Lower Limb or Combined Lower Limb and Upper Limb Spasticity Due to Stroke or Traumatic Brain Injury
Conditions
Brief summary
The purpose of this study is to determine whether a single treatment with administration of 400 Units NT 201 (botulinum toxin) is superior to placebo (no medicine) for the treatment of lower limb spasticity caused by stroke or traumatic brain injury (Main Period). Participants will be assigned to the treatment groups by chance and neither the participants nor the research staff who interact with them will know the allocation. The following 4 to 5 treatment cycles will investigate the safety and tolerability of treatment with NT 201 (botulinum toxin) when administered in doses between 400 and 800 Units (Open Label Extension Period). All participants will receive the treatment and the dose will depend on whether only lower limb spasticity or combined upper and lower limb spasticity are treated.
Interventions
DRUGNT 201
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
DRUGPlacebo
Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
Sponsors
Merz Pharmaceuticals GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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: * Activated partial thromboplastin time \[aPTT\] ≤ 80 seconds (subjects on dabigatran or other direct thrombin inhibitors) or * International normalized ratio \[INR\] value of ≤ 2.5 (subjects on coumarins or other anticoagulants monitored by INR)
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: Surgical Intervention; Alcohol or phenol block; 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in derived Modified Ashworth Scale-Bohannon (MAS) ankle score (knee extended) at weeks 4 to 6 | Baseline to week 4-6 | The MAS is a 6-grade scale |
| Co-Primary: Global Impression of Change Scale (GICS) assessed by physician at Week 4 to 6 | Week 4-6 | The GICS s a 9-grade scale |
| Occurrence of treatment emergent adverse events [TEAEs] in the Main Period | Baseline to week 12 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Study Baseline in Goal Attainment Scale [GAS] at Week 6 | Baseline to week 6 | The GAS is a 6-grade scale |
| Global Impression of Change Scale (GICS) assessed by the study subject at Week 4 to 6 | Week 4-6 | The GICS s a 9-grade scale |
| Global Impression of Change Scale (GICS) assessed by the caregiver at Week 4 to 6 | Week 4-6 | The GICS s a 9-grade scale |
Countries
Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Poland, Russia, Slovakia, Spain, Switzerland, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORMerz Medical Expert
Merz Pharmaceuticals GmbH
Outcome results
None listed