E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spasticity and Associated Focal Spasticity |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041416 |
E.1.2 | Term | Spasticity |
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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 effectiveness of BOTOX® + Standard of Care (SC) versus placebo + SC for the treatment of adult post-stroke focal spasticity as measured by the number of patients in each arm who achieve their principal functional goal as determined by the physician. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the effectiveness of BOTOX® + SC versus placebo + SC for the treatment of adult post-stroke focal spasticity; - as measured by the number of patients in each arm who achieve their functional goal as determined by the patient. - and as measured by the level of functional goal as determined by the patient. •Time to reach functional goal attainment as determined by the physician and patient. •To evaluate and compare improvement in patient’s quality of life when treated with BOTOX® + SC versus placebo + SC. •To collect resource use data from actual clinical practice in the treatment of patients in rehabilitation centres and specialised centres. •To evaluate and compare level of resource use of patients on BOTOX® + SC versus placebo + SC. •To evaluate and compare the cost, cost-effectiveness and cost-utility of BOTOX® + SC versus placebo + SC. •To identify drivers of use of resources and cost. •Occurrence of adverse events (AEs) during the study. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female patients between 18 and 85 years of age 2.Patients with stroke due to a primary cerebral haemorrhage/ infarction, subarachnoid haemorrhage producing an upper motor syndrome affecting one body side which results in a hemi-paralysis/plegia 3.Patients suitable for botulinum toxin type A (BOTOX®) 4.Patients with documented focal/multifocal problems of spasticity in the upper and/or lower limbs and for who functional gains are anticipated after treatment with BOTOX® + SC
•Patients treated for upper limb spasticity: evidence of preserved antagonist function and at least one item of the REsistance to PAssive movement Scale (REPAS) with a score of at least 1 at the relevant joint(s) for the primary endpoint •Patients treated for lower limb spasticity: evidence of preserved standing/ambulation function and at least one item of the REPAS with a score of at least 1 at the relevant joint(s) for the primary endpoint 5.Patients with spasticity, as defined in criterion #4 above, caused by a stroke that happened 3 months or more before the Screening visit 6.Female patients either surgically sterile (has had tubal ligation, documented bilateral oophorectomy and/or hysterectomy), postmenopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom the result of a urine pregnancy test is negative and agree to use birth control (e.g. hormonal contraception [estrogen or progesterone agents], intrauterine contraceptive device, double barrier methods [condom with spermicide, diaphragm with spermicide, or male condom and diaphragm], or total sexual abstinence) during the study 7.Patients able to communicate effectively, with the help of a third person completing answers on their behalf (when required) 8.Patients willing and able to come to each study protocol visit and answer questions by phone on a monthly basis, possibly with the assistance of a caregiver 9.Patients willing and able to provide a signed and dated written informed consent |
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E.4 | Principal exclusion criteria |
1.Patients with fixed contracture as a result of spasticity in the upper or lower limb planned to be treated 2.Patients with other causes of spasticity (e.g. multiple sclerosis, spinal cord injury, etc.) 3.Patients who have been previously treated with botulinum toxin or phenol nerve block in the limbs to be injected during this trial 4.Patients requiring concomitant use of intrathecal baclofen or phenol nerve block at any point during the study; patients requiring systemic aminoglycoside antibiotics or spectinomycin during the period from at least 3 days before until 6 weeks after injection of study medication. 5.Patients who are currently taking part in any other clinical trial or have taken part in a clinical trial of a new chemical entity within 6 months prior to Screening 6.Patients with a Mini-Mental State Examination (MMSE) < 20 7.Patients not sufficiently motivated to participate in the study as determined by an Apathy Evaluation Scale score > 40 8.Patients with known medical conditions (e.g. cardiac condition, cancer, etc.) that would affect their ability to benefit from treatment or to complete the study 9.Patients with a known hypersensitivity to any botulinum toxin or to any of the excipients of BOTOX® (i.e. Human serum albumin) 10.Patients with myasthenia gravis or Eaton Lambert Syndrome 11.Patients with infection at the proposed injection site(s) |
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E.5 End points |
E.5.1 | Primary end point(s) |
•comparison of the number of patients in each of the two treatment arms who achieve their principal active functioning goal (i.e. a score of 0 to +2 inclusive), as determined by the physician, at 10 weeks after the second injection (between 22 and 34 weeks) or at 24-week visit or at time of withdrawal if no second injection has been conducted
Goal attainment will be measured using the following 6-point Likert scale:
Score Outcome -3 Worse than start -2 Equal to start: the patient’s initial condition; no change -1 Less than expected: slight improvement, but below the defined therapeutic goal 0 Expected goal: attains the defined therapeutic goal +1 Somewhat more than expected: improvement slightly exceeds the defined therapeutic goal +2 Much more than expected: improvements clearly exceed the defined therapeutic goal
For each patient, Two functional goals will be set: 1) Principal active functional goal 2) Secondary active or passive functional goal
For each patient, a principal active functional goal will be determined during Baseline visit by the patient and the investigator together, using the following list: •Improvement in active function of the upper limb to achieve a personal goal (i.e. dressing, writing/typing, feeding, washing, wheelchair propulsion, other, please specify) or •Improvement in active function in lower limb to achieve a personal goal (i.e. ability to sit, assisted transfers, independent transfers, wheelchair propulsion, ambulation, climbing stairs, other, please specify) |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
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.8.3 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
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 | Information not present in EudraCT |
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 |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |