A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Chinese Subjects With Post-stroke Upper Limb Spasticity
Condition: Cerebrovascular Accident
MeSH terms: Muscle Spasticity; Stroke
Intervention: GSK1358820(Botulinum toxin type A); placebo
Intervention description: GSK1358820 (Botulinum Toxin Type A, also known as "OnabotulinumtoxinA" or "Botox"); placebo
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 170.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: efficacy; Spasticity, Post-Stroke; safety; Botulinum toxin type A; placebo; spasticity

Summary:

      This trial is a multicenter, double-blind, randomized, placebo-controlled study to compare
      GSK1358820 (Botulinum Toxin Type A, also known as "OnabotulinumtoxinA" or "Botox") with
      placebo on the efficacy and safety of treatment in poststroke subjects with focal wrist,
      finger and in some cases, thumb spasticity. Approximately 168 subjects will be enrolled.
      Subjects will receive a single treatment session of intramuscular GSK1358820 (Botulinum Toxin
      Type A, also known as "OnabotulinumtoxinA" or "Botox") '200U or 240U (if thumb spasticity is
      present)' or placebo in a randomization ratio of 1:1. The subjects will be observed until 12
      weeks post injection. Outcome measures include changes from baseline at every post injection
      visit as measured on the Modified Ashworth Scale (MAS), Disability Assessment Scale (DAS) and
      Global Assessment Scale. The primary efficacy endpoint is the change from baseline at week 6
      for wrist flexor muscle tone as measured on the Modified Ashworth Scale. Safety parameters
      will also be measured including adverse events, vital signs (pulse and blood pressure) and
      clinical laboratory tests (haematology, serum chemistry and urinanalysis).
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects eligible for enrolment in the study must meet all of the following criteria:

          1. Subjects with upper limb spasticity who are at least 6 months post stroke and present
             with spasticity of both the wrist and fingers in the study limb.

          2. Wrist flexor muscle tone of 3 or greater and finger flexor muscle tone of 2 or greater
             as measured on MAS (0 to 4).

          3. At least one functional disability item (i.e., hygiene, dressing, pain, or cosmesis)
             with a rating of 2 or greater on DAS (0 to 3).

          4. If using oral anti-spasticity medications, must be stable for at least 1 month prior
             to study enrolment

          5. If using physical therapy, must be stable for at least 1 month prior to study
             enrolment.

          6. Male or female 18 to 75 years old at the time of informed consent.

          7. >=40kg in weight.

          8. QTc criteria: (either QTcb or QTcf, machine or manual overread, males or females);
             include the following details as appropriate: QTc<450 millisecond (msec) or <480msec
             for subjects with Bundle Branch Block-values based on either single electrocardiogram
             (ECG) values or triplicate ECG averaged QTc values obtained over a brief recording
             period.

          9. Liver function tests: aspartate aminotransferase (AST) and alanine aminotransferase
             (ALT) <2xULN; alkaline phosphatase and bilirubin ≤1.5xULN (isolated bilirubin >1.5ULN
             is acceptable if bilirubin is fractionated and direct bilirubin <35%).

         10. In the opinion of the investigator, subject must clearly understand the intent of the
             study and be willing and able to comply with study instructions and complete the
             entire study.

         11. Informed consent has been obtained.

        Exclusion Criteria:

        Subjects meeting any of the following criteria must not be enrolled in the study:

          1. Presence of fixed contracture of the study limb (absence of passive range of motion).

          2. Profound atrophy of muscles to be injected (in the investigators opinion).

          3. Infection or dermatological condition at the injection sites.

          4. Significant inflammation in the study limb limiting joint movement.

          5. History of or planned treatment for spasticity with phenol or alcohol block in the
             study limb.

          6. History of or planned surgical intervention for spasticity of the study limb.

          7. History (within 3 months of qualification) of or planned (during study period) casting
             of the study limb.

          8. Participation in another clinical study currently, or within the 30 days immediately
             prior to enrolment.

          9. Previous or current botulinum toxin therapy of any serotype.

         10. Planned or anticipated initiation of new antispasticity medications during the
             clinical study.

         11. Any medical condition that may put the subject at increased risk with exposure to
             GSK1358820, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic
             lateral sclerosis, or any other disorder that might have interfered with neuromuscular
             function.

         12. Concurrent use of aminoglycoside antibiotics or other agents that might interfere with
             neuromuscular function. A full list of prohibited medications that interfere with
             neuromuscular transmission is provided as Appendix 1.

         13. Current treatment for spasticity with an intrathecal baclofen.

         14. Females who are pregnant, nursing, or planning a pregnancy during the study period, or
             females of childbearing potential, not using a reliable means of contraception.

         15. Known allergy or sensitivity to study medication or its components.

         16. Bedridden subjects.

         17. Unstable liver disease (as defined by the presence of ascites, encephalopathy,
             coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice),
             cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or
             asymptomatic gallstones).

         18. Presence of clinically unstable severe cardiovascular, renal or respiratory disease.

         19. Investigator's opinion that the subject has a concurrent condition(s) that may put the
             subject at significant risk, may confound the study results, or may interfere
             significantly with the conduct of the study.