Clinical trial NCT01603459: Efficacy and Safety Dose Titration Study of Botulinum Toxin Type A to Treat Spasticity in the Leg and Arm
Official title: Prospective, Open-label, Non-randomized, Single-arm, Multi-center Dose Titration Study to Investigate the Safety and Efficacy of NT 201 in Subjects Deemed to Require Total Body Doses of 800 U of NT 201 During the Course of the Study for the Treatment of Upper and Lower Limb Spasticity of the Same Body Side Due to Cerebral Causes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spasticity of the Upper and Lower Limb Due to Cerebral Causes
Lead sponsor: Merz Pharmaceuticals GmbH
Sponsor class: INDUSTRY
First posted: 2012-05-22
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether injections with increasing doses (up to 800 units) of Botulinum toxin type A into muscles of the leg and/or arm are safe and effective in treating patients with spasticity on one body side due to cerebral causes.

Detailed description: A dose-titration approach will be used over three injection cycles, with a flexible observation period after injections of 12-16 weeks and a total duration of up to 48 weeks. Cycle 1 and 2: upper and/or lower limb to be treated; Cycle 3: upper and lower limb to be treated.

Eligibility criteria: Inclusion Criteria:

* Upper and lower limb spasticity of the same body side due to cerebral causes
* Time since event leading to spasticity in the target body side greater than 12 weeks
* Need for 800 units Botulinum toxin type A

Exclusion Criteria:

* Body weight below 50kg
* Fixed contractures of the target joint
* Generalized disorders of muscle activity like Myasthenia gravis that preclude use of Botulinum toxin type A
* Infection at the injection site

