E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
We aim to achieve a study population of 30 patients (male or female, 18 to 65 years of age) suffering from major depressive disorder (DSM IV criteria). Depressive symptoms should be present for at least 3 weeks (Hamilton depression rating scale >17). Patients will be examined on admission and after 6 weeks of treatment with duloxetine. Only patients without any psychiatric medical treatment for 8 weeks will be considered. 30 controls matched with respect to age and sex will be included. |
|
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 test the hypothesis that duloxetine normalizes increased electrical and thermal pain thresholds to control levels within 6 weeks of treatment and improves reaction to A-delta and C-fiber laser stimulation in depressed subjects similar to controls. |
|
E.2.2 | Secondary objectives of the trial |
To test the hypothesies that duloxetine prolongs the onset latency (in seconds) of ischemic pain in depressed patients up to levels of control patients within 6 weeks of treatment, indicating profound analgesic effects on deep somatic pain.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject inclusion criteria:
All participants:
• Ability to understand and transform the explanations and advices of the investigator. • Signature on a legally effective consent form
Patients
• Major depressive disorder (MDD) according to DSM IV criteria • Depressive symptomatology for at least 3 weeks (Hamilton depression rating scale, (HAM-D-21 >17)) • Male or female patients • 18 years to 65 years of age
Annotation: Women of the patient group of child-bearing age will only be enclosed into the study after pregnancy has been excluded using specific pregnancy tests. Furthermore they have to have a sufficient contraception method with a scientifically proven low failure rate (Pearl-Index of < 1 %). Accepted are hormonal contraception (per os or intramuscular), operative sterilisation, hysterectomy, bilateral ablation of the ovaries, vasectomy of the male sexual partner, sexual abstinence, post menopause (WHO definition: retrospective 12 consecutive months of amenorrhoea). In case of doubtful effectiveness of the hormonal contraception, due to interfering comedication, additional nonhormonal contraception is essential (such as spermatocidal agents, intrauterine implantations).
|
|
E.4 | Principal exclusion criteria |
Patients exclusion criteria:
• Age below 18 years or above 65 years • Pregnancy or lactation • Participation in another clinical trial in the previous 8 weeks • Patients scoring higher than ‘2’ on the present pain intensity scale (PPI; McGill Pain Questionnaire (Melzack, 1975)). • Serious and unstable medical illnesses (e.g. heart, liver or kidney disease) • Other psychiatric illnesses not allowed by the protocol, for example, schizophrenia, schizoaffective disorder, bipolar disorder, mania, anxiety disorder, eating disorders or personality disorders • Current substance abuse or dependence disorders • Patients with severe liver diseases (such as hepatitis, icterus), cave with comedication of liver damaging medications • Elevated serum liver enzymes (above 2-fold upper reference range) • Patients with severe renal disease (creatinine clearance < 30 ml/min, calculated according to Cockroft and Gault) • Hyponatremia (serum sodium concentration <134 mmol/l) • Past medical history of uncontrolled high blood pressure / actual severe hypertension (systolic blood pressure > 160 mmHg) • Known mydriasis, elevated intraocular pressure, predisposition to narrow angle glaucoma in the past or present medical history • Past or present medical history of epilepsy • Predisposition for bleedings • Therapy with anticoagulants (heparin, heparinoids, hirudin, cumarin derivates, Warfarin) and thrombocyte aggregation inhibitors (acetyl salicyl acid (ASS), clopidogrel, combination from ASS and dipyridamol (Aggrenox®), ticlopidin) • Hypersensitivity against duloxetine or other components of the duloxetine capsule, such as sucrose • Hereditary Fructose intolerance • Glucose-Galactose malabsorption • Sucrase-Isomaltase deficiency • Comedication with antipsychotic agents, opioids, phenobarbital, sedative histamine antagonists • Comedication with non-selective, irreversible MAO (monoaminooxidase) inhibitors, selective reversible MAO inhibitors, at present or in the last 14 days • Comedication with other antidepressants (especially SSRI´s, other SNRI´s, tricyclic antidepressants), St. John´s wort (Hpericum perforatum), venlafaxin, triptans, pethidin, tramadol, tryptophan, substances which are mainly metabolised over CYP2D6 (such as, risperidon, flecainid, propafenon, metoprolol), tolterodin • Comedication with potent CYPA2 inhibitors (such as fluvoxamin, ciprofloxacin, enoxacin)
Control subjects exclusion criteria:
• Age below 18 years or above 65 years • Participation in another clinical trial in the previous 8 weeks • Control subjects scoring higher than ‘2’ on the present pain intensity scale (PPI; McGill Pain Questionnaire (Melzack, 1975)). • Serious and unstable medical illnesses (e.g. heart, liver or kidney disease) • All psychiatric illnesses, e.g. affective disorders such as depression, bipolar disorder or anxiety disorder, schizophrenia, schizoaffective disorder, eating disorders, personality disorders • Current substance abuse or dependence disorders
Lorazepam up to 3 mg/d is allowed, but needs to be discontinued 2 two days before pain assessment. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Improvement of A-delta and C-fibre stimulation reaction in MDD. Significantly increased electrical and thermal pain thresholds / tolerances and decreased ischemic pain thresholds / tolerances after 6 weeks of duloxetine treatment in MDD patients. |
|
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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Antinociceptive action of duloxetine |
|
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 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
| |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |