Orvepitant (GW823296) in Adult Post Traumatic Stress Disorder
Condition: Post-Traumatic Stress Disorder
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a 12-week, randomized, multicenter, double-blind, placebo controlled, fixed-dose
      parallel group study to assess the efficacy and safety of orvepitant (60 mg/day) versus
      placebo in subjects with a diagnosis of noncombat-related Posttraumatic Stress Disorder
      (PTSD), whose symptoms are considered moderate or severe.

      Following an initial screening visit, subjects fulfilling the study inclusion and exclusion
      criteria will enter a pre-treatment screening phase to permit evaluation of the laboratory
      and ECG 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. At the completion of the
      screening period, eligible subjects will be randomized at the baseline visit to receive
      either orvepitant 60mg/day or placebo (1:1 ratio). Those subjects randomized to receive
      placebo will receive study medication identical in appearance to that received by subjects
      assigned to receive orvepitant.

      Efficacy will be assessed using the Clinician Administered PTSD Scale (CAPS) as the primary
      efficacy measure. Key secondary efficacy endpoints will be based on the Davidson Trauma Scale
      (DTS), the Short PTSD Rating Interview (SPRINT), the Clinical Global Impression- Global
      Improvement and Severity of Illness Scales (CGI-I and CGI-S, respectively), the Hamilton
      Depression Rating Scale (HAM-D), the Cognitive and Physical Functioning Questionnaire (CPFQ)
      and the Pittsburgh Sleep Quality Index (PSQI).

      Safety will be assessed by monitoring for adverse events (side effects) and through periodic
      laboratory evaluations (blood tests), vital signs assessments (e.g., blood pressure, heart
      rate, temperature) and heart function measurements (electrocardiograms, or ECGs).
    

Detailed description: 
      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.
    

Intervention name(s): orvepitant; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Neurokinin-1 (NK-1) antagonist; Inactive placebo to match orvepitant 60 mg dosage form
Other intervention name(s): GW823296
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: efficacy; double-blind; Clinician Administered PTSD Scale; placebo; Sleep; safety; CAPS; neurokinin-1 antagonist; orvepitant; PTSD; randomized; Post traumatic stress disorder; Phase II