Please select the eligibility criteria that correspond to the clinical trial below.
Title: Evaluation of the Efficacy of the CRF1 Antagonist GSK561679 in Women With Post-traumatic Stress Disorder
Brief 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).


Options:
A: Key Inclusion Criteria:

* Veteran or civilian adult outpatients 18-55 years of age, with primary PTSD as defined by Diagnostic and Statistical manual of Mental Disorders-IV (DSM-IV) for at least 6 months
* Must be in general good health-confirmed by medical history, physical examination, and screening laboratory results
* Negative urine drug screen for drugs of abuse
* Negative urine pregnancy test for females of childbearing potential
* Sexually active participants are required to use a medically acceptable form of birth control

Key Exclusion Criteria

* Clinically unstable medical disease; progressive CNS disorder/disease; history of seizures (except childhood febrile seizure); moderate or severe traumatic brain injury (TBI)
* Females who are pregnant or currently breast feeding
* Current or past psychotic disorder, bipolar Type I disorder, or dementia
* Participants with recent drug abuse or dependency (excluding nicotine and caffeine)
* Participants unwilling to comply with the required alcohol prohibition during the trial
* Current suicidal or homicidal ideation necessitating intervention, and those with a history of suicide attempt in the past 10 years
* Participants with pending litigation related to the traumatic event
* Participants who are unwilling to withhold grapefruit or grapefruit juice for the duration of the study
* Participants receiving psychotherapy without a stable paradigm for at least 3 months
* Non-English speaking participants.
B: 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
C: Inclusion Criteria:

* Primary diagnosis of PTSD
* In grades 6-12
* No change in medication regimen for more than 6 weeks

Exclusion Criteria:

* Diagnosis of ADHD, conduct disorder, thought disorder, or bipolar disorder
D: Inclusion Criteria:

* Men or women, 18-65 years of age;
* Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document;
* Participants must fulfill DSM-5 criteria for current civilian or combat-related PTSD
* Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year);
* Women of childbearing potential must have a negative pregnancy test at screening and prior to each intravenous infusion;
* Participants must be able to identify a family member, physician, or friend (i.e. someone who knows them well) who will participate in a Treatment Contract (and e.g. contact the study physician on their behalf in case manic symptoms or suicidal thoughts develop).

Exclusion criteria:

* Women who plan to become pregnant, are pregnant or are breast-feeding
* Serious, unstable medical illnesses such as hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, including gastro-esophageal reflux disease, obstructive sleep apnea, history of difficulty with airway management during previous anesthetics, ischemic heart disease and uncontrolled hypertension, and history of severe head injury;
* Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
* Renal impairment, as reflected by a BUN \>20 mg/dL, and/or creatinin clearance of \>1.3 mg/dL;
* Thyroid impairment, as reflected by TSH\> 4.2 mU/L Patients with uncorrected hypothyroidism or hyperthyroidism;
* Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first infusion day;
* Use of evidence-based individual psychotherapy (such as prolonged exposure) during the study;
* History of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome; History of one or more seizures without a clear and resolved etiology;
* History of (hypo)mania;
* Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder;
* Drug or alcohol abuse or dependence within the preceding 3 months
* Previous recreational use of ketamine or PCP;
* Current diagnosis of bulimia nervosa or anorexia nervosa;
* Diagnosis of schizotypal or antisocial personality disorder
* Patients judged clinically to be at serious and imminent suicidal or homicidal risk.
* A blood pressure of one reading over 160/90 or two separate readings over 140/90 at screen or baseline visits
* Patients who report current treatment with a benzodiazepine, an opioid medication, or a mood stabilizer (such as valproic acid or lithium) within 2 weeks prior to randomization

Answer: B