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Safety and Efficacy Study in Patients With Major Depressive Disorder

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00896363
First Posted: May 11, 2009
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
The purpose of this study is to test if GSK163090 can reduce the symptoms of depression. The safety and how well the body can handle the drug will also be investigated. The study will be conducted in Russia in hospitalised patients with severe depression. GSK163090 will be compared with placebo, which looks like the study drug but does not contain any active substance. Subjects will be given either the study drug or the matching placebo.

Condition Intervention Phase
Depressive Disorder Drug: GSK163090 Tablets Drug: GSK163090 Placebo Tablets Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Study Evaluating the Efficacy and Safety of GSK163090 in Subjects With Major Depressive Disorder

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline in the Hamilton Depression Rating Scale (HAMD17), on Day 14 and 42 [ Time Frame: Baseline (Day 1, pre-dose), Day 14 and Day 42 ]
    HAMD-17 is a 17-item scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and co-morbid anxiety symptoms. The 17 items were rated on either a 5-point (0-4) or a 3-point (0-2) scale. In general, the 5 point scale items use a rating of 0=absent; 1=doubtful to mild; 2=mild to moderate; 3=moderate to severe; 4=very severe. The 3-point scale items use a rating of 0=absent; 1=probable or mild; 2=definite. The total HAMD-17score ranges from 0 (not ill) to 52 (severely ill). The highest possible score was 52, which represented the most severe measure of depression; the lowest possible score was 0, which represents an absence of depression. Baseline was defined as the assessment done on Day 1 (pre-dose). Change from baseline in total Score was the difference between HAMD total score at the time point being analyzed to Day 1.

  • Change from baseline in bech melancholia subscale (BECH 6) scale, on Day 14 and 42 [ Time Frame: Baseline (Day 1, pre-dose), Day 14 and Day 42 ]
    The bech melancholia is sum of scores on 6 items- depressed mood, feelings of guilt, work and activities, retardation, anxiety psychic, somatic symptoms general (items 1, 2, 7, 8, 10 and 13 respectively). Each item having 5 responses. The items are rated on a scale of 0-4, where 0=absent; 1=doubtful to mild; 2=mild to moderate; 3=moderate to severe; 4=very severe. Total possible score is 0-24. where the lowest possible score was 0, which represented an absence of depression and higher scores reflecting greater severity of diseases. Baseline was defined as the assessment done on Day 1. Change from baseline was the difference between BECH 6 scale at the time point being analyzed to randomization.

  • Change from baseline in Quick Inventory of depressive symtomatology - self rated (QIDS-SR) Scale, on Day 14 and 42 [ Time Frame: Baseline (Day 1, pre-dose), Day 14 and Day 42 ]
    The QIDS-SR is a 16-item, participant-rated short form of the Inventory of Depressive Symptomatology that assesses 9 domains: sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle, and late insomnia or hypersomnia), appetite/weight increase/decrease and psychomotor agitation/retardation. A total score was obtained by summing scores on each domain. the scores ranges from 0 (none) to 27 (very severe), where the highest possible score was 27, which represented the most severe measure of depression; the lowest possible score was 0, which represents an absence of depression. Baseline was defined as the assessment done on Day 1. Change from Randomization in total score was the difference between QIDS total score at the time point being analyzed to randomization.

  • Number of participants with suicidal behavior and suicidal ideation subscales of the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to Day 52 ]
    The C-SSRS was a clinician-rated scale that evaluated severity and change of suicidality by integrating both behaviour and ideation. The 2 of 3 sections of the scale were suicidal behavior and suicidal ideation. For suicidal behaviour participants were scored as non-suicidal-0, preparatory acts or behavior communicating ideation-01, aborted attempt-2, interrupted attempt-3 or actual attempt-4. The score ranges from 0-4, where 0 was absence of suicidal behavior and 4 being the most severe form of suicidal behavior. On the Suicidal Ideation scale, participants were scored as non-suicidal-0, wish to be dead-1, non-specific active suicidal thoughts-2, active suicidal ideation with associated thoughts of methods without intent-3, active suicidal ideation with some intent to act on suicidal thoughts without clear plan-4, active suicidal ideation with plan and intent-5. The score ranges from 0-5, where 0 was absence of suicidal ideation and 5 being the most severe form of suicidal ideation.

