Efficacy and Safety Dose Titration Study of Botulinum Toxin Type A to Treat Spasticity in the Leg and Arm

NCT01603459 | Completed Phase 3 Results DMC

• 2 other identifiers: MRZ60201_3053_12010-020886-26
• Study Type: interventional
• Target: 155
• Locations: 8 countries
• Sites: 33

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.

Conditions

Spasticity of the Upper and Lower Limb Due to Cerebral Causes

Outcome Measures

Primary Outcomes (2)

• 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

  Treatment-emergent Adverse Events (TEASs) are events observed from the time point of first injection until 16 weeks after last injection. Values reported here refer to the number of subjects affected.

  From baseline to week 36-48

• Investigator's Global Assessment of Tolerability in Subjects

  A 4-point Likert scale was used with the ratings 1 = very good, 2 = good, 3 = moderate, and 4 = poor.

  Up to Week 48

Secondary Outcomes (30)

• Ashworth Scale (AS) Scores of the Target Joint Selected at Study Baseline Visit

  From Cycle Baseline to Week 4 of Each Cycle

• Change of Ashworth Scale (AS) Score of the Target Joint Selected at Study Baseline Visit From Injection Cycle Baseline Visits to Respective Control Visits

  From Cycle Baseline to Week 4 of Each Cycle

• 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

  From Study Baseline to Week 4, 16-20 and 28-36

• 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

  From Study Baseline to Week 12-16, 24-32 and 36-48

• Ashworth Scale (AS) Scores of Every Joint Affected by Clinical Patterns of Spasticity

  From Cycle Baseline to Week 4 of Each Cycle

Study Arms (1)

IncobotulinumtoxinA (Xeomin) (up to 800 Units)

EXPERIMENTAL

IncobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection

Drug: IncobotulinumtoxinA

Interventions

IncobotulinumtoxinA DRUG

Subjects to receive up to 3 injection cycle, with the dose titrated from 400 units to up to 800 units. For each injection session: solution prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 400-800 units, volume 2.0 mL per 100 units; Mode of administration: intramuscular injection.

IncobotulinumtoxinA (Xeomin) (up to 800 Units)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merz Pharmaceuticals GmbH: lead

Study Sites (33)

Merz Investigational Site # 001197

Doral, Florida, 33172, United States

Location

Merz Investigational Site # 001235

Indianapolis, Indiana, 46202, United States

Location

Merz Investigational Site # 001191

New York, New York, 10029, United States

Location

Merz Investigational Site #001238

Charlotte, North Carolina, 28203, United States

Location

Merz Investigational Site # 001232

Cleveland, Ohio, 44195, United States

Location

Merz Investigational Site #001237

Milwaukee, Wisconsin, 53226, United States

Location

Merz Investigational Site # 001203

Calgary, AB, T2N 2T9, Canada

Location

Merz Investigational site #001195

Edmonton, AB, T5G 0B7, Canada

Location

Merz Investigational Site # 033018

Garches, 92380, France

Location

Merz Investigational Site #033049

Montpellier, 34295, France

Location

Merz Investigational Site # 033050

Nîmes, 30029, France

Location

Merz Investigational Site #049191

Aachen, 52074, Germany

Location

Merz Investigational Site #049297

Bad Aibling, 83043, Germany

Location

Merz Investigational Site #049022

Beelitz-Heilstätten, 14547, Germany

Location

Merz Investigational Site #049298

Berlin, 10178, Germany

Location

Merz Investigational Site # 049153

Giessen, 35385, Germany

Location

Merz Investigational Site #049295

Göttingen, 37075, Germany

Location

Merz Investigational Site #049300

Nümbrecht, 51588, Germany

Location

Merz Investigational Site #049296

Tübingen, 72076, Germany

Location

Merz Investigational Site # 039005

Lecco, 23845, Italy

Location

Merz Investigational Site # 039010

Milan, 20122, Italy

Location

Merz Investigational Site # 039015

Milan, 20157, Italy

Location

Merz Investigational Site # 039017

Novara, 28100, Italy

Location

Merz Investigational Site #039013

Passignano sul Trasimeno, 06065, Italy

Location

Merz Investigational Site #039016

San Giovanni Rotondo, 71013, Italy

Location

Merz Investigational Site #039014

Verona, 37134, Italy

Location

Merz Investigational Site #047001

Bergen, 5053, Norway

Location

Merz Investigational Site # 351003

Lisbon, 1150-199, Portugal

Location

Merz Investigational Site # 351001

Lisbon, 1649-028, Portugal

Location

Merz Investigational Site #034007

Madrid, 28046, Spain

Location

Merz Investigational Site #034022

Manresa, 08242, Spain

Location

Merz Investigational Site #034025

Málaga, 29009, Spain

Location

Merz Investigational Site #034024

Santander, 39008, Spain

Location

Related Publications (3)

• 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.

  PMID: 28283596 RESULT

• 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.

  PMID: 32805151 DERIVED

• 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.

  PMID: 32131842 DERIVED

MeSH Terms

Interventions

incobotulinumtoxinA

Results Point of Contact

• Title: Public Disclosure Manager
• Organization: Merz Pharmaceuticals GmbH

clinicaltrials@merz.de

+49 69 1503 1

Study Officials

• Medical Expert

  Merz Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2012
• First Posted: May 22, 2012
• Study Start: May 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: April 26, 2017
• Results First Posted: February 3, 2017

Record last verified: 2017-03

Locations

IT (7); CA (2); FR (3); US (6); DE (8); NO (1); PT (2); ES (4)