Study with BOTOX® for patients with post-stroke leg muscle tightness

Conditions: Post-Stroke Lower Limb Spasticity
MedDRA version: 16.1Level: LLTClassification code 10024132Term: Leg spasticitySystem Organ Class: 100000004852
MedDRA version: 16.1Level: LLTClassification code 10042244Term: StrokeSystem Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2011-004980-63-PL

Lead Sponsor: Allergan Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 418

Inclusion Criteria

1. male or female, =18 to = 85 years of age at the screening visit
2. patients who are diagnosed with post-stroke lower limb spasticity present with equinus (plantar flexion of the ankle) or equinovarus deformity, with the most recent stroke occurring at least 3 months prior to the screening visit
3. a minimum body weight of 50 kg at the screening visit
4. written informed consent has been obtained
5. written documentation has been obtained in accordance with the
relevant country and local privacy requirements, where applicable (e.g. Written Authorization for Use and Release of Health and Research Study Information (United States (US) sites) and written Data Protection consent (European Union (EU) sites).
6. MAS-B score of = 3 in the ankle plantar flexors at both screening and day 1 visits
7. botulinum toxin treatment-naïve or if previously treated with
botulinum toxin of any serotype:
- = 20 weeks prior to the day 1 visit if treated for spasticity of the study limb, or
- = 12 weeks prior to the day 1 visit if treated for an indication other than spasticity of the study limb
8. acceptable clinical laboratory results at screening at the investigator's discretion
9. for females of childbearing potential, a negative urine pregnancy test at screening and on the day 1 visit
10. patients who are on spasmolytic medications or muscle relaxants (eg, oral baclofen, tizanidine, dantrolene, scopolamine [oral or patch], vigabatrin, or benzodiazepine therapy) must be on a stable dose and regimen for at least 2 months prior to the day 1 visit
11. patients who are on anti-epileptic medications must be on a stable dose and regimen for at least 1 month prior to the day 1 visit
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 222
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 196

Exclusion Criteria

1. patients with spasticity in the contralateral leg that requires
treatment
2. presence of fixed contractures of the ankle (absence of range of
motion) in the study leg
3. profound atrophy of the muscles to be injected at the investigator's discretion
4. previous surgical intervention, phenol block, ethanol block, or muscle afferent block:
a) prior to screening for the treatment of spasticity in the study limb for muscles eligible for double-blind treatment, or
b) within 6 months prior to screening for any other muscles in the upper or lower limbs
5. casting of the study limb within 6 months prior to the screening visit and/or plans to cast the study limb during the double-blind phase of the study
6. treatment modalities in the study limb, including ultrasound therapy, transcutaneous electrical nerve stimulation, electrical stimulation, or acupuncture within 1 month of the day 1 visit or planned during the double-blind phase of the study
7. etiology other than stroke contributing to lower limb spasticity (eg, multiple sclerosis, traumatic brain injury, spinal cord injury)
8. infection of local skin, soft tissue, and joint in the areas to be injected or patients at a high risk of infection (eg, under immunosuppression treatments)
9. history of severe, progressive, or current unstable medical conditions as determined by medical history, physical examination and/or laboratory tests
10. patients with presence or history of aspiration pneumonia, recurrent lower respiratory tract infections, or compromised respiratory function per investigator's clinical judgment
11. patients with an active malignancy of any type or a history of
malignancy within the last 5 years (except basal cell carcinoma of the skin or squamous cell carcinoma of the skin with clean margins that has been excised at least 12 weeks prior to screening)
12. history of substance abuse or dependence within 12 months prior to the screening visit, excluding nicotine and caffeine
13. known allergy or sensitivity to the study medication(s) or its
components
14. nonambulatory patients defined as patients not able to perform the
10 meter walking test independently with or without assistive device
15. females who are pregnant, nursing, or planning a pregnancy during the study period
16. females of childbearing potential, not using a reliable means of
contraception [See protocol Section 4.5.1.1 for definition of acceptable methods of contraception]
17. current enrollment in an investigational drug, nonpharmacological treatment or interventional device study or participation in such a study within 30 days prior to the screening visit
18. any medical or neurological condition that may put the patient at increased risk with exposure to BOTOX, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant diseases or concomitant medications that might interfere with neuromuscular function
19. Patient has a condition, is planning a surgery requiring general
anesthesia during the study, or is in a situation which in the
investigator's opinion may put the patient at significant risk, may
confound the study results, or may interfere significantly with the
patient's participation in the study.
20. Patients on intrathecal baclofen pump
21. Physical therapy (physiotherapy) or use of static or dynamic splints including dynamic ankle foot orthosis (AFO), in the study limb that is initiated less than 14 days pri

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and efficacy of a single treatment of BOTOX (300 units (U) plus optional dose up to 100 U) in the treatment of adult post-stroke lower limb spasticity involving the ankle plantar flexors;Secondary Objective: NA;Primary end point(s): Primary efficacy measure is MAS-B score for the ankle plantor flexors ;Timepoint(s) of evaluation of this end point: Every clinic visit MAS-B will be performed by the investigator

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary measures:<br>• CGI by Physician<br>• MAS-B for optional muscles (flexor digitorum longus, flexor digitorum brevis, flexor hallucis longus, extensor hallucis, and rectus femoris) in a subset of patients who receive study treatment in the optional muscles<br>• Goal Attainment Scaling (GAS) by Physician and Patient<br>• Pain Scale (11-point numeric rating scale)<br>;Timepoint(s) of evaluation of this end point: Assessments are done during the study visits: CGI - visits at week 2, 4, 6, 8, 12, open label treatments day 1 visits and week 6 visits, exit visit;<br>MAS-B for optional muscles - at every clinic visit; <br>GAS - visits at week 8, 12, open label treatments day 1 and week 6 visits, exit visit; <br>Pain Scale - visits at day 1, week 2, 4, 6, 8, 12, open label treatments day 1 and week 6, exit visit