Safety, Tolerability and Preliminary Efficacy of AZD5213 in Combination With Pregabalin in Subjects With PDN and Good Pain Reporting Ability

This is a multi-center, randomized, two-part study in adults (ages 18-75 years) with
Painful Diabetic Neuropathy (PDN).

In Part 1 of the study, eligible subjects will enter a 4-week Pain Training Period. During
the Pain Training Period, subjects will receive three weekly in-clinic training sessions
using repeated rating of experimental pressure pain stimuli. Subjects will receive feedback
during this training and will be evaluated on their pain-reporting ability during each
in-clinic session. Subjects with acceptable pain-reporting ability at the conclusion of the
Pain Training Period will be eligible to enter Part 2 of the study. Subjects with
unacceptable pain-reporting ability at the conclusion of the Pain Training Period will be
discontinued from the study.

Part 2 of the study will consist of three consecutive double-blind crossover periods. Each
crossover period will include 31 days of double-blind treatment. A follow-up visit will
occur 14 ± 7 days after the last dose of study medication.

One of three treatments (placebo, pregabalin, or pregabalin + AZD5213) will be administered
during each crossover treatment period, as determined by a randomly assigned treatment
sequence.

Approximately 65 subjects will be screened in Part 1 of the study, in order to randomize up
to approximately 32 subjects in Part 2 of the study.

Inclusion Criteria:

1. Male or female, age 18 to 75 years, inclusive, at Screen. 2. Subjects must provide
informed consent in accordance with local regulations before the conduct of any
study-related procedures. The informed consent should reflect the protocol stipulations
concerning the use of contraception. 3. Diagnosis of Type 1 or Type 2 diabetes mellitus
for at least 1 year prior to Screen. 4. Diabetes-related painful neuropathy for at least
6 months prior to Screen. 5. Pain that began in the feet and is symmetric or nearly
symmetric. 6. Diabetes has been clinically stable for at least 2 months prior to Screen,
and between Screen and baseline (Day 35). 7. At Screen and baseline, score of at least 4
on Item 5 ("average pain") of the modified Brief Pain Inventory for patients with painful
diabetic peripheral neuropathy (BPI-DPN). 8. Able to participate in all scheduled
evaluations and to complete all required tests and procedures. 9. In the opinion of the
investigator, the subject must be considered likely to comply with the study protocol and
to have a high probability of completing the study.

Exclusion Criteria:

1. Known or suspected hypersensitivity to pregabalin. 2. Clinically important illness or
infection (e.g., chronic, persistent, or acute infection) within 30 days prior to screen
or between screen adn baseline. 3. Presence of any psychiatric or neurologic disorder or
any other disorder or symptom, if, in the judgement of the investigator, the disorder or
symptom is likely to confound interpretation of drug effect or affect the subject's
ability to complete the study. Any clinically important abnormality, as determined by
investigator at Screen or baseline, in physical or neurologic examination, vital sign,
ECG, or clinical laboratory test results that could be detrimental to the subject, or
could affect the subject's ability to complete the study. 4. Initiation or change in
intensity or frequency of non-pharmacologic therapy for PDN, including psychotherapy,
physical therapy, massage, acupuncture, acupressure, or chiropractic care, within 3 months
prior to baseline).