flexors) at Follow up - Full Analysis Set(follow up visit, between week 12 and week 20)
- Responder in Ashworth Scale (Forearm Pronators) at Week 4 - Full Analysis Set(week 4)
- Responder in Ashworth Scale (Forearm Pronators) at Week 12 - Full Analysis Set(week 12)
- Responder in Ashworth Scale (Forearm Pronators) at Follow up - Full Analysis Set(follow up visit, between week 12 and week 20)
- Change From Baseline in Passive Range of Motion (PROM) - Wrist Extension(baseline, week 4, week 12, follow up (between week 12 and week 20))
- Change From Baseline in Passive Range of Motion (PROM) - Elbow Extension(baseline, week 4, week 12, follow up (between week 12 and week 20))
- Change From Baseline in Passive Range of Motion (PROM) - Wrist Maximum Flexion(baseline, week 4, week 12, follow up (between week 12 and week 20))
- Change From Baseline in Passive Range of Motion (PROM) - Elbow Maximum Flexion(baseline, week 4, week 12, follow up (between week 12 and week 20))
- Investigator's Global Assessment of Treatment Response (GATR) - Full Analysis Set(week 4)
- Patient's Global Assessment of Treatment Response (GATR) - Full Analysis Set(week 4)
- Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Feeding(week 4)
- Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Feeding(week 12)
- Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Feeding(follow up visit, between week 12 and week 20)
- Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Grooming(week 4)
- Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Grooming(week 12)
- Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Grooming(follow up visit, between week 12 and week 20)
- Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Toilet Use(week 4)
- Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Toilet Use(week 12)
- Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Toilet Use(follow up visit, between week 12 and week 20)
- Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Bathing/Showering(week 4)
- Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Bathing/Showering(week 12)
- Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Bathing/Showering(follow up visit, between week 12 and week 20)
- Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Dressing(week 4)
- Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Dressing(week 12)
- Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Dressing(follow up visit, between week 12 and week 20)