Evaluation of the Efficacy of the CRF1 Antagonist GSK561679 in Women with Post-Traumatic Stress Disorder
This study will test the hypothesis of whether an antagonist at the corticotropin releasing factor type 1 receptor (i.e. GSK561679) is superior to placebo in reducing symptoms of PTSD. The study is being conducted at 2 sites in the United States: a site at Emory University, and one at Mount Sinai School of Medicine. About 150 women outpatients aged 21 to 65 who currently suffer from PTSD will be enrolled. Study participation could last for up to about 12 weeks.
The study is divided into 4 phases:
Phase 1 (Screening): a 1 week no drug screening period to assess study eligibility.
Phase 2 (Pre-Treatment Testing Period): Eligible patients will be enrolled into a 1 week Testing Phase, which will include neuropsychological and neurophysiological testing as well as blood draws and electrocardiogram.
Phase 3 (Treatment Period): Eligible patients will be enrolled in a two-armed 6-week period of double-blind placebo-controlled acute treatment. All subjects who continue to meet eligibility criteria will be randomized to one of two groups: GSK561679 (at a fixed dose of 350 mg/day) or placebo. Randomization will be performed at a 1:1 ratio into two treatment groups. Neuropsychological and neurophysiological testing will be repeated after 5 weeks of the double-blind treatment period.
Phase 4 (Follow-up Period): Safety follow-up visits will be conducted 1 week and 1 month after the end of the treatment Phase 3.
1. Women between the ages of 21 and 65
2. Fulfills DSM-IV criteria for a primary diagnosis of Post-traumatic stress disorder (PTSD)
3. Duration of PTSD is at least 3 months
4. Able to read and speak English
5. For women of reproductive age, must use of an effective birth control method or abstinence for the duration
6. Clinician-administered PTSD Scale score at Screening and Randomization visits of ≥ 50 on the CAPS
7. For women who have a history of peptic ulcer disease (PUD) with known etiology, evidence of effective treatment was provided with full eradication of ulcers and symptoms must be provided.
1. Lifetime diagnosis of a psychotic disorder (including schizophrenia), disorder, bipolar disorder, or obsessive compulsive disorder.
2. Current or past month participation in another clinical trial in which she is or will be exposed to an investigational or non-investigational drug or device.
3. A current significant unstable medical illness or organic brain impairment, including stroke, 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.
4. Patients who in the investigator’s judgment pose a current suicidal or homicidal risk
5. Substance abuse or dependence within the past 90 days, or testing positive for illegal substances.
6. Current diagnosis of anorexia or bulimia nervosa.
7. A documented history of hepato-biliary disease including evidence of current hepatitis infection, 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 (ALT, AST, ALP, total or direct bil > 1.5 x ULN, unless consistent with presumed or diagnosed Gilbert’s disease
8. Taking systemic corticosteroids within 2 weeks of the Randomization Visit
9. Treatment with any other psychoactive medication within 2 weeks of Screening visit, including psychoactive herbal or nutritional treatment.
10. Likely need for more than 2 weeks of regular NSAID use or any use of aspirin.
11. Taking any medication with with a narrow therapeutic index, that are metabolized via the cytochrome P450 3A4 or 2C9 pathway (e.g. warfarin), or transported via OATP1B1 or P-gp, within 2 weeks (or 5 half-lives, whichever is longer) prior to the Randomization Visit.
12. Taking any 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.
13. Stool positive for occult blood.
14. Pregnancy or lactation*
15. Participants who, in the opinion of the investigator, would be noncompliant with the visit schedule or study procedures (e.g. illiteracy, planned vacations, or planned hospitalizations during the study).
16. Previous treatment with CRF1 receptor antagonist
17. Any laboratory abnormality that in the investigator’s judgment is considered to be clinically significant (e.g. blood pressure, ECG, TSH, LFT, etc.)
18. Patients who are receiving exposure-based psychotherapy that targets PTSD symptoms
19. Current or planned litigation or other actions related to secondary gain regarding the traumatic event