Study to compare the efficacy and safety of NT 201 (botulinum toxin) with placebo for the treatment of lower limb spasticity caused by stroke or traumatic brain injury.
- Conditions
- Diagnosis of lower limb spasticity with or without upper limb spasticity of the same body side caused by stroke or traumatic brain injuryMedDRA version: 21.1Level: LLTClassification code 10058977Term: Spastic paresisSystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-001639-35-SK
- Lead Sponsor
- Merz Pharmaceuticals GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
Main inclusion criteria
• Female or male subject = 18 years and = 85 years at screening
• Diagnosis of lower limb spasticity with or without upper limb spasticity of the same body side caused by stroke or traumatic brain injury
• Disabling ankle flexor spasticity presenting as pes equinus or pes equinovarus
• Modified Ashworth Scale-Bohannon [MAS] score of 2 or 3 points in the ankle plantar flexor of the target lower limb (supine position, knee extended)
• Minimum passive range of motion in ankle of the target lower limb (supine position, knee extended): 10°dorsiflexion and 20°plantarflexion
• At least 4 months since last botulinum neurotoxin [BoNT] injection for treatment of spasticity or any other condition
• For subjects receiving anticoagulation therapy, the investigator confirms and documents that the subject has an:
o Activated partial thromboplastin time [aPTT] = 80 seconds (subjects on dabigatran or other direct thrombin inhibitors) or
o International normalized ratio [INR] value of = 2.5 (subjects on coumarins or other anticoagulants monitored by INR)
Main eligibility criteria for re-injection
• According to the experience-based opinion of the investigator, the subject must have a clinical need for 400 U of NT 201 in the affected lower limb
• Body weight at least 50 kg
• Negative urine pregnancy test for women of childbearing potential
• For subjects receiving anticoagulation therapy, the investigator confirms and documents that the subject has an:
o aPTT = 80 seconds (subjects on dabigatran or other direct thrombin inhibitors) or
o INR value of = 2.5 (subjects on coumarins or other anticoagulants monitored by INR)
• No infection or inflammation in the area of the planned injection sites at the visits
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 430
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 170
Main exclusion criteria
• Generalized disorders of muscle activity (e.g. myasthenia gravis, Lambert Eaton syndrome, amyotrophic lateral sclerosis) or any other significant peripheral neuromuscular dysfunction which might interfere with the study
• Bilateral lower limb paresis/paralysis/spasticity or tetraparesis/paralysis/spasticity
• Body weight < 50 kg
• Severe atrophy of the target limb muscles
• Previous, ongoing or planned treatments of spasticity with intrathecal baclofen
• Previous, ongoing, or planned treatments of spasticity in the target lower limb with any of the following procedures:
o Surgical intervention
o Alcohol or phenol block
o Muscle afferent block
• Physiotherapy or use of orthoses or splints at the target limb initiated less than 4 weeks before screening or expected to change during the double blind phase of the study
• Current or planned treatment with parenterally administered drugs that interfere with neuromuscular transmission (e.g. intrathecal baclofen, tubocurarine type muscle relaxants used in anesthesia),, or local anesthetics in the treated region within 2 weeks prior to screening
• Infection or inflammation at the injection sites
• Subjects with presence or history of aspiration pneumonia, recurrent lower respiratory tract infections, or compromised respiratory function as per investigator's clinical judgment
• Pregnancy (as verified by a positive pregnancy test) or breast feeding
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluation of the efficacy and safety of 400 U of NT 201 in the treatment of adult lower limb spasticity involving the ankle plantar flexors.;Secondary Objective: Evaluation of the long-term safety of NT 201 in the treatment of spasticity with total body doses up to 800 U.;Primary end point(s): Co-primary efficacy variables:<br>• Change from baseline in derived Modified Ashworth Scale-Bohannon<br>(MAS) ankle score (knee extended) at<br>Weeks 4 to 6 <br>Primary safety variable:<br>Occurrence of treatment emergent adverse events [TEAEs] in Main Period;Timepoint(s) of evaluation of this end point: Timepoints of evaluation of Co-primary efficacy variables:<br>• Modified Ashworth Scale-Bohannon (MAS) ankle score at baseline to Weeks 4 to 6 <br>Timepoint of evaluation of the primary safety variable:<br>•Baseline to week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Key secondary efficacy variable: <br>• Change from Study Baseline in Goal Attainment Scale [GAS] at week 6<br><br>Other secondary efficacy variables: <br>• Global Impression of Change Scale (GICS) assessed by physician at Week 4 to 6<br><br>• Global Impression of Change Scale (GICS) assessed by subject at week 4 to 6<br>• Global Impression of Change Scale (GICS) assessed by caregiver at week 4 to 6;Timepoint(s) of evaluation of this end point: • Goal Attainment Scale [GAS] at Week 4 to 6 <br><br>• GICS assessed by physician at Week 4 to 6<br>• GICS assessed by subject at Week 4 to 6<br>• GICS assessed by caregiver at Week 4 to 6