Orvepitant (GW823296) in Adult Post Traumatic Stress Disorder

The purpose of the current study is to test the safety and effects of orvepitant, an
investigational drug for the treatment of noncombat-related PTSD.

Efficacy will be assessed using standard symptom and severity rating scales (questionnaires).
The Clinicain Adminstered PTSD Scale (CAPS) will serve as the primary measure of efficacy.
Secondary efficacy endpoints include the CAPS subscale clusters (Re-Experiencing, Avoidance
and Numbing, and Hyperarousal), the Davidson Trauma Scale (DTS), the Short PTSD Rating
Interview (SPRINT), the Hamilton Depression Rating Scale (HAM-D), the Clinical Global
Impression- Global Improvement and Severity of Illness Scale (CGI-I and CGI-S, respectively),
the Cognitive and Physical Functioning Questionnaire (CPFQ) and the Pittsburgh Sleep Quality
Index (PSQI).

Safety and tolerability will be assessed by monitoring adverse events (AEs or side effects),
physical examinations (including vital signs such as blood pressure and heart rate), clinical
laboratory assessments (blood tests), electrical recordings of the heart (electrocardiograms
or ECG's), the Columbia Suicidality Severity Rating Scale (CSSRS), Massachusetts Sexual
Function Questionnaire (MSFQ), Discontinuation-Emergent Signs and Symptoms (DESS) scale and
weight change.

Blood samples will be taken at different time points to assess blood levels of orvepitant in
patients, allowing the relationship between amount of orvepitant in the body and efficacy to
be studied.

The primary objective of the study is to evaluate the efficacy of orvepitant (60mg/day)
versus placebo (a "sugar pill", with no active ingredients). The secondary objectives include
assessing the safety and tolerability of orvepitant, assessing the profile of appearance and
disappearance of orvepitant in the body (blood) following administration (i.e., assessing how
long the drug remains in the body), and lastly to examine the relationship between blood
levels of the drug and efficacy (i..e, the change in CAPS score relative to what it was
before starting the study medication).

Following an initial screening visit, subjects fulfilling the study entrance criteria will
enter a pre-treatment screening phase to permit evaluation of the laboratory and
electrocardiogram assessments and to confirm eligibility for inclusion into the study. This
screening phase will be a minimum of 7 days, but no longer than 21 days. Upon completion of
the screening period, eligible subjects will be randomly assigned at the baseline visit to
one of two treatment regimens: orvepitant 60mg/day or placebo for a 12-week treatment phase.
The chances of receiving each of the two possible treatments will be equal. Orvepitant will
be administered as tablets. Those subjects randomised to receive placebo will receive study
medication identical in appearance to that received by subjects assigned to receive
orvepitant.

During the treatment phase, subjects will be required to return to the clinic at the end of
Weeks 1, 2, 4, 6, 8, 10 and 12. In addition, all subjects will be required to return for a
follow-up visit 14 days after the last dose of study medication. In addition, all subjects
with ongoing adverse events at the 14-day follow-up visit will be required to return for a
further follow-up visit 28 days after the last dose of study medication. Women of
child-bearing potential will also be required to attend the 28-Day follow-up visit for a
pregnancy test. A further test will be performed 42 Days following the end of treatment.

Male and female outpatients between the ages of 18 to 64 years inclusive with a primary
diagnosis of noncombat-related PTSD will be enrolled into this study. A total of
approximately 240 subjects are expected to be enrolled at approximately 25 different study
sites in North America.

Inclusion Criteria:

- Aged 18-64 years, inclusive.

- A primary diagnosis of noncombat-related Post traumatic Stress Disorder (PTSD)

- Subjects with symptom severity considered to be at least moderate to severe.

Exclusion Criteria:

- Subjects whose symptoms are better accounted for by a diagnosis other than Post
traumatic Stress Disorder (PTSD), subjects diagnosed with dementia; subjects diagnosed
with a current/recent eating disorder such as anorexia nervosa or bulimia; subjects
with a diagnosed history of schizophrenia, schizoaffective disorder, or Bipolar
Disorder.

- Subjects who have a history of failing to respond to adequate treatment for PTSD with
an antidepressant/anti-anxiety drug, i..e, failure to improve following administration
of at least two other antidepressants/anti-anxiety drugs, each given for at least 4
weeks.