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 |
|
E.1.1.1 | Medical condition in easily understood language |
Poststroke spasticity involving the muscles of the elbow and shoulder in adult patients |
|
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 |
|
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 |
|
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 |
|
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 safety and efficacy of BOTOX 300 U and 500 U in the treatment of spasticity
involving the muscles of the elbow and shoulder of adult poststroke patients. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• male or female, ≥ 18 to ≤ 80 years of age at screening visit with upper limb spasticity due to stroke
• MAS-B score of ≥ 3 in the elbow flexors at both screening and day-1 visits
• MAS-B score of ≥ 3 in the shoulder adductors (of the same limb with elbow flexor spasticity) at
both 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 among elbow and shoulder muscles of the same limb |
|
E.4 | Principal exclusion criteria |
• patients with spasticity in the contralateral upper limb that requires treatment
• 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 in either 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 an increased risk for 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 medications that might interfere with
neuromuscular function |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in the MAS-B elbow flexors. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 6. The primary variable will also be evaluated at all other post-treatment visits. |
|
E.5.2 | Secondary end point(s) |
• MAS-B of the shoulder adductors (change from baseline)
• Pain scale (11-point numeric rating scale [NRS]) (change from baseline)
• Disability Assessment Scale (DAS): principal therapeutic intervention target (PTIT)
(change from baseline) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Week 6
• The secondary variables will also be evaluated at all other post-treatment visits |
|
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 26 |
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 |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
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 |