Trazodone/Gabapentin Fixed Dose Combination Products in Painful Diabetic Neuropathy

Exclusion Criteria

• •1. Known hypersensitivity to trazodone or gabapentin or any excipients of the test drugs.
• •2. Any other form of non-diabetic distal symmetric polyneuropathy or any other pain condition that can impair the study endpoint (e.g. painful conditions where the intensity of pain is significantly more severe than the diabetic peripheral neuropathic pain).
• •3. Concomitant treatment with medications for pain management that could not be discontinued.
• •4. Concomitant treatment with potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, indinavir) or drugs known to prolong QT interval.
• •5. Use of trazodone or gabapentin in the previous 3 months.
• •6. Known history of previous non-responder to gabapentin treatment.
• •7. Use of high dose morphine (e.g. \> 120 mg/day) at the Screening Visit.
• •8. Clinically significant abnormalities on physical examination, vital signs, elettrocardiogram, laboratory tests at Screening Visit that in the opinion of Investigator would compromise patient's participation in the study.
• •9. Active foot ulcer or previous major limb amputation.
• •10. Concurrent heart failure ≥ 4 class according to New York Heart Association (NYHA) or myocardial infarction or angioplasty or by-pass graft procedures within the past 6 months.
• •11. Patient with increased risk of Torsade de Pointes (e.g. family history of long QT syndrome) or QTcF value higher than 450 msec (male) and QTcF value higher than 470 msec (female) at Screening Visit.
• •12. Transient ischemic attack or cerebral vascular accident within the past 6 months.
• •13. Glomerular Filtration Rate value \< 50 ml/min calculated with Modification of Diet in Renal Disease formula.
• •14. Significant liver disease, defined as known active hepatitis or elevated liver enzymes over 3-fold the upper normal limit of laboratory normal ranges.
• •15. Patient with latent or known hereditary problems of galactose intolerance or the Lapp lactase deficiency or glucose-galactose malabsorption.
• •16. Positive urine drug screen for Central Nervous System active drugs (cocaine, opioids, amphetamines and cannabinoids) at Screening Visit.
• •17. Positive present history of glaucoma.
• •18. Hyperthyroidism, even if pharmacologically corrected.
• •19. Significant mental disorders.
• •20. Suicide risk score ≥ 2 on question 9 of the Beck Depression Inventory-II (BDI-II) at Screening visit or Visit 0.
• •21. History of epilepsy or seizure events other than a single childhood febrile seizure.
• •22. History of alcohol or psychoactive substance abuse or addiction.
• •23. Use of neurological device (e.g. neurostimulation devices, etc).
• •24. Women during pregnancy or lactation period.
• •25. Inability to comply with the protocol requirements, instructions or study-related restrictions (e.g. uncooperative attitude, inability to return for study visits, improbability of completing the clinical study, etc).
• •26. Subject involved in the conduct of the study (e.g. Investigator or his/her deputy, first grade relatives, pharmacist, assistant or other personnel, etc).
• •27. Participation to an interventional clinical trial within 3 months prior to Screening Visit.