E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with multiple sclerosis associated with central neuropathic pain |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054095 |
E.1.2 | Term | Neuropathic pain |
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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 objective of this study is to examine whether the long-term administration of dronabinol leads to a statistically and clinically significant reduction of the chronic pain in patients with MS associated with central neuropathic pain. |
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E.2.2 | Secondary objectives of the trial |
• Distribution of frequency, duration, and intensity of episodes with acute pain attacks • Distribution of responder at visits E6, E7, E8 and E9 (A responder is defined as a patient experiencing at least a 30% reduction on pain intensity as compared to baseline) • Distribution of responder at visits E6, E7, E8 and E9 by dosage group (7.5, 10, 12.5, 15mg daily dose) • NRS pain relief • Pain- related sleep interference • Length of treatment period • Time to first response • SF-36 (QOL-questionnaire) • Clinical global impression • Intake of rescue medication • The primary endpoint and all secondary endpoints will be additionally evaluated at study end (visit E20) • Adverse Events • Safety laboratory parameters • Vital parameters / weigh
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Outpatients aged 18 to 70 years • Patients who meet the McDonald diagnostic criteria for definite MS • Patients with an EDSS score ≥3 and ≤8 • Outpatients aged 18 to 70 years • Patients who meet the McDonald diagnostic criteria for definite MS • Patients with an EDSS score ≥3 and ≤8 • Patients who are in a stable phase of MS • Patients with MS associated with central neuropathic pain for at least 3 months • Patients with central neuropathic pain characterized by pain in a body territory with abnormal sensation to pinprick, touch, or temperature evaluated by the bedside • Patients with moderate to severe pain (= pain intensity score of at least 4 on the 11-point Likert Numerical Rating Scale (NRS) at the maximal pain site)
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E.4 | Principal exclusion criteria |
• Patients experiencing a relapse ─ within 30 days prior to screening, or ─ during the run-in phase, or ─ at randomization • Patients with mania or bipolar affective disorder • Schizoid symptoms or history of schizophrenia or schizophrenia in the family anamneses • Patients with epilepsy • Patients with trigeminal neuralgia • Patients with severe cardiac diseases • Advanced renal insufficiency (creatinine >2,2mg/100ml) • Advanced hepatic insufficiency (SGOT/ASAT; SGPT/ALAT >2,5 x upper normal value) • Treatment with dronabinol within the last 12 months • Use of marihuana within the last 4 weeks and unwillingness to abstain from the use of marihuana for the duration of the study • Known hypersensitivity to tramadol and excipients of Tramal® (in Germany and Austria) or Nobligan® (in Denmark) capsules
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of efficacy will be the mean change of baseline pain severity scores taken from the daily patient recordings of his/her average chronic pain on the 11-point Numerical Rating Scale (NRS) within a maximum of 16 weeks. |
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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 | 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 | 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) | 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 | Yes |
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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 7 |
E.8.9.1 | In the Member State concerned days | |
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 | 7 |