BOTOX(RegisteredTM) Treatment in Pediatric Lower Limb Spasticity: Double-blind Study. Protocol: 191622-111
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, 12-week study evaluating 2 doses of BOTOX, 4 and 8 U/kg, and placebo with standardized PT for the treatment of spasticity involving the ankle plantar flexors in monoplegic and hemiplegic children. Patients who successfully complete this study without major protocol deviations (eg, noncompliance to protocol-required procedures) will be given the option of enrolling in the open-label extension Study 191622-112 if they meet eligibility criteria.
The maximum study duration per patient will be approximately 16 weeks (including up to 4 weeks in the screening period). Patients will complete 8 study visits as follows: screening (week -4 to week -2), initiation of standardized PT (week -2), randomization and treatment visit (day 1), and post-injection follow-up visits at weeks 2, 4, 6, 8, and 12.
There will be 1 treatment cycle in the study. Only 1 affected lower limb (referred to as the study limb) will be treated. Patients will be randomized in a 1:1:1 ratio to one of the following treatment groups: 4 U/kg (not to exceed 150 U) + PT, 8 U/kg (not to exceed 300 U) + PT, or placebo + PT.
The following are requirements for entry into the study:
1. Male or female, 2 to 16 years and 11 months of age (prior to 17th birthday) at the day 1 visit
2. Minimum weight of 10 kg at the screening and day 1 visits
3. Monoplegic or hemiplegic patients with cerebral palsy who have dynamic muscle contracture (spasticity confirmed by Hypertonia Assessment Tool [HAT]) of the ankle plantar flexors associated with true equinus foot deformity as described by Rodda and Graham, 2001 (see Figure 1 in exclusion criteria). Equinovarus or equinovalgus deformities are acceptable.
4. MAS-B score >= 2 for the ankle plantar flexors and minimum range of dorsiflexion of 0 degrees of the ankle with knee fully extended in the study limb at screening and day 1 visits
5. Patients for whom study treatment in the 3 ankle plantar flexors (namely gastrocnemius, soleus, and tibialis posterior) of the study leg is appropriate
6. Gross Motor Function Classification System x Expanded and Revised (GMFCS-E&R) level I to IV at the screening visit
7. Stable medical condition in the investigator[Single Quote]s opinion
8. Acceptable clinical laboratory results at the screening visit
9. 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
10. 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
11. Written informed consent has been obtained from parent/legally authorized representative
12. Written minor assent has been obtained in accordance with local laws and institutional review board (IRB)/independent ethics committee (IEC) requirements
13. 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 US sites and written Data Protection consent for European Union [EU] sites)
14. Negative urine pregnancy test at the screening and day 1 visits (for females of childbearing potential, defined as females post menarche)
15. Has family commitment to comply with protocol-required procedures including weekly standardized PT sessions throughout the study
16. Patients who are appropriate candidates for the protocol-specified study treatment doses per investigator[Single Quote]s clinical judgment