  • Number of participants with Abnormal hematology values of clinical concern range (CCR). [ Time Frame: Up to Day 42 ]
    Only those parameters for which at least one value of CC was reported were summarized. Pre-defined limits of CC (CC Low [relative to the lower limit of normal], CC High [relative to the upper limit of normal]) were: hemoglobin (Hb): > 25, 180; hematocrit (Hct): > 0.075, 0.54; absolute neutrophil count (ANC): < 1.5, NA; platelet: < 100, > 550; white blood cells (WBC): < 3,> 20

  • Number of participants with abnormal chemistry values of CCR [ Time Frame: Up to Day 42 ]
    Only those parameters for which at least one value of CC was reported were summarized. Pre-defined limits of CC (CC Low [relative to the lower limit of normal], CC High [relative to the upper limit of normal]) were: albumin (unit: gram per liter): < 30, NA; alanine aminotransferase (ALT): NA, >= 3 times upper limit of normal; aspartate aminotransferase (AST): NA, >= 3 times upper limit of normal; total bilirubin: NA, >=1.5 times upper limit of normal; calcium: < 2.0, > 2.75; gamma glutamyl transferase (GGT): < 3.0, > 9; potassium: < 3.0, > 5.5; magnesium: < 0.5, > 1.23.

  • Change from Baseline in liver chemistry -Alkaline Phosphatase, ALT, AST, GGT [ Time Frame: Baseline (screening) up to Day 42 ]
    Clinical liver chemistry parameters of Alkaline Phosphatase , ALT, AST, GGT were assessed on screening, Day 7, Day 14, Day 28 and Day 42. Screening was defined as Baseline. Change from Baseline in liver chemistry was the difference between the value at time point analyzed and screening.

  • Change from Baseline in liver chemistry- Direct Bilirubin and Total Bilirubin [ Time Frame: Baseline (screening) up to Day 42 ]
    Liver chemistry parameters: Direct Bilirubin and Total Bilirubin were assessed on screening, Day 7, Day 14, Day 28 and Day 42. Screening was defined as Baseline. Change from Baseline in liver chemistry was the difference between the value at time point analyzed and screening.

  • Number of participant of Urinanalysis assessment over period [ Time Frame: Screening (Day -10 to -2) ]
    Urinalysis parameters included: Urine Occult Blood, Urine Ketones, Urine Ketones. data for number of participants with abnormal urinanalysis parameters was reported by dipstick method. dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. dipstick test gives results in a semi-quantitative manner, and results can be read as negative, Trace, 1+, 2+, and 3+, indicating proportional concentrations in the urine sample. Urine occult blood dipstick and urine general dipstick were semi quantitative results. Urine glucose and urine ketones dipstick results were in milimole per liter, urine protein dipstick results were in gram per liter.

  • Change from Baseline in electrocardiogram (ECG) Values -PR Interval, QRS Duration, QT Interval, QTcB, QTcF, RR Interval [ Time Frame: Baseline (Day 1) and up to Day 42 ]
    Data for change from Baseline was reported for PR Interval, QRS Duration, QT Interval, QTcB, QTcF, and RR Interval. 12-lead ECGs was obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and QTcB ,QTcF, and RR intervals. Day -1 evening (PM) was the Baseline for participants with only Day -1 records. Day 1 PM Dose was the Baseline for participants with Day 1 records. Baseline was the mean of replicate assessments. Change from Baseline was the difference between the value at the time point analyzed and baseline value.

  • Mean of change from Baseline in systolic and diastolic blood pressure (BP) [ Time Frame: Baseline (Day 1) and up to Day 52 ]
    Semi-supine systolic and diastolic blood pressure was assessed at the specified time points. Measurements were taken after the participant has been semi-supine for at least 5 minutes. BP was measured at least every hour until the values were within the normal range. Day 1 was Baseline and change from Baseline was difference between the value at the time point analyzed and baseline value.

  • Mean of change from Baseline in heart rate [ Time Frame: Baseline (Day 1) and up to Day 52 ]
    Heart rate is the speed of the heartbeat measured by the number of contractions of the heart per minute, (beats per minute). Heart rate was assessed at the specified time points. Measurements were taken after the participant has been semi-supine for at least 5 minutes. Day 1 was Baseline and change from Baseline was difference between the value at the time point analyzed and baseline value.

  • Number of participants with all adverse events (AEs), and serious adverse events (SAEs) [ Time Frame: Up to Day 52 ]
    Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.


Secondary Outcome Measures:
  • Mean Last observed quantifiable concentration (Ct) of GSK163090 Over the period [ Time Frame: Day 4 (AM pre-dose), Day 7 (AM and PM pre-dose), Day 10 (AM and PM pre-dose), Day 14 (AM and PM pre-dose), Day 21 (AM pre dose), Day 28 (AM pre dose), Day 42 (AM pre-dose and 4-6 h post AM dose) ]
    Ctrough is defined as trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration]). Concentration was reported at specified time points.

  • Area under concentration-time curve (AUC) at steady state [ Time Frame: Day 4 (AM pre-dose), Day 7 (AM and PM pre-dose), Day 10 (AM and PM pre-dose), Day 14 (AM and PM pre-dose), Day 21 (AM pre dose), Day 28 (AM pre dose), Day 42 (AM pre-dose and 4-6 h post AM dose) ]
    PK samples were supposed to be collected to estimate individual specific parameters like AUC however it was not analyzed.

