E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic Peripheral Neuropathy |
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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 | 10012683 |
E.1.2 | Term | Diabetic peripheral neuropathy |
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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 assess the long-term safety and tolerability of [S,S]-RBX in patients with DPN. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of long-term treatment with [S,S]-RBX on neuropathic pain and health-related quality of life in patients with DPN.
To assess the effect of long-term treatment with [S,S]-RBX on the use of pain-related medications for the management of DPN.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Male or female of any race at least 18 years of age. · Female patients must be postmenopausal, or surgically sterilized, or (if they are of childbearing potential) they must be nonpregnant and nonlactating and must be using appropriate methods of contraception (including barrier or hormonal method). Women of childbearing potential must have a confirmed negative urine pregnancy test at the screening visit (V1) and at the randomization visit (V2). · Diagnosis of type 1 or 2 diabetes mellitus (by American Diabetic Association Clinical Practice Recommendations diagnostic criteria www.diabetes.org) for at least 1 year; Hemoglobin A1c levels of ≤11% at V1 (with fluctuations of ≤1% in the three months prior to this, established by comparison of V1 HbA1c result with an HbA1c result obtained between 6-12 weeks before V1) and at V1 completion of a diabetes treatment checklist (see Appendix A), demonstrating optimal diabetic control. · Diagnosis of painful, distal, symmetrical, sensorimotor polyneuropathy, which is due to diabetes, for at least 1 year. · Patients at V1 must have a score ≥40 mm on the Pain Visual Analogue Scale (VAS). · Normal chest x-ray within 1 year prior to V1; or stable x-ray defined as no clinically significant change from previous exam (if none available, x-ray must be taken at V1). · Patients must be able to understand and cooperate with trial procedures, and have signed a written informed consent prior to entering the trial.
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E.4 | Principal exclusion criteria |
· Malignancy within the past 2 years with the exception of basal cell carcinoma. · Patients with significant hepatic impairment (i.e. AST/ALT > 2x ULN, Total bilirubin >2 x ULN). · Clinically significant abnormal 12-lead ECG (in the opinion of the investigator). · Neurological disorders unrelated to diabetic neuropathy that may confuse the assessment of neuropathic pain. · Any pain or other condition that may confound assessment or self-evaluation of the pain due to diabetic neuropathy. · History of chronic hepatitis B or C, acute hepatitis A, B or C within the past 3 months, or HIV infection. · Skin conditions in the area affected by the neuropathy that (in the opinion of the investigator) could alter sensation. · Amputations other than toes. · Administration of any investigational drug and/or agent within 30 days prior to screening. · Use of prohibited medications, in the absence of appropriate washout phases. · Abuse of drugs or alcohol within the last 2 years. · Any serious or unstable medical conditions that, in the opinion of the investigator, would compromise participation in the trial. · Any history of, or current, significant psychiatric disorder e.g. any DSM-IV Axis I or II Disorder or patients judged clinically to be a serious suicidal risk. · History of recurrent syncope or hypotension (systolic <90mmHg, diastolic <40mmHg). · Postural hypotension (a fall of 20mmHg in systolic BP or 10mmHg in diastolic BP on standing). · History of transient ischemic attack or stroke. · Carotid bruit, unless significant carotid stenosis (e.g. >70%) has been excluded by appropriate investigation. · History of uncontrolled narrow angle glaucoma. · History of a seizure disorder, including acute epilepsy requiring treatment, alcoholic seizures, a family history of seizures or a history of head traumata that resulted in loss of consciouness or concussion. · Previous exposure to reboxetine. · History of urinary retention or prostatic hypertrophy (unless surgically corrected e.g. by TURP). · History of heart failure (NYHA class ≥2), acute myocardial infarction (onset less than previous 3 months), or unstable angina. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability: · Vital signs · Physical examination · 12-lead ECG · Hematology/Biochemistry · Adverse events
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
health related quality of life and pain related medication utilization |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Comparator treatment arm consisting of routine care optimized on an individual basis |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 | 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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |