Clinical trial NCT00733980: A Study of the Effects of a New Antidepressant Treatment (GSK561679) in Females With Major Depressive Disorder
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Keywords: Depressive Disorder, Major
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-08-13
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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.

Primary outcomes:
measure: Change From Randomization to the End of Treatment Phase (Week 6) in the Bech Melancholia Subscale (Bech) (Items 1, 2, 7, 8, 10 and 13) From the Hamilton Rating Scale for Depression (HamD17).
timeFrame: Randomization (Week 0) and Week 6
Secondary outcomes:
measure: Change From Randomization to Weeks 1, 2, and 4 in the Bech Melancholia Scale Score.
timeFrame: Randomization (Week 0) and Week 1, 2 and 4
measure: Change From Randomization to Weeks 1, 2, 4, and 6 in the Hamilton Anxiety Scale (HAM A)
timeFrame: Randomization (Week 0) and Week 1, 2, 4 and Week 6
measure: Change From Randomization to Weeks 1, 2, 3, 4, and 6 in the Inventory of Depressive Symptomatology-Self- Report (IDS-SR) Total Score.
timeFrame: Randomization (Week 0) and Week 1, 2, 3,4 and Week 6
measure: Change From Randomization to Weeks 1, 2, 4, and 6 in the Hamilton Rating Scale for Depression (HAMD-17)
timeFrame: Randomization (Week 0) and Week 1, 2, 4 and Week 6
measure: Percentage HAMD-17 Responders at Weeks 1, 2, 4, and 6.
timeFrame: Weeks 1, 2, 4, and 6.
measure: Time to Maintained Antidepressant Response at the End of Treatment Phase (Week 6)
timeFrame: Week 6
measure: Change From Randomization in the Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 4, and 6.
timeFrame: Randomization (Week 0) and Weeks 1, 2, 4, and 6.
measure: Percentage of Clinical Global Impression - Global Improvement (CGI-I) Responders at Weeks 1, 2, 4, and 6.
timeFrame: Weeks 1, 2, 4, and 6.
measure: Change From Randomization in the Medical Outcomes Study 12-item Sleep Module (MOS 12) at Week 6
timeFrame: Randomization (Week 0) and Week 6
measure: Change From Randomization in the Cohen Perceived Stress Scale (PSS) at Week 6.
timeFrame: Randomization (Week 0) and Week 6.
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to 28-day FU (18 months)
measure: Number of Participants With Vital Sign of Potential Clinical Importance (PCI)
timeFrame: Up to Week 10
measure: Number of Participants With Abnormal Urinalysis Data
timeFrame: Randomization (Week 0), Week 3, Week 6/ Early withdrawal (EW) and 28 Day follow-up (FU)
measure: Number of Participants With Abnormal Electrocardiograph (ECG) Values
timeFrame: Randomization (Week 0), Week 4, Week 6 and 28 Day follow-up
measure: Number of Participants With Abnormal Hematology Values of PCI-Platelet
timeFrame: Upto 28-day FU
measure: Number of Participants With Clinical Chemistry Laboratory Data Outside Reference Range
timeFrame: Upto Week 10
measure: Number of Participants With Hormonal Data of PCI
timeFrame: up to Week 10
measure: Discontinuation-Emergent Signs and Symptoms
timeFrame: At Week 6, 7-day (D) FU and 28-D FU
Other outcomes:
Locations:
city: Cerritos
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Torrance
country: United States
facility: GSK Investigational Site
state: California
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Marietta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Skokie
country: United States
facility: GSK Investigational Site
state: Illinois
city: Shreveport
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Rockville
country: United States
facility: GSK Investigational Site
state: Maryland
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Memphis
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Brown Deer
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Madison
country: United States
facility: GSK Investigational Site
state: Wisconsin
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: GSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing the attached study results summary with a conclusion.