  • Average concentration (Cave) at steady state [ Time Frame: Day 4 (AM pre-dose), Day 7 (AM and PM pre-dose), Day 10 (AM and PM pre-dose), Day 14 (AM and PM pre-dose), Day 21 (AM pre dose), Day 28 (AM pre dose), Day 42 (AM pre-dose and 4-6 h post AM dose) ]
    PK samples were supposed to be collected to estimate individual specific parameters like Cave. however it was not analyzed.

  • Preliminary pharmacokinetic/ pharmacodynamic (PK/PD)relationships for GSK163090 in participants with MDD. [ Time Frame: Day 4 (AM pre-dose), Day 7 (AM and PM pre-dose), Day 10 (AM and PM pre-dose), Day 14 (AM and PM pre-dose), Day 21 (AM pre dose), Day 28 (AM pre dose), Day 42 (AM pre-dose and 4-6 h post AM dose) ]
    PK/PD relationships for GSK163090 in participants with MDD was not analyzed.


Enrollment: 99
Study Start Date: April 1, 2009
Study Completion Date: February 9, 2010
Primary Completion Date: February 1, 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active
Parallel Group - High Dose Arm, Low Dose Arm
Drug: GSK163090 Tablets
Developed for the treatment of Major Depressive Disorder
Placebo Comparator: Placebo
Parallel Group
Drug: GSK163090 Placebo Tablets
Developed for the treatment of Major Depressive Disorder

Detailed Description:
This is a randomised, multi-centre, double-blind, placebo-controlled, repeat dose, parallel group study in male and female patients with severe depression requiring hospitalization. Efficacy, safety and tolerability will be assessed in three treatment arms. The study will consist of a screening period, a treatment phase (up to 6 weeks) and a post-treatment follow-up visit. The study duration from screening to follow up will be approximately 9 weeks. Subjects who pass screening will be randomized on Day 1 to one of three treatment arms (low dose arm, high dose arm or placebo). Each treatment arm will contain approximately 50 subjects. The subject's depressive symptoms will be assessed using the HAMD17- CR.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Currently have severe depression (Major Depressive Disorder - without psychotic features)
  • meet criteria (DSM IV-TR ) for current major depressive episode for at least 4 weeks but for no greater than 24 months
  • depression questionnaire (HAMD17) total score greater than or equal to 24
  • subject must read and able to give written informed consent
  • male or female 18 to 64 years
  • use appropriate birth control method
  • BMI 18.8 - 35.0 kg/m2 (inclusive)

Exclusion Criteria:

  • Primary diagnosis of other psychiatric disorders
  • thoughts of killing ones self or someone else
  • taking psychiatric medicine or therapy within the six months
  • Has previously failed an adequate course of medication for MDD from two different classes of antidepressants.
  • Unstable medical disorder or a disorder that would interfere with the action of the drug
  • Abuse of alcohol or drugs
  • Past history of serotonin syndrome or a history of clinical significant intolerance of SSRIs (class of drugs used for depression).
  • History of migraine headaches that respond to treatment with triptan medication.
  • History of a clinically significant abnormality of the neurological system (including dementia and other cognitive disorders or significant head injury) or any history of seizure (excluding febrile seizure).
  • Currently taking part in another clinical study or has done so within six months
  • Pregnant, planning to become pregnant shortly or breastfeeding
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00896363


Locations
Russian Federation
GSK Investigational Site
Ekaterinburg, Russian Federation, 620030
GSK Investigational Site
Kemerovo, Russian Federation, 650036
GSK Investigational Site
Lipetsk Region, Russian Federation, 399083
GSK Investigational Site
Moscow, Russian Federation, 119992
GSK Investigational Site
Nizhny Novgorod, Russian Federation, 603107
GSK Investigational Site
Saint Petersburg, Russian Federation, 190005
GSK Investigational Site
Saint Petersburg, Russian Federation, 191180
GSK Investigational Site
Saint-Petersburg, Russian Federation
GSK Investigational Site
Saratov, Russian Federation, 410060
GSK Investigational Site
Smolensk, Russian Federation, 214 019
GSK Investigational Site
St-Petersburg, Russian Federation, 197341
GSK Investigational Site
St. Petersburg, Russian Federation, 190121
GSK Investigational Site
St. Petersburg, Russian Federation, 194044
GSK Investigational Site
St.Petersburg, Russian Federation, 193167
GSK Investigational Site
Tomsk, Russian Federation, 634014
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 109035
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 109035
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 109035
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 109035
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 109035
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 109035
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 109035
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00896363     History of Changes
Other Study ID Numbers: 109035
First Submitted: May 7, 2009
First Posted: May 11, 2009
Last Update Posted: October 12, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:
anti-depressant
Severe Depression
Efficacy
Major Depressive Disorder
Major Depressive Episode

Additional relevant MeSH terms:
Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms