E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relief of central neuropathic pain in subjects with multiple sclerosis (MS) |
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MedDRA Classification |
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 efficacy of Sativex® compared with placebo, when added to existing treatment regimens, in relieving neuropathic pain in subjects with MS.
Phase B (Open label/Randomised withdrawal phase) - To investigate the maintenance of efficacy after long term treatment with Sativex in the indication of central pain in multiple sclerosis. Assesment of the abscence or ocurrence of withdrawal symptoms. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of Sativex® compared with placebo on:· -Secondary measures of pain relief -Brief Pain Inventory (BPI) -Subject Global Impression of Change· -Sleep quality
To assess the safety and tolerability of Sativex® |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects meeting the following criteria will be considered eligible for this study: 1. Subjects aged 18 years or above. 2. Diagnosed with any disease sub-type of multiple sclerosis (MS) of at least two years duration. 3. Central neuropathic pain (CNP) due to MS, of at least three months and which is expected to remain stable for the duration of the study. 4. Subject has at least moderate CNP, which is defined by: NRS pain scores on all of baseline days B2 to B7 have been recorded, via the IVRS, by the subject and sum to at least 24. 5. Subject fulfils at least one of the two criteria below. Subject must be either: - Currently established on a regular dose of analgesic therapy for their CNP - Previously tried and failed or could not tolerate analgesic therapy for their CNP. 6. Stable medication regimen for at least 2 weeks prior to study entry, for all medications that may have an affect on neuropathic pain, except paracetamol/acetaminophen. 7. Subject is willing to stop taking their own paracetamol/acetaminophen or paracetamol/acetaminophen containing medications and start using study medication paracetamol/acetaminophen as required (prn) for the duration of the study. 8. Subject is willing to maintain a stable dose of medications that may have an effect on neuropathic pain, other than study medication and paracetamol/acetaminophen, for the duration of the study. 9. If the subject is taking disease modifying medication this must be at a stable dose for 3 months prior to the screening visit.
Part B Visit 6 - Study entry prior to receiving open label study medication.
For inclusion into Part B of the study, subjects must fulfil ALL of the following criteria: 1. Subject has participated in GWMS0501, is currently ongoing in the study (i.e., subject is still receiving study treatment) and has completed the study up to Visit 6. 2. Subject has complied with all of the study requirements to-date. 3. Subject has at least a 90% compliance rate in the completion of the daily IVRS calls. 4. Subject has a mean dose of three or more sprays per day over the seven days prior to visit 6. 5. Subject has shown tolerability to the study medication in this study. 6. Subject is willing and able (in the investigators opinion) to comply with all study requirements, including the completion of the daily IVRS calls.
Part B Visit 6c - Following the 12 week open label treatment phase before entry into the double-blind randomised withdrawal phase.
For inclusion in to the randomised withdrawal phase of the study, subjects must fulfill ALL of the following criteria: 7. Subject is currently ongoing in Part B of GWMS0501 (i.e., subject is still receiving study treatment) and has completed the study up to visit 6c. 8. Subject has complied with all of the study requirements to-date. 9. Subject has at least a 90% compliance rate in the completion of the daily IVRS calls. 10. Subject has a mean dose of three or more sprays per day over the seven days prior to visit 6c. 11. Subject is willing to maintain a stable medication regimen for all medications that may have an effect on neuropathic pain. 12. Subject has shown tolerability to the study medication in this study. 13. Subject is willing and able (in the investigators opinion) to comply with all study requirements, including the completion of the daily IVRS calls.
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E.4 | Principal exclusion criteria |
The subject may not enter the study if ANY of the following apply: 1. Subjects whose identified pain is likely to be of a nociceptive, musculoskeletal (including spasms) peripheral neuropathic or psychogenic origin, or is due to trigeminal neuralgia. 2. Other pain which is not of a central neuropathic origin thought by the investigator to be of a nature or severity to interfere with the subject’s assessment of neuropathic pain due to MS. 3. Subjects medical history suggests that relapses/remission are likely to occur during the study (the next 15 weeks) which are expected to influence the subjects CNP. 4. Currently receiving a prohibited medication and unwilling to stop or comply for the duration of the study. 5. Currently using or has used recreational cannabis, medicinal cannabis (including Sativex®), or synthetic cannabinoid based medications within 3 months prior to study entry and unwilling to abstain for the duration for the study. 6. Any known or suspected history of: - or family history of schizophrenia, other psychotic illness; - alcohol or substance abuse - epilepsy or recurrent seizures - hypersensitivity to cannabinoids 7. Significant cardiac, renal or hepatic impairment. 8. If female, is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter. 9. Travel outside the country of residence planned during the study. 10. Subjects who have received an IMP within the 12 weeks before the screening visit.
Part B Visit 6 and all subsequent Part B visits:
The subject may not enter Part B of the study if the following applies: 1. The subject has experienced or is currently experiencing any adverse events or untoward medical occurrences which, in the opinion of the investigator, would prevent them from safely participating in part B of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the mean pain due to MS NRS score taken from the daily IVRS diaries over the last seven days at the end of treatment during the evaluable period (usually week 14).
The variable for analysis will be the proportion of subjects showing a response (defined as an improvement of 30% or more in their mean pain NRS score from baseline to the primary end point).
Part B
The primary endpoint is the time to treatment failure from the randomised phase of Part B of the study. |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
Part B - 12 week open label and 4 week, double blind, placebo controlled, randomised withdrawal |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
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 |