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Clinical Study to Test a New Drug to Treat Major Depression (PKI113009)

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ClinicalTrials.gov Identifier: NCT00976560
Recruitment Status : Completed
First Posted : September 14, 2009
Results First Posted : November 14, 2017
Last Update Posted : November 14, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Depressive Disorder, Major
Interventions Drug: GW856553
Other: Placebo
Enrollment 128
Recruitment Details The study was conducted between 25 Sep 2009 to 7 July 2010. The study was conducted at 21 centers in 5 countries (Bulgaria [4], Estonia [1], Germany [7], Russia [5], United States [4]).
Pre-assignment Details A total of 128 participants of both the gender, with major depressive disorder (MDD), having at least one previous major depressive episode in history and currently undergoing a recurrence, of age group 18 to 60, were enrolled globally. A total of 231 participants were screened of which 103 were screen-failures.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks. Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Period Title: Overall Study
Started 64 64
Completed 50 51
Not Completed 14 13
Reason Not Completed
Adverse Event             5             5
Lack of Efficacy             3             5
Protocol Violation             1             0
Lost to Follow-up             1             0
Physician Decision             2             0
Withdrawal by Subject             2             3
Arm/Group Title Placebo GW856553 7.5 mg BID Total
Hide Arm/Group Description Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks. Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks. Total of all reporting groups
Overall Number of Baseline Participants 64 64 128
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
18 to 60 years Number Analyzed 64 participants 64 participants 128 participants
64
 100.0%
64
 100.0%
128
 100.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 64 participants 128 participants
Female
37
  57.8%
39
  60.9%
76
  59.4%
Male
27
  42.2%
25
  39.1%
52
  40.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 64 participants 128 participants
American Indian or Alaska Native
1
   1.6%
0
   0.0%
1
   0.8%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   4.7%
1
   1.6%
4
   3.1%
White
60
  93.8%
63
  98.4%
123
  96.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change From Randomization (Week 0) Associated With GW856553 Versus Placebo at Week 6 in the Bech (6-item HAMD-17 [Hamilton Depression Rating Scale]) Score.
Hide Description HAMD-17 has 17 questions. The HAMD-17 Total Score was calculated by summing the individual response scores over the 17 individual components of the interview. The highest possible score was 52, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. There were 9 five point questions and 8 three point questions. The responses to the individual questions had values of 0-2 (three points response) or 0-4 (five points response). The BECH scale was extracted from the HAMD-17 and comprises of 6 items out of which 5 are 5 point questions and 1 is 3 point question. The Bech Total Score was calculated by summing the individual response scores and ranged from 0 to 22, with higher scores indicating more severe depression. Week 0 values were considered as Baseline.The change from randomization was analysed using suitable Bayesian mixed-effects model repeated measures (BMMRM) assuming missing at random (MAR).
Time Frame At Week 6
Hide Outcome Measure Data
Hide Analysis Population Description

Intent-to-Treat (ITT) - It comprised of all randomised participants who received at least one dose of study medication and had at least one post-dose efficacy assessment.

Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 50 51
Mean (Standard Deviation)
Unit of Measure: Scores on scale
-6.5  (3.62) -5.6  (3.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GW856553 7.5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method BMMRM
Comments Bayesian Mixed Effects Model Repeated Measures (BMMRM)
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.60
Confidence Interval (2-Sided) 95%
-2.54 to 1.35
Parameter Dispersion
Type: Standard Deviation
Value: 0.990
Estimation Comments Prior distribution of N(-4.1, 6.4009) incorporated into the posterior for the treatment difference at Week 6. The presented Confidence Interval is Highest Probability Density (HPD).
Other Statistical Analysis Posterior probability of the treatment difference being greater than 1.6 points in favor of GW856553 7.5mg BID as compared to placebo at Week 6 is 15.46 and for 0 is 72.98 and for 2 is 7.87.
2.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. The AEs row include participants with SAEs.
Time Frame 6 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population - It comprised of all participants who receive at least one dose of study medication.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 64 64
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
28
  43.8%
26
  40.6%
SAEs
1
   1.6%
1
   1.6%
3.Secondary Outcome
Title Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score
Hide Description Suicidility was defined as participants with major depressive disorder who experienced worsening of their depression and/or the emergence of suicidal ideation and behavior. Number of partcipants who experienced suicidality were reported. On the Suicidal Ideation scale of the Columbia Suicide-Severity Rating Scale (C-SSRS) participants were scored as “non-suicidal” (00), “wish to be dead” (01), “non-specific active suicidal thoughts” (02), “active suicidal ideation with associated thoughts of methods without intent” (03), “active suicidal ideation with some intent to act on suicidal thoughts without clear plan” (04) and “active suicidal ideation with plan and intent” (05), based on the most severe score (5 being the most severe).Suicidal ideation of type 4 or 5 in the C-SSRS was categorized as suicidility here.
Time Frame Upto Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 64 64
Measure Type: Count of Participants
Unit of Measure: Participants
Week 1, Non-suicidal Number Analyzed 55 participants 57 participants
55
 100.0%
57
 100.0%
Week 2, