Inclusion criteria:

Prior to randomization, subjects eligible for enrollment in the study must meet all of the following criteria:

• Outpatient subjects aged 18 years or older.
• A female subject is eligible to enter and participate in the study if she:
• Is of non-childbearing potential or
• Is of child-bearing potential, is not lactating and has a negative pregnancy test ≤7 days prior to study treatment initiation and agrees to use one of the GlaxoSmithKline (GSK) specified highly effective methods for avoiding pregnancy.
• A documented medical diagnosis of Type 1 or Type 2 diabetes mellitus including:
• Stable glycemic control for three months prior to randomization (diabetic regimens may be changed after randomization to maintain glycemic control) as defined:
• Insulin: <25% change of their routine insulin dose to maintain glycemic Control
• Oral antidiabetic agents: <50% change of their routine oral dose to maintain glycemic control.

and

• A glycosylated hemoglobin (HbA1c) concentration < 8% at the time of randomization. Subjects with HbA1c concentration of 8 to 11% maybe eligible if, in the opinion of the investigator, attempts have been made by the subject to improve diabetic control but these attempts have failed.

Note: Subjects who achieve stable glycemic control and meet HbA1c criteria through diet control are eligible.

• Distal symmetric chronic sensorimotor painful polyneuropathy (also known as DPN) as defined by:
• Signs including:
• Bilateral reduced or absent reflexes at the ankles, or
• Bilateral impaired vibration, pinprick, fine touch or temperature perception in the distal lower extremities.

and

• Symptoms including:
• Persistent distal burning or dull pain in the feet, or
• Persistent proximal aching pain in the legs, or
• Paroxysmal electric, shooting, stabbing pain, or
• Dysasthesias, or
• Evoked pain. and
• A history of pain for at least six months and no greater than five years attributed to DPN (Note this requirement refers to duration of pain, not the duration of polyneuropathy).
• A baseline 24-hour average daily pain intensity score >4.0 as measured on an 11 point pain intensity numerical rating scale (PI-NRS). The Baseline score is the calculated mean of the daily scores during the 7 days prior to randomization. (The subject must record at least four assessments of the 24-hour average daily pain intensity score during the seven-day Baseline Period).
• The subject must be able to provide written informed consent prior to participation in the study. The contents and process of obtaining informed consent will be in accordance with all applicable regulatory requirements.

Exclusion criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

• Other chronic pain conditions not associated with distal symmetric chronic sensorimotor painful polyneuropathy. However, the subject will not be excluded if:
• The pain condition is located at a different region of the body, and
• The pain intensity of this condition is not greater than the pain intensity of the distal symmetric chronic sensorimotor painful polyneuropathy, and
• The subject can assess their DPN independently of their other pain condition.
• Other causes of neuropathy or lower extremity pain which may include, but not be limited to:
• Lower extremity pain of any severity caused by: mononeuropathy, osteoarthritis of the ankle or foot, gout, bursitis, or fasciitis.
• Diffuse peripheral neuropathy caused by: alcoholism, malignancy, human immunodeficiency virus (HIV), syphilis, drug abuse, peripheral ischemia, B-12 deficiency, hypothyroidism, liver disease, chemotherapy or radiation therapy.
• Focal neuropathy in the lower extremities including nerve entrapment or local trauma.
• Acute or chronic inflammatory polyradiculopathy.
• Focal or multifocal diabetic neuropathies including:
• Mononeuropathies of the cranial nerve, trunk and limb, or
• Entrapment or asymmetric lower limb motor neuropathy (amyotrophy).
• Multiple sclerosis or other conditions associated with central neuropathic pain.
• Pain associated with distal limb ischemia including intermittent claudication. However subjects will not be excluded if amyotrophic pain has resolved more than one year prior to enrolment. The current pain should be due to distal symmetric chronic sensorimotor painful polyneuropathy.
• Is unable to discontinue:
• Prohibited medications or;
• Non-drug therapies or procedures (i.e. nerve blocks, trans cutaneous electrical nerve stimulation [TENS]) for the relief of pain of DPN for the required washout period and throughout the duration of the study.
• Has any of the following medical conditions, laboratory abnormalities or disorders:
• Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x upper limit of normal (ULN) or alkaline phosphatase or bilirubin > 1.5x ULN.
• Chronic hepatitis B or C with a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C Core Antigen Antibody (Hep C antibody).
• Impaired renal function defined as either creatinine clearance < 60 mL/min (estimation of creatinine clearance by Cockroft and Gault Method) or renal dysfunction requiring hemodialysis.
• Corrected QT (QTc) interval >450 msec (based on single or average QTc value of triplicate electrocardiograms (ECGs) obtained over a brief recording period).
• QTc interval >480 msec for patients with Bundle Branch Block.
• Uncontrolled hypertension at screen (sitting systolic blood pressure [SBP] >160 mmHg and/or sitting diastolic blood pressure [DBP] >90 mmHg.
• Current diagnosis of active epilepsy or any active seizure disorder requiring chronic therapy with antiepileptic drug(s).
• Medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of XP13512 or Lyrica (pregabalin), or, in the investigator's judgment:
• Is considered to be clinically significant and could pose a safety concern or,
• Could interfere with the accurate assessment of safety or efficacy, or,
• Could potentially affect a subject's safety or study outcome.

Examples of such medical conditions include:

• Skin conditions at the site of neuropathy.
• Lower extremity amputations other than toes.
• Active infection at the site of the neuropathy.
• Symptomatic peripheral vascular disease.
• Current or chronic history of liver disease (including acute viral hepatitis), or know hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Meets criteria as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM‑IV‑TR) for a major depressive episode or for active significant psychiatric disorders within last year, including dementia, general anxiety disorder, psychosis or bipolar disorder.
• Subjects with a history of depression that is in remission, with or without antidepressant treatment, may participate, unless a stable antidepressant regimen includes a prohibited medication.
• Antidepressant medication may not be changed or discontinued to met entry criteria and must be stable for at least three months prior to baseline.
• Has a history of clinically significant drug or alcohol abuse as defined by DSM‑IV‑TR. Benzodiazepines or atypical benzodiazepines prescribed as hypnotic sleep agents are permitted.
• Is currently participating in another clinical study in which the subject is, or will be exposed to an investigational or non-investigational drug or device.
• Has participated in a clinical study in which the subject was exposed to an investigational or non-investigational drug or device:
• Within the preceding month for studies unrelated to the current illness, or;
• Within the preceding six months for studies related to the current illness.
• Has been treated previously with XP13512.
• Has a history of an allergic reaction, or a medically significant adverse reaction to:
• The investigational products (including gabapentin or pregabalin) or,
• Their excipients, or,
• Acetaminophen, or,
• Compounds closely related to acetaminophen.