IncobotulinumtoxinA (Xeomin) for Upper Limb Spasticity

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

Sponsors

Lead Sponsor: Merz Pharmaceuticals GmbH

Source Merz Pharmaceuticals GmbH
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.

Overall Status Completed
Start Date February 2007
Completion Date May 2008
Primary Completion Date January 2008
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Responder in Disability Assessment Scale (DAS) at Week 4 - Per Protocol Set At week 4
Secondary Outcome
Measure Time Frame
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
Enrollment 216
Condition
Intervention

Intervention Type: Drug

Intervention Name: incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kD), free from complexing proteins")

Description: 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 or 5.0 mL of sterile sodium chloride [NaCl] 0.9% solution without preservatives. Dilution with 2.0 or 5.0 mL resulted in a dose of 50 or 20 units per 1.0 mL.

Eligibility

Criteria:

Main 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

Main 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Michael P Barnes, MD, FRCP Principal Investigator Hunters Moor Hospital, Newcastle-upon-Tyne, UK
Location
Facility:
| Hermagor, Austria
| Innsbruck, Austria
| Vienna, Austria
| Besancon, France
| Garches, France
| Lille, France
| Paris, France
| Beelitz-Heilstaetten, Germany
| Duesseldorf, Germany
| Gladbeck, Germany
| Bari, Italy
| Costa Masnaga, Italy
| Messina, Italy
| Mestre, Italy
| Milano, Italy
| Rome, Italy
| Lisbon, Portugal
| Tocha, Portugal
| Barcelona, Spain
| Madrid, Spain
| Terrassa, Spain
| Bern, Switzerland
| Nottwil, Switzerland
| Kent, United Kingdom
| Liverpool, United Kingdom
| Plymouth, United Kingdom
| Wakefield, United Kingdom
Location Countries

Austria

France

Germany

Italy

Portugal

Spain

Switzerland

United Kingdom

Verification Date

December 2010

Responsible Party

Name Title: Central Medical Affairs

Organization: Merz Pharmaceuticals GmbH

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL

Type: Experimental

Description: 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.

Label: incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL

Type: Active Comparator

Description: 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.

Acronym NT-Spin
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Single (Outcomes Assessor)

Source: ClinicalTrials.gov