E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic pain: neuropathic pain and fibromyalgia
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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 | 10033371 |
E.1.2 | Term | 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 |
To analyse chronic pain patients with and without neuropathic pain with respect to: 1) Effect of a balanced serotonergic and noradrenergic reuptake inhibitor (duloxetine) on pain, anxiety and depression measures. 2) Relation between character and quality of pain, depression and anxiety. 3) Time course for changes in pain, anxiety and depression following treatment.
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients 18-75 years of age.
2. Patients with neuropathic pain. Diagnoses: peripheral nerve lesion, polyneuropathy in feet, spinal root compression, and post-herpetic neuralgia.
3. Patients with non-neuropathic pain. Diagnosis: fibromyalgia.
4. Daily pain present > 6 months.
5. Mean weekly pain score > 4 on an 11-point Likert scale the last week of the screening period.
6. Treatment with antidepressants (TCA, SSRI, SNRI, MAOI or others), gabapentin, pregabalin, and carbamazepine must be stopped at least two weeks before treatment phase.
7. Efficient contraception (women in the fertile age).
8. Written and verbal informed consent and letter of authority.
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E.4 | Principal exclusion criteria |
Exclusion criteria: Before the beginning of the study 1. Hypersensitivity to the active substance or to any of the excipients in duloxetine.
2. Severe renal impairment (creatinine clearance<30 ml/min.)
3. Liver disease resulting in hepatic impairment.
4. Comcomitant use of nonselective, irreversible or selective, reversible Monoamine Oxidase Inhibitors (MAOIs) within at least 14 days of discontinuing treatment with MAOI. Based on the half-life of duloxetine, at least 5 days should be allowed after stopping duloxetine before starting an MAOI.
5. Comcomitant use of fluvoxamine, ciprofloxacin or enoxacine (i.e. potent CYP1A2 inhibitors) since the combination results in elevated plasma concentrations of duloxetine.
6. Comcomitant use of serotonergic medicinal products: SSRI´s, TCA´s like clomipramine or amitriptyline, john´s wort (hypericum perforatum), SNRI like venlafaxine or triptans, tramadol, pethidine and tryptofan (risk of serotonine syndrome).
7. Comcomitant use of anticoagulants, medical products known to affect platelet function, diuretic medication, alcohol and sedative medicinal products (e.g. benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamines), flecainide, propafenone and metoprolol (risk of interaction).
8. Serious or unstable medical illness (e.g. apoplexy, Alzheimer’s disease, affected platelet function, dehydration, epilepsy, hypertension, haemodialysis, hyponatremia, fructose intolerance, glucose-galactose malabsorption, haemophilia, increased intraocular pressure, ischemic pain, uncontrolled narrow-angle glaucoma, Raynaud´s phenomenon, sucrose-isomaltase insufficiency, and previous case of anaphylactic shock reaction). Confirmed by medical history and, if possible, compared to medical records.
9. Current and previous diagnosis of mania, bipolar disorder, psychosis, severe agitation, imminent deliria, suicidal ideation, suicidal behaviour, alcohol or drug dependence (ICD-10). Confirmed by psychiatrical history and, if possible, compared to psychiatrical or medical records.
10. Prior participation in a duloxetine study.
11. Pregnancy and lactation.
After the beginning of the study (discontinuation)
1. Development of serious adverse effects or hypersensitivity to the active substance or to any of the excipients in duloxetine.
2. Hamilton Depression score > 18 or Major Depression Inventory > 39.9. (Antidepressant medication will be initiated immediately).
3. Suicidal ideation and suicidal behaviours (treatment will be initiated immediately).
4. Pregnancy.
5. Lack of compliance with regard to intake of study medication and diary records.
6. Intake of pain and/or antidepressant medication not included in the study.
7. The patient cannot co-operate during the examination.
8. The patient wishes to leave the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measure will be the reduction in the mean daily pain score as measured by VAS based on measures in the last week of treatment.
Secondary efficacy measures include Psychological distress (Symptom Checklist-92), Hamilton Depression and Anxiety Rating Scale, Major Depression Inventory, Anxiety Inventory GAD-10, McGill Pain Questionnaire, Patient’s Global Impression of Improvement, assessment of sleep on an 11-point Likert Scale, thermal and pressure pain thresholds, pain areas, capsaicin test, response to cold pressor test and daily intake of concomitant medication during the trial. |
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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 | No |
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) | 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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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
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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 | |
E.8.9.1 | In the Member State concerned days | |