Study to Evaluate the Safety and Analgesic Activity of ATx08-001 in Subjects With Postherpetic Neuralgia

Aestus has identified a novel selective peroxisome proliferator-activated receptor modulator
(SPPARM), with promising potential for the treatment of neuropathic pain. PPARs are nuclear
receptors that control many cellular and metabolic processes and are readily modulated by a
variety of different drugs. Drugs modulating this target have been shown to improve blood
glucose levels and levels of blood lipids, and may reduce the risk of atherosclerosis.

The primary objective of the study is to evaluate the safety and analgesic efficacy of
ATx08-001 at doses of 2.5 mg bid and 7.5 mg bid compared to placebo for the control of
moderate-to-severe postherpetic neuralgia (PHN) pain.

The secondary objectives are:

- To determine the approximate time to onset of analgesia following administration of
study drug

- To determine the approximate duration of analgesia following study drug administration

- To determine the percentage of treatment responders among subjects receiving ATx08-001

Subjects will be given a diary and instructed to record their postherpetic neuralgia pain
severity on a Numerical Pain Rating Scale (NPRS - 12) "over the past 12 hours" on a 0 - 10
scale with "0" being no pain and "10" being the most severe pain the subject could imagine,
each morning and night for three consecutive days prior to returning for the Treatment Visit.

The Treatment Visit will consist of an in-clinic 6-hour observation period. To be eligible
for dosing, immediately before dosing subjects must report a baseline score of 4 or greater
on the following Numerical Pain Rating Scale (NPRS-NOW) question: "How would you rate your
pain RIGHT NOW using a zero to ten scale, where zero equals no pain and ten is the worst pain
you can imagine." Qualified subjects will be administered study drug followed by a 6-hour
observation in-clinic period. In addition to the Baseline pain intensity assessment conducted
just prior to drug administration (Time 0), pain intensity scores (pain right now) will be
assessed using the NPRS-NOW at 30 minutes, 1, 2, 3, 4, and 6 hours following study drug
administration. Pain relief compared with Baseline will be assessed at those same time points
using a 5-point numerical pain relief (NPR) scale, where 0 = no relief, 1 = a little relief,
2 = some relief, 3 = a lot of relief, and 4 = complete relief.

Subjects will be discharged from the clinic at the end of the 6-hour observation period and
will be instructed to record postherpetic neuralgia pain severity (NPRS-NOW scores) and pain
relief (PAR scores) at 8, 10 and 12 hours following dosing in a diary.

Inclusion Criteria:

- Is able to provide written informed consent prior to study entry

- Is male or female, 18 - 85 years of age

- Has a diagnosis of postherpetic neuralgia that has been present for at least 3 months
since the resolution of the skin rash (shingles), and has been associated with at
least moderate pain

- Has a body mass index (BMI) between 17 and 36, inclusive

- Has on average postherpetic neuralgia pain severity of at least "4" on the 11-point
NPRS-12 scale over three days prior to the Treatment Visit.

- At the Treatment Visit, entry into the study for dosing will require a baseline score
of 4 or greater on the following 'Numerical Pain Rating Scale' (NPRS-NOW): "How would
you rate your pain RIGHT NOW using a zero to ten scale, where zero equals no pain and
ten is the worst pain you can imagine." If the subject fails to qualify for the
Treatment Visit because of a baseline pain score below 4, he or she may return on any
day within a fourteen day period to attempt to qualify again. A subject will be
allowed a maximum of two reassessments to qualify on the basis of the NPRS-NOW scale.

