Please select the eligibility criteria that correspond to the clinical trial below.
Title: Study PXN110448: A Dose-response Study of XP13512, Compared With Concurrent Placebo Control and LYRICA(Pregabalin), in Subjects With Neuropathic Pain Associated Withdiabetic Peripheral Neuropathy (DPN)
Brief Summary: The purpose of this study is to determine whether gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn is effective in the treatment of neuropathic pain associated with diabetic peripheral neuropathy(DPN)


Options:
A: Inclusion Criteria:

* Chronic pain below the neck present for a minimum of one year.
* Diagnosis of at least one of the following:

  * back pain with or without leg pain,
  * post-herpetic neuralgia,
  * complex regional pain syndrome (CRPS) 1 or 2,
  * diabetic neuropathy,
  * or a general neuropathic condition; medically stable and able to undergo surgery for implantation of the drug infusion system.
B: Inclusion criteria:

* 18 years or older
* Female subjects are eligible to enter if of non-childbearing potential or not lactating, has a negative pregnancy test and agrees to use a specified highly effective method for avoiding pregnancy
* Documented medical diagnosis of Type 1 or 2 diabetes including:
* Stable glycemic control for 3 months defined as \<25% change of routine insulin, \<50% change of routine oral anti-diabetic agent dose and HbA1c \< 8%. (HbA1c of 8 to 11% eligible if attempts to improve diabetic control failed)
* DPN defined by:
* Bilateral reduced or absent reflexes at the ankles, or
* Bilateral impaired vibration, pinprick, fine touch or temperature perception in the distal lower extremities And
* 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
* history of pain for at least six months and no greater than five years attributed to DPN (refers to duration of pain)
* Baseline 24-hour average daily pain intensity score \>4.0 as measured on an 11 point pain intensity numerical rating scale
* Provides written informed consent in accordance with all applicable regulatory requirements

Exclusion criteria:

* Other chronic pain conditions not associated with DPN. 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 DPN, and
* The subject can assess their DPN independently of other pain condition.
* Other causes of neuropathy or lower extremity pain
* Is unable to discontinue prohibited medications or non-drug therapies or procedures throughout the duration of the study
* Hepatic impairment defined as ALT or AST \> 2x upper limit of normal (ULN) or alkaline phosphatase or bilirubin \> 1.5x ULN
* Chronic hepatitis B or C
* Impaired renal function defined as either creatinine clearance \< 60 mL/min or requiring hemodialysis
* Corrected QT (QTc) interval \>450 msec or QTc interval \>480 msec for patients with Bundle Branch Block
* Uncontrolled hypertension at screen (sitting systolic \>160 mmHg and/or sitting diastolic \>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 GEn or 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
* Meets criteria defined by the DSM-IV-TR for a major depressive episode or for active significant psychiatric disorders within last year
* Depression in remission, with or without antidepressant treatment, may participate, unless stable antidepressant regimen is a prohibited medication
* Antidepressant medication may not be changed or discontinued to met entry criteria and must be stable for at least 3 months prior to enrollment
* History of clinically significant drug or alcohol abuse (DSM-IV-TR). Benzodiazepines or atypical benzodiazepines as hypnotic sleep agents permitted
* 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 and was exposed to investigational or non-investigational drug or device:
* Within preceding month for studies unrelated to DPN, or
* Within six months for studies related to DPN
* Treated previously with GEn
* History of allergic or medically significant adverse reaction to investigational products (including gabapentin or pregabalin) or their excipients, acetaminophen or related compounds
C: Inclusion Criteria:

* You must have been diagnosed with Diabetic Neuropathic Pain
* Patient has an average daily pain score greater than or equal to 4 on an 11-point Likert scale, and patient or provider feel that a change from the current gabapentin therapy for pain management is warranted
* Patient is currently treated with gabapentin greater than or equal to 900 milligram/day, has been prescribed the current dose for at least 4 weeks, and has been at least 80% compliant with dosing, according to patient report
* Patient must agree not to change dose of gabapentin between Visits 1 and 2
* You must have stable glycemic control

