E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spasticity associated with multiple sclerosis |
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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 | 10028335 |
E.1.2 | Term | Muscle 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 determine the long-term safety and tolerability of AV650 in subjects with spasticity associated with MS. |
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E.2.2 | Secondary objectives of the trial |
To determine preliminary efficacy of AV650 as compared to placebo in subjects with spasticity associated with MS.
To determine the pharmacokinetic (PK) profile of AV650 administered 150 mg TID or 300mg TID in subjects with spasticity associated with MS. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects between 18 and 70 years of age (inclusive) 2. Signed and dated informed consent 3. Definite MS as per Poser or MacDonald Criteria (either relapsing remitting or secondary progressive course) 4. Expanded Disability Status Score (EDSS) from 3.0 to 6.5 (inclusive) at Screening 5. Stable MS for at least 30 days before screening 6. Female of child bearing potential and male subjects whose partner is of child bearing potential who are willing to ensure that they or their partner use effective double-barrier contraception during the study and for 90 days thereafter 7. If female, be neither pregnant nor nursing (Confirmation that the subject is not pregnant must be established by a negative serum hCG pregnancy test at baseline.) 8. Significant spasticity in at least two muscle groups defined as a score of 2 or more on the Ashworth scale for each muscle group 9. If a subject is on anti-spastic treatments, the dosage, frequency, and route of administration must be stable for at least 30 days before Screening 10. If a subject is on MS treatments, the dosage, frequency, and route of administration must be stable for at least 30 days before Screening
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E.4 | Principal exclusion criteria |
1. Subjects who have participated in another research study within 90 days of Screening 2. Significant changes in anti-spasticity medications (dosage, frequency, or route of administration) within 30 days of Screening 3. Known hypersensitivity to tolperisone HCl, its components, or other lidocaine/lidocaine-like products 4. Use of tolperisone within 30 days of Screening 5. Significant changes in MS treatments (dosage, frequency, or route of administration) within 30 days of Screening 6. Spasticity due to neurological disorders other than MS 7. Any psychiatric disorder or cognitive impairment that precludes fully informed consent or safe participation in the study 8. Subjects who have suffered an acute relapse of MS or who continue to suffer from an acute relapse of MS within 90 days of Baseline 9. History of alcohol or substance abuse within one year of Screening 10. Concurrent clinically significant immunologic, pulmonary, renal, hepatic, or endocrine disease and/or other unstable or major disease other than MS 11. Clinically significant cardiovascular disorders, such as ischemic heart disease, arrhythmias, poorly controlled hypertension, or acute myocardial infarction 12. QT prolongation greater than 480 msec or greater than 450 msec if accompanied by a partial bundle branch block, or other ECG abnormality in the judgment of the Investigator 13. Diastolic blood pressure <50mmHg or >105mmHg; heart rate <50 beats per minute (bpm) or >110bpm, after 3 minutes in a sitting position; heart rate by ECG <50bpm or >110bpm 14. History of epilepsy (except childhood febrile seizures) 15. Current malignancy or history of malignancy that has not been in remission for more than five years, except basal cell skin carcinoma and cervical cancer (with documentation of normal pap smears after definitive treatment) 16. Female subject who is pregnant, nursing, or planning pregnancy during the course of the study 17. Scheduled elective surgery or other procedures requiring general anesthesia during the study 18. Subject who is terminally ill in the judgment of the Investigator 19. Subject who is inappropriate for placebo medication in the judgment of the Investigator 20. Systemic corticosteroid therapy within 28 days of randomization, with the exception of inhaled medications for asthma 21. Exacerbation of MS within 30 days of Baseline. 22. Regular levo-dopa therapy within 7 days of randomization 23. Subjects taking antiarrhythmic medications 24. Donation of blood during the study
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E.5 End points |
E.5.1 | Primary end point(s) | |
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | 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
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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 | |
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 | 3 |