A Phase 2, Multicenter, Randomized, Double-blind, Placebo Controlled Study for the Pain of Diabetic Peripheral Neuropathy

Primary Objective: To evaluate the efficacy of SKL11197 for the treatment of diabetic peripheral neuropathy pain (DPN).

Secondary Objective: To evaluate the safety and tolerability of SKL11197 in subjects with painful diabetic peripheral neuropathy.

Primary Efficacy Endpoint: The primary efficacy outcome variable will be the time to exit from the double-blind phase because of inadequate pain relief.

This study is a double-blind, placebo controlled study with three phases;

1. a pre-study medication washout/screening phase upto 3 weeks
2. a 3-week, open label phase
3. a 6-week double-blind phase At the end of 3-week in the open label phase, subjects may enter the double-blind phase if they meet the eligibility criteria.

Eligible subjects will be randomized in a blinded fashion either to continue with SKL11197 at 300 mg TID or to take the same number of placebo capsules.

• Drug: SKL11197
  SKL11197 drug product contains 150 mg of active ingredient. Dosing will be three times per day.
• Drug: Placebo
  This is the placebo. Patients will be randomized the placebo.

• Active Comparator: SKL11197
  If the subject meets the eligibility criteria, he/she will be enrolled into the open label phase of the study. At the end of the open label duration of 3 weeks, the subjects will be randomized to either the SKL11197 or placebo arm.
  Intervention: Drug: SKL11197
• Placebo Comparator: Placebo
  This arm is the placebo comparator arm. Patients will be randomized to this arm.
  Intervention: Drug: Placebo

Inclusion Criteria:

1. 18 years or older
2. Diagnosis of Type 1 or Type 2 diabetes mellitus for at least 1 year
3. At least moderate pain, ≥ 40mm on a 100mm VAS at the end of washout phase (in absence of any analgesic);
4. HbA1c < 12 % at Screening
5. Daily pain attributed to diabetic neuropathy for least 3 months prior to Screening on the basis of history and physical examination documenting peripheral neuropathy.
6. Pain from diabetic neuropathy should be identifiable by the subject. Pain must involve the lower extremities and be bilateral.
7. Females must be of non-childbearing potential (defined as either surgically sterile or at least one year postmenopausal, Menopause is defined as 1 year since last menstrual period with associated subjective sensations), or,
8. If capable of bearing children, females must use a double-barrier method of contraception, or an intrauterine device. Females capable of bearing children must have negative serum pregnancy (beta-HCG) test at Screening and negative urine pregnancy on Day 1.

Exclusion Criteria:

1. Pregnant or lactating females
2. Subjects with BMI over 40
3. Pain due to symptomatic peripheral vascular disease (e.g. intermittent claudication)
4. Subjects with known clinically significant decreased blood flow to the extremities
5. Subjects cannot have pain from other sources that can confuse the assessment of the diabetic neuropathic pain
6. Peripheral neuropathy attributable to other causes such as alcoholism, connective tissue disease, or toxic exposure;
7. Have profound autonomic dysfunction, or brittle diabetes;
8. Evidence of amputations (including toes), open ulcers, or Charcot joint.