- Female subjects must be of non childbearing potential (defined as postmenopausal for
at least 1 year or surgically sterile [bilateral tubal ligation, bilateral
oophorectomy or hysterectomy]) or must be using adequate contraception (practicing one
of the following methods of birth control):

- Total abstinence from sexual intercourse (minimum of one complete menstrual cycle
before study entry),

- A partner who is physically unable to impregnate the subject (e.g., vasectomized)

- Contraceptives (oral, parenteral, or transdermal) for 3 consecutive months prior to
study drug administration,

- Intrauterine device (IUD), or

- Double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal
jellies or cream)

- If female of childbearing potential, subject must have a negative serum pregnancy test
at screening

- Able to communicate meaningfully with the study observer and staff

- No known allergies to study medication

Exclusion Criteria:

- Has another source of moderate-to-severe pain apart from the postherpetic neuralgia
that might be confused with the PHN pain

- Is actively abusing alcohol or drugs

- Is unable to refrain from alcohol for a period beginning 24 hours prior to the
treatment visit until the end of the study

- Is scheduled to undergo any surgical procedures during the period of study duration

- Has a history of any active serious medical conditions including cancer (with the
exception of benign uterine dysplasia or removed skin carcinomas), cardiovascular,
respiratory, renal, hepatic, gastrointestinal, endocrine, immunologic, hematologic,
neurologic or psychiatric disease that would contraindicate study participation

- Has moderate to severe (New York Heart Association [NYHA] Class 3 or 4) heart failure
defined as heart failure which significantly limits physical activity by provoking
fatigue, palpitations or dyspnea.

- Has a history of either type 1 or type 2 diabetes mellitus

- Has taken a fixed scheduled opioid regimen within 3 days prior to the Treatment Visit.
A fixed scheduled regimen of another type of analgesic, e.g., nonsteroidal
antiinflammatory drug (NSAID) or an adjuvant analgesic will be allowed as long as the
dose and schedule of administration were not changed for at least 2 weeks prior to
dosing.

- Has used a short-acting "as needed" opioid less than 12 hours prior to dosing or an
"as needed" NSAID dose less than 24 hours prior to dosing

- Has used extended duration oral analgesics up to 48 hours prior to the Treatment Visit

- Has applied lidocaine patches or dermal analgesics within 7 days prior to the
Treatment Visit

- Has received an anesthetic block within two weeks of the Screening Visit

- Has received any prior neurolytic nerve block in the area of the PHN pain

- Is taking tricyclic, selective serotonin reuptake inhibitor (SSRI) or serotonin and
noradrenaline reuptake inhibitor (SNRI) antidepressants for PHN (or for indications
other than pain) and the dosage has been changed within 14 days of the Treatment
Visit. Only subjects on stable doses from at least 14 days prior to the Treatment
Visit through the duration of the study will be eligible to participate

- Is taking gabapentin (Neurontin), pregabalin (Lyrica), or duloxetine (Cymbalta) and
the dosage has been changed within 14 days of the Treatment Visit. Only subjects
receiving stable doses for at least 14 days prior to the Treatment Visit and are
willing to continue taking the same doses for the duration of the study will be
eligible to participate

- Has taken any medication that is a substrate of the cytochrome P450 enzyme CYP2C9
within 4 days of dosing with study drug or is unwilling to refrain from such
medications through the course of study drug treatment

- Has taken any prescription or over-the-counter medication within three days prior to
the Treatment Visit, or herbal agents or other nutraceutical products within 14 days
prior to the Treatment Visit, that in the opinion of the Investigator would be
expected to confound the analgesic response

- Has documented liver failure or a serum ALT, AST, alkaline phosphatase, or GGT greater
than 2.5 times the upper limit of normal, or total bilirubin greater than 1.5 times
the upper limit of normal without a known, not clinically significant explanation

- Has a Brain Natriuretic Peptide (BNP) level > 150 pg/mL

- Has a history of poorly controlled hyperthyroidism or hypothyroidism or Thyroid
Stimulating Hormone (TSH) levels that are < 0.3 or > 5.5 µlU/mL

- Has moderate or severe renal failure defined as a calculated creatinine clearance of <
60mL/min from the Cockcroft & Gault formula

- Has a clinically significant abnormality on 12-lead electrocardiogram

- Has a known history of a positive Human Immunodeficiency Virus (HIV) antibody test or
known HIV infection

- Has a history of a positive Hepatitis B core antibody, or anti-HCV antibody test

- Has previously been admitted to this study

- Has received an investigational medication within 30 days prior to the Treatment Visit