Evaluation of GSK561679 in Women With Post-Traumatic Stress Disorder

NCT01018992 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB00022717MH069056
• Study Type: interventional
• Target: 267
• Locations: 1 country
• Sites: 4

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).

Conditions

Stress Disorders, Post-Traumatic

Keywords

PTSD; Anxiety Disorder; Corticotropin releasing factor; Women

Outcome Measures

Primary Outcomes (1)

• Efficacy, Measured by Change in the Clinician-Administered PTSD Scale (CAPS) Score

  The CAPS is a semi-structured clinical interview providing a measure of the severity of PTSD symptoms. A severity score is calculated by summing the frequency and intensity scores for each of the 17 DSM-IV criteria symptoms. The severity of symptoms is rated on a scale from 0-4, where, 0 = Absent, 1 = Mild/subthreshold; 2 = Moderate/ threshold, 3 = Severe/markedly elevated and 4 = Extreme/ incapacitating. Scores may range from 0 (no symptoms) to 136 (severe symptoms). Change is the difference in scores between baseline and 6 weeks.

  Baseline, Week 6

Secondary Outcomes (3)

• Efficacy, Measured by Response Rate of at Least 50% Improvement in CAPS Score at the End of 6 Weeks as Compared to Baseline

  Baseline, Week 6

• Efficacy, Measured by Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Score

  Baseline, Week 6

• Safety, Measured by the Number of Subjects That Experienced an Adverse Event

  Week 6

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Adult women with DSM-IV defined PTSD will receive matching placebo for 6 weeks

Drug: Placebo

GSK561679

EXPERIMENTAL

Adult women with DSM-IV-defined PTSD will receive GSK561679 at a fixed dose of 350 mg/day for 6-weeks

Drug: GSK561679

Interventions

GSK561679 DRUG

GSK561679, oral administration, 350mg/day, 6 week administration

Also known as: CRF1 antagonist

GSK561679

Placebo DRUG

Matching placebo, oral administration, 1 pill/day for 6 weeks

Also known as: Sugar Pill

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Emory University: lead
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (4)

Stress and Health Research Program, San Francisco VA Medical Center, University of California San Francisco

San Francisco, California, 94121, United States

Location

Emory University

Atlanta, Georgia, 30306, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Jovanovic T, Duncan EJ, Kaye J, Garza K, Norrholm SD, Inslicht SS, Neylan TC, Mathew SJ, Iosifescu D, Rothbaum BO, Mayberg HS, Dunlop BW. Psychophysiological treatment outcomes: Corticotropin-releasing factor type 1 receptor antagonist increases inhibition of fear-potentiated startle in PTSD patients. Psychophysiology. 2020 Jan;57(1):e13356. doi: 10.1111/psyp.13356. Epub 2019 Feb 26.

  PMID: 30807663 DERIVED

• Pape JC, Carrillo-Roa T, Rothbaum BO, Nemeroff CB, Czamara D, Zannas AS, Iosifescu D, Mathew SJ, Neylan TC, Mayberg HS, Dunlop BW, Binder EB. DNA methylation levels are associated with CRF1 receptor antagonist treatment outcome in women with post-traumatic stress disorder. Clin Epigenetics. 2018 Nov 3;10(1):136. doi: 10.1186/s13148-018-0569-x.

  PMID: 30390684 DERIVED

• Dunlop BW, Rothbaum BO, Binder EB, Duncan E, Harvey PD, Jovanovic T, Kelley ME, Kinkead B, Kutner M, Iosifescu DV, Mathew SJ, Neylan TC, Kilts CD, Nemeroff CB, Mayberg HS. Evaluation of a corticotropin releasing hormone type 1 receptor antagonist in women with posttraumatic stress disorder: study protocol for a randomized controlled trial. Trials. 2014 Jun 21;15:240. doi: 10.1186/1745-6215-15-240.

  PMID: 24950747 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Anxiety Disorders

Interventions

NBI 77860; Sugars

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Carbohydrates

Limitations and Caveats

Limitations of this trial include short duration of treatment (6 weeks) and generalizability due to study population composed of only females.

Results Point of Contact

• Title: Dr. Boadie Dunlop
• Organization: Emory University

bdunlop@emory.edu

404-727-8474

Study Officials

• Boadie Dunlop, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 6, 2009
• First Posted: November 25, 2009
• Study Start: December 1, 2009
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: March 7, 2017
• Results First Posted: July 30, 2015

Record last verified: 2017-01

Locations

US (4)