Treatment of Spasticity in the upper limb in childre

Phase 1

• Conditions: pper Limb Spasticity.; MedDRA version: 17.0Level: PTClassification code 10028335Term: Muscle spasticitySystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 17.0Level: LLTClassification code 10048970Term: Arm spasticitySystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2012-000062-38-HU
• Lead Sponsor: Allergan Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-11-06
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 412

Inclusion Criteria

• Male or female, 2 to 16 years and 11 months of age (prior to 17th birthday) at the day 1 visit
• Minimum weight of 10 kg at the screening and day 1 visits
• Upper limb monoplegic, hemiplegic, or triplegic spasticity (spasticity confirmed by Hypertonia Assessment Tool [HAT]) with single-arm sparing (only 1 arm requiring botulinum toxin treatment for spasticity during the study) resulting from cerebral palsy, or post-stroke with the stroke onset prior to age 2 and at least 12 months prior to the day 1 visit
• Patient’s spasticity meets at least one of the conditions below in the study limb at the screening and day 1 visits:
o Elbow flexor tone of 2 or greater as measured by the MAS-B AND elbow flexor muscle contracture of no more than 30 degrees, and/or
o Wrist flexor tone of 2 or greater with finger flexor tone of 1+ or greater as measured by the MAS-B
AND at least neutral position for wrist with fingers at maximum extension
• Gross Motor Function Classification System Expanded and Revised (GMFCS-E&R) level I to IV at the screening visit
• Manual Ability Classification System (MACS) level I to IV at the screening visit
• Patients who are on anti-spastic 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 30 days prior to the day 1 visit
• Patients who are on anti-epileptic medications must be on a stable dose and regimen for at least 30 days prior to the day 1 visit
• Patients who are on an intrathecal baclofen pump must be on a continuous infusion at a stable dose and regimen (ie, not on bolus infusions) for at least 30 days prior to the day 1 visit
• Written informed consent has been obtained from parent/legally authorized representative
• Written minor assent has been obtained in accordance with local laws and institutional review board (IRB)/independent ethics committee (IEC) requirements
• Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health and Research Study Information for United States [US] sites and written Data Protection consent for European Union [EU] sites)
• Negative urine pregnancy test at the screening and day 1 visits (for females of childbearing potential, defined as females post menarche)
Are the trial subjects under 18? yes
Number of subjects for this age range: 412
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Any uncontrolled clinically significant medical condition other than the one under study
- Any medical condition that may put the patient at increased risk with exposure to Botulinum Toxin Type A Purified Neurotoxin Complex, including diagnosed muscular dystrophy (eg, Duchenne’s muscular dystrophy), myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, mitochondrial disease, or any other significant disease that might interfere with neuromuscular function
- Fixed contracture of the principal muscle group (elbow or wrist) for the study limb
- Uncontrolled epilepsy defined as more than 1 generalized seizure in any month within the 3 months prior to the day 1 visit or history of any of the following within 9 months prior to the day 1 visit:of prolonged seizures or repetitive seizure activity requiring administration of a rescue benzodiazepine (oral, rectal, etc) more than once a month, seizures lasting more than 10 minutes, status epilepticus, or epilepsy with autonomic involvement.
- Patients with presence or history of any of the following within 12 months prior to the day 1 visit that may indicate a vulnerable respiratory state per the investigator’s clinical judgment: aspiration pneumonia, recurrent lower respiratory tract infections, uncontrolled asthma, or compromised respiratory function.
- Patients with presence or history (within 12 months prior to the day 1 visit) of aspiration or a condition(s) that, in the investigator’s opinion, may put the patient at an increased risk for aspiration (eg, significant drooling, chronic dysphagia [difficulty swallowing] requiring changes in diet, or clinically significant gastroesophageal reflux disease)
- Patients previously exposed to botulinum toxin therapy of any serotype who have a history of allergy or sensitivity to the toxin or its components or other significant adverse experiences that, in the investigator’s opinion, may put the patient at an unacceptable risk
- Botulinum toxin therapy of any serotype for any condition within 6 months prior to the day 1 visit
- History of treatment with phenol or alcohol block in the study limb within 12 months prior to the day 1 visit or planned treatment with phenol or alcohol block in any limb(s) during the study
- History of or planned treatment during the study with selective dorsal rhizotomy or deep brain stimulation
- Patient has had constraint-induced movement therapy within 2 months prior to the day 1 visit
- History of surgical intervention of the study limb (except for tendon lengthening more than 12 months prior to the day 1 visit) or planned surgical intervention of any limb(s) during the study.
- Previous casting within 6 months prior to the day 1 visit or splinting with a dynamic splint (eg, Dynasplint® or UltraFlex®) within 3 months prior to the day 1 visit for spasticity of the study limb or the affected lower limb(s), or planned casting or splinting with a dynamic splint (eg, Dynasplint or UltraFlex) for spasticity of the study limb or affected lower limb(s) during the study
- Females who are pregnant, nursing, or planning a pregnancy during the study
- Females of childbearing potential (defined as females post menarche) not using reliable means of contraception (see Section 4.5.1.1 for acceptable contraceptive methods)
- Patients with a significant risk of suicide within the 12 months prior to screening, or since screening at the day 1 visit.

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 2 doses (3 U/kg and 6 U/kg) of BOTOX with standardized occupational therapy (OT) in pediatric patients with upper limb spasticity.;Secondary Objective: None;Primary end point(s): The primary efficacy endpoints will be the average grade change from baseline to weeks 4 and 6 in MAS-B of the principal muscle group. For US FDA only, the grade change from baseline in MAS-B of the principal muscle group and CGI by Physician are co-primary efficacy variables. Grade change from baseline in MAS-B of principal muscle group and CGI<br>by Physician will be analyzed as co-primary endpoints for the average of weeks 4 and 6.;Timepoint(s) of evaluation of this end point: Baseline, weeks 4 and 6.