A Study of the Effects of a New Antidepressant Treatment (GSK561679) in Females With Major Depressive Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00733980
First received: August 12, 2008
Last updated: August 30, 2012
Last verified: August 2012
  Purpose

This six-week study will evaluate the efficacy, safety and tolerability of GSK561679 compared to placebo in female subjects with major depressive disorder


Condition Intervention Phase
Depressive Disorder, Major
Drug: GSK561679
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Six-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Evaluating the Efficacy, Safety, and Tolerability of GSK561679 Compared to Placebo in Female Subjects, Diagnosed With Major Depressive Disorder

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change in score on a depression rating scale following 6 weeks of treatment. [ Time Frame: throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Endpoints related to changes in anxiety, sleep &stress throughout the treatment period,safety and tolerability including adverse events, vital signs, clinical laboratory values & ECGs throughtout the study & discontinuation symptoms during follow up. [ Time Frame: throughout the study ] [ Designated as safety issue: No ]

Enrollment: 150
Study Start Date: October 2008
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK561679 arm
Double blind GSK561679
Drug: GSK561679
GSK561679
Placebo Comparator: placebo arm
Double blind placebo
Other: Placebo
Placebo

Detailed Description:

This is a double-blind placebo controlled study to assess the CRF1 receptor antagonist, GSK561679, for treatment of depression in adult females diagnosed with Major Depressive Disorder (MDD). A treatment regimen of 350mg/day will be utilized to assess both efficacy and tolerability. Subjects will be randomized in equal numbers (n=75/arm) to the treatment arm and the placebo arm for a 6-week treatment period.

Efficacy will be assessed by determining the change from baseline in symptoms of MDD and anxiety utilizing the Bech Melancholia scale (Bech), Hamilton Rating Scale for Depression (HamD17), Inventory of Depressive Symptomatology-Self-Report (IDS-SR), Clinical Global Impression - Severity of Illness (CGI-S), Clinical Global Impression - Global Improvement (CGI-I), Medical Outcomes Study 12-item Sleep Module (MOS 12), Cohen Perceived Stress Test (PSS), Hamilton Anxiety Scale (HamA), and Dexamethasone Suppression Test (DST). Safety and tolerability will be assessed by determining the incidence of adverse events (AEs), vital signs, BMI, weight, clinical laboratory parameters, including ECGs, during the treatment and pre & post-treatment phases, and Discontinuation Emergent Signs and Symptoms (DESS). In addition, the incidence of suicidality will be assessed by the Columbia Suicide Severity Rating Scale (C-SSRS).

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Female outpatients aged 25-64 years, inclusive.
  • Subjects must have the ability to comprehend the consent form, and provide informed consent.
  • Subject currently meets the diagnosis for MDD (without psychotic features), single episode or recurrent, as defined in the DSM-IV-TR, diagnosed with SCID-CT (Structural Clinical Interview for DSM-IV Axis I disorders - Clinical Trials Version) as assessed * by a physician with adequate training in psychiatry (e.g., Board Certification in psychiatry in the US or equivalent local qualification in other countries)
  • Subject must, in the investigator's opinion based on clinical history, have met DSM IV-TR criteria for their current major depressive episode for at least 4 weeks but for no greater than 24 months.
  • Subject has an IVRS HamD17 total score ≥ 23 at the Screening and Randomization Visits and the HAMD17 score is confirmed to be at least 20 by the Independent Efficacy Rater at the Screening and Randomization Visits.
  • The subject is eligible to enter and participate in this study if she is not lactating and:
  • Is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal [defined as one year without menses]); is surgically sterile [via hysterectomy and/or removal of the ovaries] or, is of child-bearing potential, has a negative pregnancy test at both screening and baseline (prior to investigational product administration), and agrees to acceptable methods of contraception.

Exclusion Criteria

  • Symptoms of the presenting illness which are better accounted for by another diagnosis*; or
  • A current DSM-IV-TR Axis I diagnosis of Dementia; or
  • Antisocial or Borderline Personality Disorder or other current DSM-IV-TR Axis II diagnosis that would suggest unresponsiveness to pharmacotherapy or non-compliance with the protocol; or
  • A current (or within 12 months prior to the Screening visit) diagnosis of anorexia nervosa or bulimia; or
  • A lifetime history of Schizophrenia, Schizoaffective Disorder, or a Bipolar Disorder.
  • Subject has an unstable medical disorder or a disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of GSK561679 or may pose a safety concern, or interfere with the accurate assessment of safety or efficacy.
  • Subject has initiated psychotherapy within one month prior to the Screening visit, or plans to initiate psychotherapy during the trial. Subjects who present with their current MDD diagnosis despite longer-term psychotherapy (i.e., greater than three months prior to the Screening visit) and who agree to maintain the same therapy schedule during the trial may be included.
  • Subject has received vagus nerve stimulation, electroconvulsive therapy, or transcranial magnetic stimulation within the six months prior to the Screening visit.
  • Subject has previously failed adequate therapeutic courses of pharmacotherapy for MDD (e.g., maximum-labeled/tolerated doses for ≥ 4 weeks) from two different classes of antidepressants.
  • Subject, who, in the investigator's judgement, poses a homicidal or serious suicidal risk, has had any previous suicide attempt (including aborted, interrupted or ineffective attempts) or who has ever been homicidal.
  • Subject has no contact with an adult on a daily basis (i.e., subjects who are not living with at least one other adult or subjects who do not have an adult who contacts them on a daily basis). This criterion only applies to sites in Canadian sites and others where this is a local requirementa.
  • Subject has a positive urine test at screening for illegal drug use and/or history of substance abuse or dependence (alcohol or drugs as defined by DSM-IV TR criteria) within the past 12 months. Subject has a blood alcohol level of ≥ 15mg/dL (0.015%) at the Screening Visit. If a subject has a positive blood alcohol or positive illegal drug results, the subject is provisionally excluded and the test cannot be repeated without prior approval of the GSK medical monitor. NOTE: Subjects must be told to avoid consumption of alcoholic beverages for at least eight hours prior to the Screening Visit. The use of alcohol by subjects participating in the study is not recommended.
  • Subject has any laboratory abnormality that in the investigator's judgement is considered to be clinically significant and could potentially affect subject safety or study outcome.
  • Subject has a systolic blood pressure (SBP) > 160mmHg or a diastolic blood pressure (DBP) ≥ 100 mmHg verified by repeated measurement at the Screening or Randomization visit.
  • Subject is (a) currently participating in another clinical study in which the subject is or will be exposed to an investigational or non-investigational drug or device; or (b) has participated in a clinical study for an illness unrelated to depression/anxiety within the preceding month; or (c) has participated in a clinical study related to depression/anxiety within the preceding six months.
  • 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) at Screening, and/or clinically significant hepatic enzyme elevation 13.Subjects who are not euthyroid as evidenced by normal TSH (subjects maintained on thyroid medication must be euthyroid for a period of at least six months prior to the screen visit).
  • Subject has a positive serum Human Chorionic Gonadotropin (HCG) pregnancy test at screen visit, a positive urine dipstick test at randomization, or who is lactating or planning to become pregnant within the next 13 weeks following the Screen Visit.
  • 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 Randomisation Visit. (The ECG may be repeated to see if the parameter returns to within range):

    • QTc > 450 msec;
    • any cardiac condition or ECG evidence that the investigator feels may predispose the subject to ischemia or arrhythmia; or
    • any ECG abnormality that, in the investigator's judgment, may pose a potential safety concern.
  • Subject has taken other psychoactive drugs within one week prior to the ScreeningScreening Randomization Visit
  • Subject has taken systemic corticosteroids acutely within two weeks or chronically within the last 6 months of the Randomization Visit (NOTE: Topical hydrocortisone and inhaled corticosteroids are allowed).
  • Subject has taken other (non-psychoactive) prescription, non-prescription, dietary, or herbal products metabolized via the cytochrome P450 3A4 pathway, or P-gp substrates with a narrow therapeutic index 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 previously participated in an investigational trial involving GSK561679 or closely related compounds.
  • Subject has a history of allergic reaction to, or significant adverse effects from excipients in the GSK561679 tablet.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00733980

Locations
United States, California
GSK Investigational Site
Cerritos, California, United States, 90703
GSK Investigational Site
San Diego, California, United States, 92108
GSK Investigational Site
Torrance, California, United States, 90502
United States, Florida
GSK Investigational Site
Jacksonville, Florida, United States, 32216
GSK Investigational Site
Miami, Florida, United States, 33125
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30322
GSK Investigational Site
Marietta, Georgia, United States, 30060
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60612
GSK Investigational Site
Skokie, Illinois, United States, 60076
United States, Louisiana
GSK Investigational Site
Shreveport, Louisiana, United States, 71104
United States, Maryland
GSK Investigational Site
Rockville, Maryland, United States, 20852
United States, New Mexico
GSK Investigational Site
Albuquerque, New Mexico, United States, 87109
United States, North Carolina
GSK Investigational Site
Raleigh, North Carolina, United States, 27609
United States, Ohio
GSK Investigational Site
Cincinnati, Ohio, United States, 45219-0516
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
GSK Investigational Site
Memphis, Tennessee, United States, 38119
United States, Wisconsin
GSK Investigational Site
Brown Deer, Wisconsin, United States, 53223
GSK Investigational Site
Madison, Wisconsin, United States, 53719
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00733980     History of Changes
Other Study ID Numbers: 106139
Study First Received: August 12, 2008
Last Updated: August 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Depressive Disorder, Major

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014