E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Poststroke spasticity involving the muscles of the elbow and shoulder in adult patients |
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E.1.1.1 | Medical condition in easily understood language |
Poststroke spasticity involving the muscles of the elbow and shoulder in adult patients |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041416 |
E.1.2 | Term | Spasticity |
E.1.2 | System Organ Class | 100000004852 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042244 |
E.1.2 | Term | Stroke |
E.1.2 | System Organ Class | 100000004852 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048970 |
E.1.2 | Term | Arm spasticity |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and efficacy of repeated doses of 300 U and 500 U BOTOX
for the treatment of adult upper limb spasticity. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For patients who directly rollover from Study 191622-127:
• patient has fulfilled Study 191622-127 exit criteria: either met qualification for retreatment criteria or completed week-16 visit (if they never qualified for retreatment)
• patient has not experienced an adverse event or developed a medical condition (eg, breathing difficulties) that, based on the investigator’s clinical judgment, may indicate an unacceptable safety risk for additional BOTOX treatments
• patient has not experienced a treatment-related serious adverse event in Study 191622-127
• negative urine pregnancy test for all female patients of childbearing potential
For de novo patients:
• male or female aged ≥ 18 to ≤ 80 years
• score of ≥ 2 on the MAS-B in the elbow flexors at both the screening and day 1 visits
• score of ≥ 2 on the MAS-B in the shoulder adductors (of the same limb with elbow spasticity) at both the screening and day-1 visits
• minimum body weight of 50 kg (110 pounds) at the screening visit
• in the opinion of the investigator, the patient has sufficient spasticity to warrant a total BOTOX dose of 500 U divided into the muscles of the elbow and shoulder of a single upper limb
• negative urine pregnancy test for all female patients of childbearing potential |
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E.4 | Principal exclusion criteria |
• patients with spasticity in the contralateral upper limb that requires treatment, in the opinion of the investigator
• presence of fixed contractures of the study muscles of the elbow or shoulder
• previous surgical intervention, phenol block, ethanol block, or muscle afferent block for the treatment of spasticity in the study muscles of the elbow or shoulder within 12 months prior to the day 1 visit or planned during the study
• presence or history (within 12 months prior to the day 1 visit) of aspiration pneumonia, recurrent lower respiratory tract infections, uncontrolled asthma, uncontrolled chronic obstructive pulmonary disease, or significantly compromised respiratory function, that may indicate a vulnerable respiratory state, per the investigator’s clinical judgment
• presence or history (within 12 months prior to the day 1 visit) of aspiration or a condition(s) that, in the investigator’s opinion, may put the patient at increased risk of aspiration (eg, significant drooling, chronic dysphagia [difficulty swallowing] requiring changes in diet)
• intraarticular injection of corticosteroids or anesthetics in the elbow or shoulder of the study limb within 3 months prior to the day 1 visit or planned during the study
• any medical or neurological condition that may put the patient at increased risk with exposure to BOTOX, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant diseases or concomitant mediations that might interfere with neuromuscular function
• patient has a condition or is in a situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient’s participation in the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The key efficacy measure is MAS-B of the treated muscle group(s) of the
upper limb |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The MAS-B change from baseline to each post randomization visit |
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E.5.2 | Secondary end point(s) |
No secondary endpoints specified. All Efficacy and Safety variables will be summarised. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy and safety variables will be evaluated at each measured timepoint. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
different dosage of test product |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Czech Republic |
Germany |
Hungary |
Korea, Republic of |
Poland |
Russian Federation |
Singapore |
Thailand |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |