Efficacy and Safety of the N0750 Compared to Monotherapies in the Treatment of Painful Diabetic Peripheral Neuropathy

Who can take part

• Ability to confirm voluntary participation and agree to all purposes of the trial, by signing and dating the Informed Consent Form (ICF) in two copies
• Subjects of both sexes, aged between 18 and 80 years
• Previous diagnosis of type 1 diabetes mellitus or type 2 diabetes mellitus
• Subjects diagnosed with PDPN for at least 3 months, confirmed by NSS ≥ 5 points and NIS ≥ 3 points
• Subjects who agree to discontinue current PDPN treatment during the washout period
• Subjects willing and able to comply with all study requirements, including completion of study diary and questionnaires

Who cannot take part

• Previous diagnosis of other types of pain not related to PDPN, which at the Investigator's discretion, may confound the assessment of clinical trial endpoints, such as, but not limited to: peripheral vascular disease (ischemic pain); neurological disorders unrelated to diabetic neuropathy (phantom pain due to limb amputation); other painful conditions (e.g., arthritis)
• Subjects with depression undergoing drug treatment or subjects with severe depression
• Subjects with a previous diagnosis of class III or IV heart failure according to the New York Heart Association criteria
• Prior treatment with chemotherapeutic agents that cause neuropathy, such as, but not limited to: platinum compounds (oxaliplatin, cisplatin and carboplatin) and taxanes (docetaxel and paclitaxel)
• Lack of response to prior treatment with pregabalin at doses ≥ 300 mg and/or duloxetine 60 mg
• Use of prohibited medications within 7 days prior to the Screening Visit or change in concomitant drugs within 30 days prior to the Screening Visit
• Use of prohibited concomitant medications that cannot be discontinued during participation in the clinical trial
• Skin changes in the PDPN area that may cause changes in sensitivity or preclude physical assessment, e.g.: plantar ulcer
• Subjects with a history of angioedema
• History of seizures
• Recent (<6 months) myocardial infarction
• History of current alcohol or drug abuse or dependence
• Subjects with any clinically significant condition, including serious psychiatric disorders, which at the Investigator's discretion make the subject unsuitable for trial participation
• History of any malignancy within the past 5 years, except successfully treated non-metastatic basal cell or squamous cell carcinoma of the skin
• Clinically significant cardiac arrhythmias, second- or third-degree heart block, or left bundle branch block on 12-lead electrocardiogram (ECG)
• Subjects with any other clinically significant clinical or laboratory change that, at the opinion Investigator's opinion make the subject unsuitable for trial participation
• Glycated hemoglobin ≥ 10.5%
• Subjects with severe renal impairment (estimated glomerular filtration rate based on creatinine by the CKD-EPI equation < 30 mL/min) and/or with severe liver disease (Aspartate Aminotransferase and Alanine Aminotransferase twice the reference value)
• Painful peripheral neuropathy due to other causes, e.g. B12 and/or folate deficiency and hypothyroidism
• Patients with increased intraocular pressure or who are at risk of closed-angle glaucoma
• Subjects at risk of suicide at the Investigator's discretion
• Subjects who have participated in other clinical trials in the last 12 months, unless the investigator believes there may be a direct benefit to them
• Pregnant or breastfeeding female subjects or women of childbearing potential who do not agree to use contraception during the clinical trial