Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) affects up to 50% of patients who have diabetes for at
least 25 years. Up to 26% of all patients with DPN experience neuropathic pain. DPN pain
contributes to sleep disorders, depression, and anxiety, which together may have an impact on
a patient's well-being and quality of life.

There are currently several drugs used to treat painful DPN. For example, Lyrica®
(pregabalin) is approved by the United States Food and Drug Administration (FDA) to treat
neuropathic pain associated with DPN and is commonly prescribed. The dosage of the
FDA-approved drugs is limited by side-effects such as dizziness, sleepiness, weight gain and
swelling of the hands, legs, and feet. As a result, many patients suffering from DPN pain do
not get satisfactory pain relief.

Inclusion Criteria:

1. Age > 18 years of age

2. Able to give informed consent and willing to comply with scheduled visits, treatment
plan, laboratory tests, and other trial procedures

3. Type 1 or type 2 diabetes with a hemoglobin A1c (HbA1c) ≤ 10% at Screening and on a
stable antidiabetic medication regimen for at least 30 days prior to Screening
(insulin therapy is acceptable)

4. Painful distal symmetrical sensorimotor polyneuropathy (as per American Society of
Pain Educators guidelines ) diagnosed for at least 6 months, based on neurological
history and/or examination; diagnosis includes absent or reduced deep tendon reflexes
at both ankles

5. At Screening, a pain score of ≥ 40 mm on the SF-MPQ VAS

6. At Randomization, a pain score of ≥ 40 mm on the SF-MPQ VAS and an ADPS of ≥ 4 on the
11-point NRS, the latter calculated from a minimum of 4 pain ratings in daily diaries
obtained during the 1-week Baseline Period (prior to randomization)

7. Creatinine clearance > 60 mL/min (estimated using the Cockcroft-Gault equation)

8. Antidiabetic and other medications anticipated to remain stable and constant during
the study period

9. Women of child bearing potential (WOCBP) must be using an adequate method of
contraception as detailed in the protocol to avoid pregnancy during the study and for
4 weeks after study completion

Exclusion Criteria:

1. Diagnosis of mononeuropathy

2. Use of concomitant medications that may confound assessments of efficacy and/or safety
(see Section 5.2)

3. Major psychiatric disorders

4. Have had a malignancy other than basal cell carcinoma within the past 2 years

5. At Visit 1, have a white blood cell count < 2500/mm3, neutrophil count < 1500/mm3, or
platelet count < 100 x 103/mm3

6. Clinically significant unstable diabetes mellitus, unstable hepatic, respiratory, or
hematologic illness, unstable cardiovascular disease (including myocardial infarction
in the 3 months prior to Visit 1), or symptomatic peripheral vascular disease

7. Clinically significant findings on the Screening ECG

8. History of pernicious anemia, untreated hypothyroidism, chronic hepatitis B, hepatitis
B within the past 3 months, or human immunodeficiency virus infection

9. Amputations of body parts other than toes

10. Prior therapeutic failure of pregabalin or gabapentin (considered unresponsive or
intolerant to treatment); therapeutic failure implies lack of efficacy following full
titration to effective doses (eg, 300 mg/day for pregabalin)

11. Known hypersensitivity to pregabalin or gabapentin

12. Requirement for concomitant anticonvulsant and antidepressant therapy, with the
exception of stable doses of SSRIs

13. Neurologic disorders unrelated to DPN that may confound the assessment of pain
associated with DPN

14. Skin conditions that could alter sensation

15. Other sources of pain that may confound assessment or self-evaluation of the pain due
to DPN

16. Abuse of prescription medications, street drugs or alcohol (including alcohol
dependence) within the last 1 year

17. Current enrollment in another investigational study, participation in another
investigational study with the past 30 days, or other current or recent use of any
investigational drug

18. Pregnancy (as based on lab test results) or breast feeding

19. Laboratory values exceeding limits listed in Table 4.1 of the protocol