Clinical trial NCT01205451: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spasticity, Post-Stroke
Keywords: GSK1358820
upper limb
spasticity
post-stroke
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-09-20
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

Detailed description: This trial is a multicenter, open-label study to evaluate the safety and efficacy of GSK1358820 for the treatment of patients with focal wrist, finger and in some cases, thumb spasticity post-stroke. Qualified patients will be eligible for enrollment upon completion of double-blind study 112958. Patients will receive a single treatment session with intramuscular injections of GSK1358820 "200U or 240U (if thumb spasticity is present)".The subjects will be observed for 12 weeks post injection.

Each completed subject will attend 4 clinic visits. The maximum study duration is 13 weeks. The study includes a 1 week pretreatment period, during which the screening visit (visit 1 could be the last visit of previous double-blind study 112958 or any time within 3 months after completion of previous study) is to take place. Only one upper limb (meeting inclusion/exclusion criteria) will be evaluated and treated in the study. Subjects will receive a single intramuscular treatment with investigated drug at day 0 (visit 2). There will be two post-injection follow-up visits at week 6 and 12 (visits 3 to 4).

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.

Primary outcomes:
measure: Change From Baseline at Week 6 and Week 12 for Wrist Flexor Muscle Tone as Measured on the Modified Ashworth Scale (MAS)
timeFrame: Baseline (Day 0), Week 6, and Week 12
Secondary outcomes:
measure: Number of Participants Classified as Wrist Treatment Responders at Week 6 and Week 12
timeFrame: Baseline (Day 0), Week 6, and Week 12
measure: Change From Baseline at Week 6 and Week 12 for Finger Flexor Muscle Tone as Measured on the MAS
timeFrame: Baseline (Day 0), Week 6, and Week 12
measure: Change From Baseline at Week 6 and Week 12 for Thumb Flexor Muscle Tone as Measured on the MAS
timeFrame: Baseline (Day 0), Week 6, and Week 12
measure: Change From Baseline at Week 6 and Week 12 for the Principal Measure as Assessed on the Disability Assessment Scale (DAS)
timeFrame: Baseline (Day 0), Week 6, and Week 12
measure: Global Assessment Scale (GAS) Score as Evaluated by the Physician at Week 6 and Week 12
timeFrame: Week 6 and Week 12
measure: GAS Score as Evaluated by the Care Giver or the Participant at Week 6 and Week 12
timeFrame: Week 6 and Week 12
measure: Mean Change From Baseline in Red Blood Cell (RBC) Count at the Exit Visit
timeFrame: Baseline (Day 0) and exit visit (Week 12 or earlier)
measure: Mean Change From Baseline in White Blood Cell (WBC) and Platelet Count at the Exit Visit
timeFrame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
measure: Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit
timeFrame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
measure: Mean Change From Baseline in Hemoglobin Content at the Exit Visit
timeFrame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
measure: Mean Change From Baseline in Hematocrit Value at the Exit Visit
timeFrame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
measure: Mean Change From Baseline in Total Protein and Albumin Values at the Exit Visit
timeFrame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
measure: Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit
timeFrame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
measure: Mean Change From Baseline in Serum Creatinine, Uric Acid, and Total Bilirubin Values at the Exit Visit
timeFrame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
measure: Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit
timeFrame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
measure: Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits
timeFrame: Screening visit (-Week 1) and the exit visit (Week 12 or earlier)
measure: Mean Change From Baseline in Systolic Blood Pressure (BP) and Diastolic BP at the Exit Visit
timeFrame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
measure: Mean Change From Baseline in Pulse Rate at the Exit Visit
timeFrame: Baseline (Screening) and the exit visit (Week 12 or earlier)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Haerbin
country: China
facility: GSK Investigational Site
state: Heilongjiang
city: Wuhan
country: China
facility: GSK Investigational Site
state: Hubei
city: Nanjing
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Suzhou
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Shenyang
country: China
facility: GSK Investigational Site
state: Liaoning
city: Chengdu
country: China
facility: GSK Investigational Site
state: Sichuan
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Hangzhou
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: