A Study in Painful Diabetic Neuropathy

Use of Duloxetine or Pregabalin in Monotherapy Versus Combination Therapy of Both Drugs in Patients With Painful Diabetic Neuropathy "The COMBO - DN (COmbination vs Monotherapy of pregaBalin and dulOxetine in Diabetic Neuropathy) Study"

This study will investigate the efficacy of a combination treatment of duloxetine + pregabalin compared with the maximal dose of each drug in monotherapy, in patients with diabetic peripheral neuropathic pain (DPNP) who have not responded to the standard recommended dose of either drug. It will provide an answer to a common clinical question, namely, is it better to increase the dose of the current monotherapy or to combine both treatments early on, in patients who do not respond to standard doses of duloxetine or pregabalin.

Inclusion Criteria:

• Pain due to bilateral peripheral neuropathy (caused by type 1 or type 2 diabetes mellitus. Pain must begin in the feet, with relatively symmetrical onset. Daily pain should be present for more than 3 months [assessed by questioning patient]).
• Score of at least 4 on the 24-hour average pain severity score on an 11-point Likert scale [on Brief Pain Inventory (BPI) Modified Short Form] at screening and at randomization.
• Patient is currently not receiving treatment for diabetic peripheral neuropathic pain (DPNP) or was receiving treatment for DPNP, with a drug other than pregabalin or duloxetine, and completed the required washout
• Patient has never received treatment with duloxetine or pregabalin. (However, a short course of less than 15 days of treatment, at any time previously, will be allowed.)
• Stable glycemic control, as assessed by a physician investigator, and hemoglobin A1c (HbA1c) less than or equal to 12% at screening.

Exclusion Criteria:

• Have a known hypersensitivity to duloxetine or pregabalin or any of the inactive ingredients or have any contraindication for the use of duloxetine or pregabalin.
• Have uncontrolled narrow-angle glaucoma.
• Have received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to randomization, or have a potential need to use a MAOI during the study or within 5 days after discontinuation of study drug.
• Have received fluoxetine within 30 days prior to randomization.
• Have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
• Have a serum creatinine greater than or equal to 1.5 milligram per deciliter (mg/dL) or a creatinine clearance less than 60 milliliter per minute (mL/min), at screening.
• Are judged clinically by the investigator to be at suicidal risk or as defined by a score of 2 or greater on Question 9 of the Beck Depression Inventory-II (BDI-II), at screening or randomization
• Have a historical exposure to drugs known to cause neuropathy (for example, vincristine), or a history of a medical condition, including pernicious anemia and hypothyroidism, that could have been responsible for neuropathy.
• Have pain that cannot be clearly differentiated from or conditions that interfere with the assessment of the DPNP.
• Have serious or unstable cardiovascular, hepatic, renal, respiratory or hematological illness; symptomatic peripheral vascular disease; a history of seizure disorder; or other medical (including unstable hypertension and not clinically euthyroid) or psychological conditions that, in the opinion of the investigator, would compromise participation or be likely to require hospitalization during the course of the study.
• Have received non-pharmacological treatment for pain within 14 days prior to randomization, or do not agree to abstain from non-pharmacological treatment during the study.
• Have a history of frequent and/or severe allergic reactions with multiple medications.