Pharmacogenetic Clinical Trial of Nepicastat for Post Traumatic Stress Disorder (PTSD)

Study Overview
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Brief Summary
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Assess the effect of nepicastat in the treatment of in Post Traumatic Stress Disorder (PTSD) in conflict or combat zone experienced veterans, in comparison to placebo.

Detailed Description
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The primary treatment objective is to assess the global efficacy of nepicastat in the treatment of hyper-arousal in Post Traumatic Stress Disorder (PTSD) in conflict or combat zone experienced veterans, in comparison to placebo. The secondary treatment objectives are to assess the ability of nepicastat to induce PTSD remission; treat PTSD and other PTSD symptom clusters and improve quality of life and overall functioning. A medical safety objective is to assess the tolerability and side effects of nepicastat in the treatment of PTSD in veterans who served in conflict zones at least one time between 1990 -2008 [includes Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF), Afghanistan, Gulf War, etc . This is a 6-week study with the long-term objective is to define the best approach to treating PTSD and enhancing the quality of life in patients. Results from this pilot study will assist clinicians in treating active military service members or veterans with PTSD by developing new treatment algorithms for future larger studies.

Official Title
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Pharmacogenetic Clinical Trial of Nepicastat for PTSD

Conditions
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Post Traumatic Stress Disorder (PTSD)

Intervention / Treatment
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* Drug: SYN117 (nepicastat)
* Drug: Placebo comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Patient understands the risks and benefits and agrees to visit frequency and procedures Male or female Any race or ethnic origin Served in conflict zones at least one time between 1990 -2008 [includes Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF), Afghanistan, Gulf War, etc] Currently Active Duty, National Guard, Reservist, Veteran, and/or Retired Military DSM-IV Diagnosis of Post-Traumatic Stress Disorder (PTSD) No substance use disorders (except for nicotine and caffeine) in the previous 2 months Free of psychotropic medication for 2 weeks prior to randomization (a low dose sedative hypnotic is allowed for severe insomnia if used sparingly) Physical and laboratory panel are within normal limits or not clinically significant Women of childbearing potential must be using medically-approved methods of birth control 18 to 65 years of age Exclusion Criteria: Lifetime history of bipolar I, schizophrenia, schizoaffective or cognitive disorders Actively considering plans of suicide or homicide Psychotic symptoms that in the investigator's opinion impair the patient's ability to give informed consent or make it unsafe for patient to be maintained without a neuroleptic Unstable general medical conditions or a contraindication to the use of nepicastat Intolerable side effects or allergic reaction to nepicastat Women planning to become pregnant or breastfeed during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 (Medication arm - SYN117 aka Nepicastat)<br>Veterans will be receiving the study medication Nepicastat initiated with a 3-day loading phase of 40 mg on day 1, 80 mg on day 2 and 120 mg on day 3 (orally) and be continued at 120 mg once daily; During the 8 weeks (weeks: 7-14) extension phase, those from both treatment groups of the RCT phase will start open-label, active Nepicastat (i.e. no chance of placebo) treatment and be followed for an additional 8 weeks. Those who have a prior defined positive clinical response to the study medication, Nepicastat, will be continued on open label Nepicastat at 120mg once daily, in order to assess further improvement and safety; those who do not have a positive clinical response during the 6 weeks RCT will be offered the addition of the standard first-line PTSD pharmacotherapy, Paroxetine. Paroxetine is an allowed concomitant medication (i.e. rescue medication) and is not considered a research medication or subject of a research question during the 8 weeks extension phase. | Drug: SYN117 (nepicastat)<br>* 120 mg per day<br>* Other names: nepicastat;|
| Placebo Comparator: 2 (Placebo arm)<br>During the 6 weeks ( weeks: 1-6) double- blind, randomized clinical trial (RCT) phase, the veterans who have been randomized to the placebo treatment group will be receiving placebo pills. During the 8 weeks (weeks: 7-14) extension phase, all veterans from both treatment groups of the RCT phase will start open-label, active Nepicastat (i.e. no chance of placebo) treatment and be followed by the study team for an additional 8 weeks. The veterans on the placebo during the RCT will receive the study medication at end of the study week 6, the medication will be initiated with a 3-day loading phase of 40 mg on day 1, 80 mg on day 2 and 120 mg on day 3 (orally) and be continued at 120 mg once daily for 8 weeks until the end of the study. | Drug: Placebo comparator<br>* once per day placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in CAPS(D) hyperarousal scores as compared to placebo |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Structured Interview of Posttraumatic Stress Disorder (SIP) as compared to placebo |  | 6 weeeks | 
| Change from baseline in Montgomery Asberg Depression Rating Scale (MADRS)as compared to placebo |  | 6 weeks | 
| Clinicians global impression of Severity and Improvement |  | 6 weeks | 
| Quality of life assessment as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). |  | 6 weeks | 
| Change from baseline in Davidson Trauma Scale (DTS) as compared to placebo |  | 6 weeks | 
| Change from baseline in Sheehan Disability Scale as compared to placebo |  | 6 weeks | 
| Change from baseline in Clinician Administered PTSD Scale- Symptom (CAPS-SX) as compared to placebo |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTSD