Phase 3
N=124
A Phase III Study to Evaluate the Efficacy and Safety of GSK1358820 in Subjects With Post-stroke Upper Limb Spasticity
Spasticity, Post-Stroke
Bottom Line
View on ClinicalTrials.gov: NCT03261167 ↗Enrolled (actual)
124
Serious AEs
3.9%
Results posted
Oct 2019
Primary outcome: Primary: Percentage of Participants Who Had Modified Ashworth Scale (MAS) Score Reduced at Least 1 From Baseline in the Elbow Flexors at Week 6 — 50.8; 68.9 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Botulinum toxin A (GSK1358820) (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 20+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Mar 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Had Modified Ashworth Scale (MAS) Score Reduced at Least 1 From Baseline in the Elbow Flexors at Week 6 |
50.8; 68.9 | — |
| SECONDARY Percentage of Participants Who Had MAS Score Reduction in Elbow, Wrist, Finger and Thumb Flexors up to Week 12 |
44.4; 77.0; 52.4; 73.8; 50.8; 68.9 | — |
| SECONDARY Change From Baseline in MAS Scores in Elbow, Wrist, Finger and Thumb Flexors up to Week 12 (Mixed Model Repeated Measures [MMRM]) |
-0.59; -1.07; -0.7; -1.12; -0.71; -1.09 | — |
| SECONDARY Change From Baseline in Principal Therapeutic Target of Disability Assessment Scale (DAS) - MMRM up to Week 12 |
-0.34; -0.59; -0.46; -0.62; -0.52; -0.67 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) After 84 Days of First Treatment |
29; 31; 4; 5 | — |
| SECONDARY Number of Participants With AEs and SAEs-Overall Study Period |
52; 49; 6; 8 | — |
| SECONDARY Number of Participants With Abnormal Findings After Physical Examinations |
— | — |
| SECONDARY Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline |
7; 3; 5; 5; 1; 5 | — |
| SECONDARY Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline |
5; 6; 8; 6; 3; 2 | — |
| SECONDARY Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Analysis |
11; 11; 4; 2; 2; 7 | — |
| SECONDARY Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 and Week 48 |
0.8; 1.3; 0.5; 0.1; -1.6; -1.7 | — |
| SECONDARY Change From Baseline in Vital Sign Parameter Heart Rate at Week 12 and Week 48 |
0.2; 2.6; 0.5; -0.1 | — |
| SECONDARY Change From Baseline in Vital Sign Parameter Temperature at Week 12 and Week 48 |
-0.03; -0.08; 0.00; -0.06 | — |
Summary
Botulinum toxin A (GSK1358820) is a sterile, purified type A botulinum neurotoxin complex. In Japan, 240 units of botulinum toxin A are approved as a maximum dose per administration for upper limb spasticity. This study is planned to evaluate the effectiveness and safety of 400 units of botulinum toxin A which can help to increase the maximum dose per administration to 400 units from 240 units as the treatment with 240 units is considered insufficient in subjects with post-stroke upper limb spasticity. Approximately 120 subjects will be randomized to receive either 400 or 240 units of botulinum toxin A in double blind phase followed by open-label phase in which 400 units of the study treatment will be injected in both the groups. The study period will be up to 52 weeks, consisting of a screening phase up to 4 weeks, minimum 12-week double blind phase (Part 1), maximum 36- week open-label phase (12 weeks per cycle with 3 treatment phases: Part 2, Part 3 and Part 4).
Eligibility Criteria
Inclusion Criteria
- For screening phase (Day -28 to Day -1): Between 20 and 80 years of age at the time of informed consent (ICF).
- Subjects with at least a 3-month history of upper limb spasticity after the most recent stroke.
- Subjects who have spastic symptoms in the finger (including the thumb), wrist, and elbow flexors whom the investigator considers the injections of 400 units of the product is necessary for the upper limb based on the muscle spasms and the symptoms of the subject.
- Subjects who have a previous treatment history of 240 units of the product for the upper limb at least 16 weeks before screening.
- Subjects who meet following criteria on MAS at screening (Test position : sitting): at least 3 in for the elbow flexors and at least 2 in the finger or wrist flexors.
- Subjects who have severe upper limb spasticity, which deserves to be treated with 400 units of the product in the divided dose and was previously injected 240 units of the product.
- Subjects whom the investigator considers that enrolment in the study poses no problems based on the laboratory data results at screening.
- Subjects who are free from a history of acute decreased lung function (hospitalization with aggravated asthma/ chronic obstructive pulmonary disease (COPD), pneumonia, or signs of pneumonia, or abnormal reactive airway diseases suggested on X-rays) within the last 3 months at screening and have stable pulmonary function (oxygen saturation [SpO2]value is >=95%).
- Body weight >=40 kilograms (kg) at screening.
- Male or female subjects will be included. Male subjects must content to use highly effective contraceptive methods and sperm donation must be avoided. Female subjects who are not pregnant or lactating are considered eligible if at least one of the following criteria is met; non-childbearing potential, women of childbearing potential who content to follow the guidance about contraception during the study period and at least for 3 months after the last dose of the product, no plan of pregnancy during the study period.
- Subjects who have ability to sign their name on the ICF.
- For enrolment in the study (Day 1 [prior to injection]):Subjects who meet the following criteria on MAS score: (Test position : sitting): At least 3 in the elbow flexors and at least 2 in the finger or wrist flexors.
- If centrally acting muscle relaxants, tetracycline antibiotics, anticholinergics, benzodiazepines, or benzamides are given, the dose and regimen must be stable at least for the last 2 months before Day 1; Subjects who can maintain the same dosage and regimens at least in the blind phase after initial injection (dose reductions and discontinuation of the drugs are acceptable in the open-label phase. However, second dose increase, resumption, and or new treatment will not be performed).
- If intrathecal baclofen is given, the dose and regimen must be stable at least for the last 1 month before Day 1; Subjects who can maintain the same dosage and regimens at least in the blind phase after initial injection (intravenous bolus is not acceptable, dose reductions and discontinuation of the drugs are acceptable. However, second dose increase, resumption, and or new treatment will not be performed).
- If antiepileptic agents are given, the dose and regimen must be stable at least for the 1 month before Day 1; Subjects who can maintain the same dose and regimens at least in the blind phase after initial injection (dose reductions and discontinuation of the drugs are acceptable in the open-label phase. However, second dose increase, resumption, and new treatment will not be performed).
- If a physical therapy, occupational therapy, or a static splint on the study involvement upper limbs is given, the frequency and treatment regimen must be stable at least for the last 3 weeks before Day 1; Subjects who can maintain the same dose and regimens at least in blind phase (In the open-label phase, the frequency and treatment regimen can be changed de
Data sourced from ClinicalTrials.gov (NCT03261167). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.