Exclusion Criteria:

* Are judged prior to randomization to be at suicidal risk as defined by a score of 2 or greater on question 9 of the Beck Depression Inventory-II (BDI-II)
* Current diagnosis or history of hemangiosarcoma
* Patients with New York Heart Association Class III or IV symptoms of congestive heart failure
* Patients with uncontrolled narrow-angle glaucoma
* Presence of a current seizure disorder
D: Inclusion Criteria:

* Men or women 18 years or older with diagnosis of type 1 or type 2 diabetes who have reported symmetrical painful symptoms in distal extremities for 1-5 years prior to the study and whose symptoms are attributable to sensorimotor diabetic peripheral neuropathy (DPN).
* Patients of childbearing potential must have a negative urine pregnancy test at screening/randomization, and must use medically acceptable methods of birth control.
* Patient has pain score of at least 4 on the 11-point Likert numerical rating scale at screening. Potential patients should not be informed of the pain intensity eligibility criterion prior to screening or randomization.
* Patient has a mean baseline week pain intensity of at least 4 on the 11-point Likert scale at the end of a one-week pre-treatment period and has completed at least 4 days of diary entries during the baseline week.
* Patient is on stable regimen of antidiabetes medication at screening that can be maintained during the study.
* Patient has hemoglobin A1c (HbA1c) ≤11% at screening.
* Patient has FPG ≤310 mg/dL at screening.
* Patient must have a minimum washout of greater than 5 times the half-life of the drug of any of several medications
* Patients currently treated with gabapentin or pregabalin at screening may be eligible for the study, but must have tapering period wherein the dose of gabapentin is reduced gradually over a period of at least 7 days plus a 2-day or 3-day washout of gabapentin or pregabalin, respectively, prior to start of the Baseline Week.
* Patient must have adequate eyesight to complete questions on the DiaryPro and SitePro. If a patient is unable to do so (for reasons other than severe eye disease) but a caregiver is available to complete these tasks following instruction from the patient, the caregiver may be trained to accomplish these tasks

Exclusion Criteria:

* Patients who have previously not responded to treatment for DPN with gabapentin at doses of ≥1200 mg/day or pregabalin at doses ≥300 mg/day.
* Patients who previously experienced dose-limiting adverse effects that prevented titration of gabapentin to an effective dose.
* Patient has hypersensitivity to gabapentin.
* Patient is a nursing mother.
* Patient has used injected anesthetics or steroids within 30 days of baseline.
* Patient has certain conditions that could confound evaluation of painful DPN, in particular, amputations other than toes, non-diabetic neurologic disorders (e.g. phantom limb pain), and skin conditions affecting sensation in painful limbs.
* Patient has skin conditions in the area affected by the neuropathy that could alter sensation.
* Patient is in an immunocompromised state.
* Patient has an estimated creatinine clearance of \<60 ml/min calculated using the Cockroft Gault method (Appendix 3).
* Patient has had malignancy within past 2 years other than basal cell carcinoma.
* Patient has had gastric reduction surgery.
* Patient has severe chronic diarrhea, chronic constipation \[unless attributed to drugs that will be washed out\], uncontrolled irritable bowel syndrome (IBS) or unexplained weight loss.
* Patient has any abnormal chemistry or hematology results that are deemed by the investigator to be clinically significant.
* Patient has a history of substance abuse within the past year.
* Patient has had 1 or more visits to an emergency room or hospital within the previous 30 days due to hypoglycemia.
* Patient has a history of seizure (except for infantile febrile seizure) or is at risk of seizure due to head trauma.
* Patient has a history of pernicious anemia, untreated hypothyroidism, chronic hepatitis B or C, hepatitis within the past 3 months, or HIV infection.
* Patient has any other serious medical condition that, in the opinion of the Investigator would jeopardize the safety of the patient or affect the validity of the study results.
* Continuing use of any concomitant medication excluded by Inclusion Criterion 8.
* Patient has participated in a clinical trial of an investigational drug or device within 30 days of the screening visit

Answer: B