E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
post-stroke spasticity of the upper limb |
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E.1.1.1 | Medical condition in easily understood language |
increased muscle tension / uncontrollable muscle stiffness in the arm after a stroke |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058977 |
E.1.2 | Term | Spastic paresis |
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 investigate the efficacy and safety of NT 201 compared to placebo in the first double-blind cycle, and in 3 subsequent open-label treatment cycles with a total exposure duration of 48 weeks in Botulinum toxin [BTX] treatment-naïve subjects with post-stroke spasticity in the upper limb. A fixed total dose of 400 units [U] NT 201 per cycle will be injected at a fixed interval of 12 weeks between injections. |
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E.2.2 | Secondary objectives of the trial |
there are no secondary objectives |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age from 18-80 yrs
Upper limb spasticity
Time since stroke greater than 3 months
Need for 400 U Botulinum toxin type A |
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E.4 | Principal exclusion criteria |
Body weight below 50kg
Fixed contractures of the upper limb
Generalized disorders of muscle activity like Myasthenia gravis that preclude use of Botulinum toxin type A
Infection at the injection site |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in Ashworth Scale Score of primary target clinical pattern. Primary target clinical pattern will be defined by the investigator for each subject individually at baseline visit (week 0) and will be one of the following: flexed wrist, clenched fist or flexed elbow.
Co-Primary end point: Investigator’s Global Impression of Change |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Response rates for the primary target clinical pattern at all post-baseline visits for subjects with an improvement (=reduction) of at least 1 point from baseline measured by the Ashworth Scale.
• Response rates in each treated muscle group (elbow, wrist, and finger flexors as well as thumb muscles and forearm pronators) at all post-baseline visits for subjects with an improvement (=reduction) of at least 1 point from baseline measured by the Ashworth Scale.
• Changes from baseline to all post-baseline visits in Ashworth Scale Score for each treated muscle group
• Changes from baseline to all post-baseline visits in Disability Assessment Scale (primary therapeutic target and additionally all 4 items regardless of chosen primary therapeutic target) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
India |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
|
end of trial is defined as 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 | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |