E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
treatment of idiopathic cervical dystonia |
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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 | 10048315 |
E.1.2 | Term | Cervical spasm |
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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 |
The objectives of this study are to evaluate the safety and efficacy of fixed dosages of BOTOX or Dysport in the treatment of idiopathic cervical dystonia in subjects who have been previously treated successfully with equivalent doses of BOTOX |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Subjects with idiopathic cervical dystonia of the predominantly rotational form (i.e., spasmodic torticollis) of minimum duration eighteen (18) months. 2.Moderate-to-severe symptoms as defined by a minimum Toronto Western Spasmodic Torticollis Scale (TWSTRS) severity scale score of 15, with a rotation score of major or equal to 2 and a duration factor of major or equal to 2. 3.Subjects have received successful treatment as determined clinically by both the investigator and patient with 180 220 U BOTOX in each of the last two (2) treatment sessions. 4.Cervical dystonia symptom severity is considered predictable and successfully responsive to BOTOX treatment. 5.The most recent treatment with BOTOX occurred on a date at least 16 weeks prior to study entry, and the subject has received two (2) treatment sessions within the prior 40 weeks with a good clinical response. 6.Outpatient, male or female subjects, of any race, between 18 and 75 years of age. 7.Normal screening laboratory values and negative urine pregnancy test (if applicable). |
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E.4 | Principal exclusion criteria |
1. Symptomatic or non-idiopathic cervical dystonia. 2. Current or previous surgery, peripheral denervation, and/or spinal cord stimulation for the management of cervical dystonia. 3. Previous injections of phenol or alcohol for cervical dystonia. 4. History or evidence of secondary non-response to botulinum toxin type A therapy. 5. Presence of significant anterocollis, retrocollis, or head shift as the principal component of cervical dystonia. 6. Profound atrophy of the muscles or infection or skin problem in the target area(s) of injection. 7. Any other disease that might interfere with neuromuscular function or any uncontrolled systemic disease 8. Current anticoagulant therapy. 9. Failure to meet prohibited/restricted concomitant medication criteria. 10. Subjects planning inpatient surgery or other elective hospitalization during the study period. 11. Females who are pregnant, nursing, or planning a pregnancy (positive urine pregnancy test) or females of childbearing potential, not using a reliable means of contraception. 12. History of treatment with botulinum toxin type A or B of any brand other than BOTOX within the past two (2) years. 13. Allergy or sensitivity to any component of the study medication. 14. Recent history of alcohol or drug abuse (as defined by DSM IV criteria). 15. History of poor cooperation, non-compliance with medical treatment, or unreliability. 16. Subjects currently participating in another investigational drug study or who have participated in an investigational drug study within 30 days of the Baseline Visit unless approved by the sponsor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety Evaluation: Spontaneous Adverse Event Query Subjects will be asked Have you experienced any change in your health since the last study visit? to elicit spontaneous reports of adverse events. Structured Symptom Interview After completing the documentation of spontaneous adverse events, subjects will be given a Structured Symptom Interview (SSI). Any positive reply will require the subject to grade the severity on a 0 to 10 scale. For any evaluation in which the severity grade is at least 2 points higher than the rating at baseline, the adverse event must also be recorded on an adverse event case report form. The Structured Symptom Interview will be administered at every visit through week 10. Dystonia Study Group Dysphagia Interview (DSGDI) All subjects will be asked to complete a detailed Dysphagia Interview (DSGDI). The DSGI will be administered for patients at every visit through Week 10. Efficacy Evaluation: A) PHYSICIAN EVALUATED EFFICACY VARIABLES Physician Assessment of Cervical Dystonia Severity and Toronto Western Spasmodic Torticollis Scale (TWSTRS):: The PHYSICIAN ASSESSMENT OF CERVICAL DYSTONIA SEVERITY and TWSTRS will be conducted at each study visit. Global Assessment of Benefit by Physician: At week 2 and all subsequent visits, the physician will evaluate the subjects benefit from botulinum toxin type A treatment for cervical dystonia using the GLOBAL ASSESSMENT OF BENEFIT BY PHYSICIAN. Comparison of Benefit to Previous Injection: At week 4 and 10, the physician will evaluate the benefit of the current treatment of cervical dystonia with botulinum toxin type A compared to previous treatment. B) PATIENT REPORTED EFFICACY OUTCOME Global Assessment of Benefit by Patient: At week 2 and all subsequent visits, the subjects will rate the benefit from botulinum toxin type A treatment for cervical dystonia using the GLOBAL ASSESSMENT OF BENEFIT BY PATIENT. Patient Analog Assessment of Pain: At each study visit, subjects will be queried regarding their assessment of pain using a Visual Analog Scale rating the pain from no pain to worst possible pain . Comparison of Benefit to Previous Injection: At week 4 and at the exit visit, subjects will be queried regarding their evaluation of benefit of the current treatment of their cervical dystonia with botulinum toxin type A compared to previous treatment. Patient Assessment for Retreatment: At each study visit, subjects will be queried regarding their need for another injection of botulinum toxin type A for cervical dystonia. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |