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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier:
NCT01603459
First received: April 17, 2012
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Spasticity of the Upper and Lower Limb Due to Cerebral Causes
Drug: IncobotulinumtoxinA
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merz Pharmaceuticals GmbH:

Primary Outcome Measures:
  • Occurence of treatment-emergent Adverse Events (AEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) by injection cycle [ Time Frame: Week 12-16 ] [ Designated as safety issue: Yes ]
  • Occurence of treatment-emergent AEs, AESIs, and SAEs related to the administration of study medication by injection cycle [ Time Frame: Week 12-16 ] [ Designated as safety issue: Yes ]
  • Investigator's global assessment of tolerability using a 4-point Likert scale at end of injection cycle visits [ Time Frame: Week 12-16 ] [ Designated as safety issue: Yes ]
    A 4-point Likert scale will be used with the ratings 1 = very good, 2 = good, 3 = moderate, and 4 = poor.

  • Occurence of treatment-emergent Adverse Events (AEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) by injection cycle [ Time Frame: Week 24-32 ] [ Designated as safety issue: Yes ]
  • Occurence of treatment-emergent Adverse Events (AEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) by injection cycle [ Time Frame: Week 36-48 ] [ Designated as safety issue: Yes ]
  • Occurence of treatment-emergent AEs, AESIs, and SAEs related to the administration of study medication by injection cycle [ Time Frame: Week 24-32 ] [ Designated as safety issue: Yes ]
  • Occurence of treatment-emergent AEs, AESIs, and SAEs related to the administration of study medication by injection cycle [ Time Frame: Week 36-48 ] [ Designated as safety issue: Yes ]
  • Investigator's global assessment of tolerability using a 4-point Likert scale at end of injection cycle visits [ Time Frame: Week 24-32 ] [ Designated as safety issue: Yes ]
    A 4-point Likert scale will be used with the ratings 1 = very good, 2 = good, 3 = moderate, and 4 = poor.

  • Investigator's global assessment of tolerability using a 4-point Likert scale at end of injection cycle visits [ Time Frame: Week 36-48 ] [ Designated as safety issue: Yes ]
    A 4-point Likert scale will be used with the ratings 1 = very good, 2 = good, 3 = moderate, and 4 = poor.


Secondary Outcome Measures:
  • Ashworth Scale (AS) of the target joint selected at study baseline visit [ Time Frame: From baseline up to week 48 ] [ Designated as safety issue: No ]
    The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

  • AS of every joint affected by clinical patterns of spasticity and treated at least once, of the same body side as the selected target joint. [ Time Frame: From baseline up to week 48 ] [ Designated as safety issue: No ]
    The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

  • Resistance to passive movement scale (REPAS) [ Time Frame: From baseline up to week 48 ] [ Designated as safety issue: No ]
    The REPAS is a summary 26-item test used to assess resistance to passive movement in all four limbs of the body. It provides a global evaluation of spasticity status, as well as per hemibody and per limb. 16 items describe the condition of both upper limbs, 10 that of both lower limbs. Each item is rated by using the Ashworth Scale. The sum of the values represent the REPAS score which may range from zero (no resistance for any item) to 104 (limbs rigid for all items).

  • Functional ambulation classification (FAC) scale [ Time Frame: From baseline up to week 48 ] [ Designated as safety issue: No ]

    The FAC examines the independence and ambulation of subjects whereby supervision/physical assistance from 1 person is allowed. Subjects are classified to following categories:

    Level 0: no functional ambulation; Level 1: Ambulator-dependent for physical assistance (Level II); Level 2: Ambulator-dependent for physical assistance (Level I); Level 3: Ambulator-dependent for supervision; Level 4: Ambulator-independent, level surface only; Level 5: Ambulator-independent.


  • Global attainment scale (GAS) for upper and lower limb, respectively [ Time Frame: Up to week 48 ] [ Designated as safety issue: No ]
    GAS measures the extent to which a subject's individual goals are achieved in the course of intervention. Subject and treating team have to identify 2 personal goals for each treated limb at each injection cycle. Investigator rates the GAS score for each injection cycle. Each goal is rated on a 5-point scale, with degree of attainment captured for each goal area: -2 = a lot less than expected; -1 = a little less than expected; 0 = expected level of achievement; +1 = a little better than expected; +2 = a lot better than expected. The GAS score at injection cycle baseline is always set as -1.

  • Disability Assessment Scale (DAS) in a selected principal therapeutic target domain affecting the upper limb [ Time Frame: From baseline up to week 48 ] [ Designated as safety issue: No ]
    The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which are assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). One of the domains will be selected per injection cycle.

  • EuroQoL 5-dimensions questionnaire (EQ-5D) [ Time Frame: From baseline up to week 48 ] [ Designated as safety issue: No ]
    The EQ-5D is a common quality of life questionnaire to be filled out by the subject.

  • Global assessment of efficacy [ Time Frame: Up to week 48 ] [ Designated as safety issue: No ]
    The global assessment of efficacy will be assessed by the investigator, the subject, and the caregiver using a 4-point Likert scale with the ratings 1 = very good, 2 = good, 3 = moderate, and 4 = poor.


Enrollment: 150
Study Start Date: May 2012
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IncobotulinumtoxinA (Xeomin) (up to 800 Units)
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

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.


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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01603459

  Show 33 Study Locations
Sponsors and Collaborators
Merz Pharmaceuticals GmbH
Investigators
Study Director: Medical Expert MERZ Pharmaceuticals
  More Information

No publications provided

Responsible Party: Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier: NCT01603459     History of Changes
Other Study ID Numbers: MRZ60201_3053_1, 2010-020886-26
Study First Received: April 17, 2012
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Italy: The Italian Medicines Agency
Canada: Health Canada
Norway: Norwegian Medicines Agency
Portugal: INFARMED, National Authority of Medicines and Health Products, IP

Additional relevant MeSH terms:
Muscle Spasticity
Muscle Hypertonia
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Manifestations
Signs and Symptoms
Botulinum Toxins
Botulinum Toxins, Type A
Anti-Dyskinesia Agents
Central Nervous System Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014