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 |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054095 |
E.1.2 | Term | Neuropathic pain |
E.1.2 | System Organ Class | 100000004852 |
|
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. |
|
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
• Distribution of responder at visits E6, E7, E8 and E9 by dosage group
• 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
• Adverse Events
• Safety laboratory parameters
• Vital parameters / weigh
Criteria in follow-up phase 3:
• Retrospective pain assessment for the past 4 weeks (11-NRS)
• Pain-related sleep interference
• SF-36 (QOL-questionnaire)
• CGI, Item A
• Adverse events
• Assessment of dependence
• Safety laboratory
• Vital parameters
• Global assessment of tolerability
• ECG
• EDSS |
|
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
• 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)
Inclusion criteria for follow-up phase 3:
• Complete participation in main study, from visit E1 to visit E20
• Termination of study phase 2 with visit E20a taking place not more than 7 days later.
Exception for all patients with E20 before implementation of Amendment No 11: Termination of study phase 2 with visit E20a taking place not more than 1 month later
Exception for all patients with E20 taking place after 31.07.2008 and E20a taking place between December 1st and December 17th, 2008.
• Treatment is still indicated as per the investigator’s discretion
• Negative pregnancy test for female patients of childbearing potential at visit E20 or E20a respectively
• Willingness and capability to pass all required examinations over the entire time of the follow-up phase 3
|
|
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
Exclusion criteria for follow-up phase 3:
• Critical adverse events during time interval between E20 and E20a including:
─ Schizoid symptoms
─ Mania or bipolar affective disorder
─ Epilepsy
• Abuse of or dependence on Dronabinol
• Reevaluation of main criteria such as
─ Advanced renal insufficiency (creatinine >2,2mg/100ml)
─ Advanced hepatic insuffiency (SGOT/ASAT; SGPT/ALAT >2,5 x upper normal value)
─ Known severe cardiac diseases (e.g. cardiac insufficiency NYHA IV, severe arrhythmia, severe CHD, myocardial infarction within the last 6 months)
─ Known HIV-infection
─ Known alcohol, narcotics or drug abuse
─ Unwillingness to abstain from use of marihuana
─ Concurrent participation in other studies
─ Patients with major peripheral pain syndromes
─ Legal incompetence or limited legal competence
─ Patients who do not sign a consent form after thorough medical consultation |
|
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 score taken from the initial patient assessment and the daily patient recordings of his/her average chronic pain on the 11-point NRS within a maximum of 16 weeks |
|
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 | 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
|
|
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 | 1 |
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 | 1 |