Evaluation of GSK561679 in Women With Post-Traumatic Stress Disorder
Condition: Stress Disorders, Post-Traumatic
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: GSK561679; Placebo
Intervention description: GSK561679, oral administration, 350mg/day, 6 week administration; Matching placebo, oral administration, 1 pill/day for 6 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 267.0
Sex: Female
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: PTSD; Anxiety Disorder; Corticotropin releasing factor; Women

Summary:

      This study will test the hypothesis of whether an antagonist at the corticotropin releasing
      factor type 1 (CRF1) receptor (i.e. GSK561679) is superior to placebo in reducing symptoms of
      post-traumatic stress disorder (PTSD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female between 21-65 years of age

          -  Able to provide consent and willing to participate in research

          -  Fulfills Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)
             criteria for primary diagnosis of PTSD

          -  PTSD duration of illness at least 3 months

          -  Able to provide consent and willing to participate in research

          -  CAPS score of ≥ 50 at Screening and Visit 3 (randomization)

          -  Negative Urine toxicology test

          -  Agrees to use protocol-defined effective birth control method

          -  If the patient has a history of peptic ulcer disease (PUD), there is documentation of
             the etiology of the PUD and that effective treatment was provided with full
             eradication of ulcers and symptoms

        Exclusion Criteria:

          -  Lifetime or current diagnosis of schizophrenia or other psychotic disorder, bipolar
             disorder, obsessive compulsive disorder (OCD), or current Axis I disorder [(except for
             major depression secondary to the PTSD, dysthymia, depression not otherwise specified
             (NOS) and anxiety disorders (panic disorder, social phobia, generalized anxiety
             disorder (GAD), specific phobia)]

          -  Subject is currently participating in another clinical trial in which she is or will
             be exposed to an investigational or non-investigational drug or device, or has done so
             within the preceding month for studies unrelated to PTSD, or 1 month for studies
             related to PTSD

          -  Current evidence or history of significant unstable medical illness or organic brain
             impairment, including stroke, central nervous system (CNS) tumor, demyelinating
             disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment that would
             likely interfere with the action, absorption, distribution, metabolism, or excretion
             of GSK561679.

          -  Patients who in the investigator's judgment pose a current suicidal or homicidal risk

          -  DSM-IV substance abuse or dependence within the past 90 days. Subject has a positive
             test for illegal substances.

          -  Diagnosis of anorexia nervosa or bulimia in the past year.

          -  Subject has a documented history of hepato-biliary disease including a history of, or
             positive laboratory results for hepatitis (hepatitis B surface antigen and/or
             hepatitis C antibody), and/or clinically significant hepatic enzyme elevation
             including any one of the following enzymes greater than 1.5 times the upper limit of
             normal (ULN) value (alanine transaminase (ALT), aspartate aminotransferase (AST),
             alkaline phosphatase (ALP), total or direct bilirubin > 1.5 x ULN, unless consistent
             with presumed or diagnosed Gilbert's disease)

          -  Subject has taken systemic corticosteroids within 2 weeks of the Randomization Visit

          -  Treatment with any other psychoactive medication within 2 weeks of Visit 1, including
             all antidepressants, psychoactive herbal or nutritional treatment (St Johns Wort,
             SAM-e), lithium, other mood stabilizers, oral antipsychotics, depot antipsychotics
             within 12 weeks, beta blockers, thioridazine, pimozide, opiates, anxiolytics, and
             sedatives (with the exception of zolpidem, eszopiclone, and zaleplon). Also any
             treatment with any medication that the PI judges not acceptable for this study.

          -  Subject who is likely to require the use of the following medications: Chronic (for
             more than 2 weeks), regular nonsteroidal anti-inflammatory drugs (NSAID) use. Any use
             of aspirin (including low dose)

          -  Subject has taken non-psychoactive (prescription or non-prescription), dietary, or
             herbal products, with a narrow therapeutic index, that are metabolized via the
             cytochrome P450 3A4 or 2C9 pathway (warfarin), or transported via OATP1B1 or P-gp,
             within 2 weeks (or 5 half-lives, whichever is longer) prior to the Randomization
             Visit.

          -  Subject has taken other (non-psychoactive) prescription, non-prescription, dietary, or
             herbal products that are potent inducers or inhibitors of the cytochrome P450 3A4
             pathway for 2 weeks (or 5 half lives, whichever is longer) prior to the Randomization
             Visit.

          -  Subject has a stool positive for occult blood.

          -  Pregnancy or lactation

          -  Subjects who, in the opinion of the investigator, would be non compliant with the
             visit schedule or study procedures (e.g. illiteracy, planned vacations, or planned
             hospitalizations during the study).

          -  Previous treatment with CRF1 receptor antagonist

          -  Any laboratory abnormality that in the investigator's judgment is considered to be
             clinically significant (blood pressure, electrocardiogram (ECG), thyroid stimulating
             hormone (TSH), liver function test (LFT), etc.)

          -  Patients who are receiving exposure-based psychotherapy that targets PTSD symptoms

          -  Current or planned litigation or other actions related to secondary gain regarding the
             traumatic event

          -  Subject has clinical evidence of, or ECG results indicating any of the following at
             either screen or Randomization Visit unless repeat ECG shows that the parameter had
             returned to within normal range by the Randomization Visit:

               1. Corrected QT Interval (QTc) > 450 msec;

               2. any cardiac condition or ECG evidence that the investigator feels may predispose
                  the subject to ischemia or arrhythmia; or

               3. any ECG abnormality that, in the investigator's judgment, may pose a potential
                  safety concern