Primary outcomes:
measure: Occurrence of Treatment-Emergent Adverse Events (AEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) by Injection Cycle, Overall and Related to the Administration of Study Medication
timeFrame: From baseline to week 36-48
measure: Investigator's Global Assessment of Tolerability in Subjects
timeFrame: Up to Week 48
Secondary outcomes:
measure: Ashworth Scale (AS) Scores of the Target Joint Selected at Study Baseline Visit
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of Ashworth Scale (AS) Score of the Target Joint Selected at Study Baseline Visit From Injection Cycle Baseline Visits to Respective Control Visits
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of Ashworth Scale (AS) Score of the Target Joint Selected at Study Baseline Visit From Study Baseline Visit to Control Visits of Injection Cycles
timeFrame: From Study Baseline to Week 4, 16-20 and 28-36
measure: Change of Ashworth Scale (AS) Score of the Target Joint Selected at Study Baseline Visit From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit
timeFrame: From Study Baseline to Week 12-16, 24-32 and 36-48
measure: Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Injection Cycle Baseline Visits to Respective Control Visits
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Control Visits of Injection Cycles
timeFrame: From Study Baseline to Week 4, 16-20 and 28-36
measure: Change of Ashworth Scale (AS) Score of Every Joint Affected by Clinical Patterns of Spasticity From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit
timeFrame: From Study Baseline to Week 12-16, 24-32 and 36-48
measure: Resistance to Passive Movement Scale (REPAS) Scores of Treated Side
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of Resistance to Passive Movement Scale (REPAS) Score of Treated Side From Injection Cycle Baseline Visits to Respective Control Visits
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of Resistance to Passive Movement Scale (REPAS) Score of Treated Side From Study Baseline Visit to Control Visits of Injection Cycles
timeFrame: From Study Baseline to Week 4, 16-20 and 28-36
measure: Change of Resistance to Passive Movement Scale (REPAS) Score of Treated Side From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit
timeFrame: From Study Baseline to Week 12-16, 24-32 and 36-48
measure: Functional Ambulation Classification (FAC) Scale Scores
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of Functional Ambulation Classification (FAC) Score From Injection Cycle Baseline Visits to Respective Control Visits
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of Functional Ambulation Classification (FAC) Score From Study Baseline Visit to Control Visits of Injection Cycles
timeFrame: From Study Baseline to Week 4, 16-20 and 28-36
measure: Change of Functional Ambulation Classification (FAC) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit
timeFrame: From Study Baseline to Week 12-16, 24-32 and 36-48
measure: Goal Attainment Scale (GAS) Scores for Upper and Lower Limb, Respectively
timeFrame: From Cycle Baseline Visit to Week 12-16, 24-32 and 36-48
measure: Disability Assessment Scale (DAS) Scores in a Selected Principal Therapeutic Target Domain Affecting the Upper Limb
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of Disability Assessment Scale (DAS) Score in a Selected Principal Therapeutic Target Domain Affecting the Upper Limb From Injection Cycle Baseline Visits to Respective Control Visits
timeFrame: Week 4 of Each Cycle
measure: Change of Disability Assessment Scale (DAS) Score in a Selected Principal Therapeutic Target Domain Affecting the Upper Limb From Study Baseline Visit to Control Visits of Injection Cycles
timeFrame: From Study Baseline to Week 4, 16-20 and 28-36
measure: Change of Disability Assessment Scale (DAS) Score in a Selected Principal Therapeutic Target Domain Affecting the Upper Limb From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit.
timeFrame: From Study Baseline to Week 12-16, 24-32 and 36-48
measure: Global Assessment of Efficacy Scores
timeFrame: Week 12-16, 24-32 and 36-48
measure: EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Visual Analogue Scale (VAS) of EuroQoL 5-Dimensions Questionnaire (EQ-5D) Scores
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change in Visual Analogue Scale of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Injection Cycle Baseline Visits to Respective Control Visits
timeFrame: From Cycle Baseline to Week 4 of Each Cycle
measure: Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles
timeFrame: From Study Baseline to Week 4, 16-20 and 28-36
measure: Change in Visual Analogue Scale of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Control Visits of Injection Cycles
timeFrame: From Study Baseline to Week 4, 16-20 and 28-36
measure: Change of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit
timeFrame: From Study Baseline to Week 12-16, 24-32 and 36-48
measure: Change in Visual Analogue Scale of EuroQoL 5-dimensions Questionnaire (EQ-5D) Score From Study Baseline Visit to Injection Cycle Baseline Visits and End of Cycle 3 Visit
timeFrame: From Study Baseline to Week 12-16, 24-32 and 36-48
Other outcomes:
Locations:
city: Doral
country: United States
facility: Merz Investigational Site # 001197
state: Florida
city: Indianapolis
country: United States
facility: Merz Investigational Site # 001235
state: Indiana
city: New York
country: United States
facility: Merz Investigational Site # 001191
state: New York
city: Charlotte
country: United States
facility: Merz Investigational Site #001238
state: North Carolina
city: Cleveland
country: United States
facility: Merz Investigational Site # 001232
state: Ohio
city: Milwaukee
country: United States
facility: Merz Investigational Site #001237
state: Wisconsin
city: Calgary, AB
country: Canada
facility: Merz Investigational Site # 001203
city: Edmonton, AB
country: Canada
facility: Merz Investigational site #001195
city: Garches
country: France
facility: Merz Investigational Site # 033018
city: Montpellier
country: France
facility: Merz Investigational Site #033049
city: Nimes
country: France
facility: Merz Investigational Site # 033050
city: Aachen
country: Germany
facility: Merz Investigational Site #049191
city: Bad Aibling
country: Germany
facility: Merz Investigational Site #049297
city: Beelitz-Heilstätten
country: Germany
facility: Merz Investigational Site #049022
city: Berlin
country: Germany
facility: Merz Investigational Site #049298
city: Gießen
country: Germany
facility: Merz Investigational Site # 049153
city: Göttingen
country: Germany
facility: Merz Investigational Site #049295
city: Nümbrecht
country: Germany
facility: Merz Investigational Site #049300
city: Tübingen
country: Germany
facility: Merz Investigational Site #049296
city: Lecco
country: Italy
facility: Merz Investigational Site # 039005
city: Milano
country: Italy
facility: Merz Investigational Site # 039010
city: Milano
country: Italy
facility: Merz Investigational Site # 039015
city: Novara
country: Italy
facility: Merz Investigational Site # 039017
city: Passignano sul Trasimeno
country: Italy
facility: Merz Investigational Site #039013
city: San Giovanni Rotondo
country: Italy
facility: Merz Investigational Site #039016
city: Verona
country: Italy
facility: Merz Investigational Site #039014
city: Bergen
country: Norway
facility: Merz Investigational Site #047001
city: Lisboa
country: Portugal
facility: Merz Investigational Site # 351001
city: Lisbon
country: Portugal
facility: Merz Investigational Site # 351003
city: Madrid
country: Spain
facility: Merz Investigational Site #034007
city: Malaga
country: Spain
facility: Merz Investigational Site #034025
city: Manresa
country: Spain
facility: Merz Investigational Site #034022
city: Santander
country: Spain
facility: Merz Investigational Site #034024
Study officials:
affiliation: Merz Pharmaceuticals
name: Medical Expert
role: STUDY_DIRECTOR
References:
citation: Wissel J, Bensmail D, Ferreira JJ, Molteni F, Satkunam L, Moraleda S, Rekand T, McGuire J, Scheschonka A, Flatau-Baque B, Simon O, Rochford ET, Dressler D, Simpson DM; TOWER study investigators. Safety and efficacy of incobotulinumtoxinA doses up to 800 U in limb spasticity: The TOWER study. Neurology. 2017 Apr 4;88(14):1321-1328. doi: 10.1212/WNL.0000000000003789. Epub 2017 Mar 10.
citation: Fheodoroff K, Scheschonka A, Wissel J. Goal analysis in patients with limb spasticity treated with incobotulinumtoxinA in the TOWER study. Disabil Rehabil. 2022 Apr;44(8):1367-1373. doi: 10.1080/09638288.2020.1804627. Epub 2020 Aug 17.
citation: Fheodoroff K, Rekand T, Medeiros L, Kossmehl P, Wissel J, Bensmail D, Scheschonka A, Flatau-Baque B, Simon O, Dressler D, Simpson DM. Quality of life in subjects with upper- and lower-limb spasticity treated with incobotulinumtoxinA. Health Qual Life Outcomes. 2020 Mar 4;18(1):51. doi: 10.1186/s12955-020-01304-4.