Study of DA-9801 to Treat Diabetic Neuropathy

This is a double-blind, randomized, parallel group, dose ranging, placebo-controlled study where eligible subjects (age 18 to 75 years) will have an average pain score ≥ 4 on an 11-point Likert numerical rating scale (NRS) for at least four days each week prior to randomization as assessed by daily pain diaries. Eligible subjects will be randomized to a 1:1:1:1 ratio to receive 300mg, 600mg, 900mg of DA-9801, or placebo three times a day for 12 weeks. During and at the end of the 12-week treatment period subjects will be evaluated for safety and efficacy parameters. A follow-up visit for safety will occur two weeks after the last treatment visit (TV).

The Screening Phase (2 weeks) is designed to determine whether subjects are eligible to proceed to the Treatment Phase of the study and consists of a series of screening assessments designed to determine eligibility. Eligible subjects will undergo a two-week washout period for medications and therapies administered for pain management.

At or up to 21 days before the Screening Visit, written informed consent from (ICF) the subject will be obtained by the Investigator or a suitably qualified designee before the performance of any protocol specific procedure. At the Screening Visit, the subject will be issued a daily diary in order to record daily pain level during the screening phase.

The Treatment Phase (TV0 to TV12) begins with a series of assessments designed to confirm the subjects' continued eligibility. The site will collect the daily diary and the subject's pain score will be determined. Only subjects whose average pain score is ≥ 4 for at least four days each week will be randomized to any of the four treatment groups.

DA-9801 administration schedule is three times per day, starting from TV0 to TV12.

During this study phase subjects will be evaluated on a weekly basis. Efficacy evaluations each week will include the subject's global impression of improvement and CGI of pain. Safety evaluations during the Treatment Phase will consist of adverse event assessments at each visit.

The Follow-up Visit (two weeks after last TV) The Follow-up Visit is designed to assess safety and will occur 14 days after the last TV. If the subject is withdrawn from the study prior to TV12, the subject should be exited from the study AFTER completing the specified assessments for that visit.

Inclusion criteria

• Must be 18 to 75 years of age
• Diagnosed with Type I or Type II diabetes
• HbA1c ≤ 12% at the time of screening
• Has diabetic neuropathic pain (numbness, soreness, shooting or poking pain) in the lower extremities for more than 3 months prior to screening and with no adequate relief from other treatments
• Has an average pain score of ≥ 4 for 24 hours at least 4 days out of the week prior to randomization as assessed by the 11-point Likert NRS.
• If female of childbearing potential, subject must have a negative serum pregnancy test at screening
• Understands and is willing to participate in the clinical study and can comply with study procedures and visits.
• Normal cognitive and communicative ability as judged by clinical assessment and ability to complete self-reported questionnaires
• Subject is willing and able to give informed consent

Exclusion criteria

• Evidence of another type of neuropathic pain caused by a condition other than diabetes
• Pain from another source as severe or greater than the pain under study
• BMI (Body Mass Index) > 37 kg/m2
• Clinical signs of infection related to sores of any type on the legs
• Subjects on any investigational drug(s) or therapeutic device(s) within 30 days preceding screening; or subject or physician anticipates use of any of these therapies by the subject during the course of the study
• Previous participation in the Treatment Phase of this Protocol
• History of drug or alcohol abuse, within the past 6 months
• Malignant disease not in remission for 5 years or more that has been medically or surgically treated without evidence of metastases
• Presence of one or more medical conditions, as determined by medical history, which seriously compromises the subject's ability to complete the study, including history of poor adherence with medical treatment, renal, hepatic, hematologic, active auto-immune or immune diseases that, in the opinion of the Investigator, would make the subject an inappropriate candidate for this study: c) One or more abnormal blood biochemistry analyte result that is ≥ 3 times that of the upper limit of the normal range; d) For laboratory results that are significantly lower than the normal range, specific criteria will be used to judge subject eligibility for randomization for Total protein, Albumin, and Hemoglobin or Platelets.
• Known history of having Acquired Immunodeficiency Syndrome (AIDS) or with a history known to be infected with Human Immunodeficiency Virus (HIV)
• New York Heart Association (NYHA) Class III and IV congestive heart failure (CHF), as defined by the following criteria: a)Class III: Symptoms with moderate exertion b)Class IV: Symptoms at rest
• Pregnant or breast feeding
• Women of child-bearing potential not using an effective birth control method. Women of child-bearing potential are defined as women physiologically capable of becoming pregnant, UNLESS they meet the following criteria:

d) Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40mIU/m, OR; e) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy, OR; f) Are using one or more of the following acceptable methods of contraception: surgical sterilization, hormonal contraception, and double-barrier methods. Reliable contraception should be maintained throughout the study and for 7 days after study discontinuation.

• Subjects with a diagnosis of psychiatric disorders such as major depressive disorder, bipolar disorder, obsessive compulsive disorder, generalized anxiety, dysthymia or suicidality/suicide ideation
• Administration of local anesthetic shot or systemic steroids within two months of screening
• Subjects not willing to undergo a two-week washout period for pharmacologic and non-pharmacologic pain management techniques