A Multicenter, Open-label, Single Dose Study of the Safety and Efficacy of GSK1358820 (Botulinum Toxin Type A) in Chinese Subjects With Post-stroke Focal Upper Limb Spasticity
Condition: Spasticity, Post-Stroke
MeSH terms: Muscle Spasticity; Stroke
Intervention: Botulinum toxin type A
Intervention description: Botulinum toxin type A
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 109.0
Sex: All
Minimum age: 18 Years
Maximum age: 76 Years
Healthy volunteers: No
Keywords: GSK1358820; upper limb; spasticity; post-stroke

Summary:

      This trial is a multicenter, open-label study to evaluate the safety and efficacy of
      GSK1358820 for treatment in post-stroke subjects with focal wrist, finger and in some cases,
      thumb spasticity. Qualified patients who complete GSK double-blind study 112958 will be
      enrolled. Subjects will receive a single treatment session of intramuscular GSK1358820 "200U
      or 240U (if thumb spasticity is present)". 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. Safety parameters will be measured including adverse events, vital signs
      (pulse and blood pressure) and clinical laboratory tests (haematology, serum chemistry and
      urinanalysis).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Within 3 months after completion of the GSK/Allergan study 112958.

          2. Wrist flexor muscle tone of 2 or greater and finger flexor muscle tone of 1 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 physical therapy, must be stable for at least 1 month prior to study
             enrolment in study 112958.

          5. >=40kg in weight.

          6. 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.

          7. 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%).

          8. 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.

          9. Informed consent has been obtained

        Exclusion Criteria:

          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 (with the exception of study 112958) , within
             the 30 days immediately prior to enrolment.

          9. Planned or anticipated initiation of new antispasticity medications during the
             clinical study.

         10. 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.

         11. 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.

         12. Current treatment for spasticity with an intrathecal baclofen.

         13. 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.

         14. Known allergy or sensitivity to study medication or its components.

         15. Bedridden subjects.

         16. 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).

         17. Presence of clinically unstable severe cardiovascular, renal or respiratory disease.

         18. 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.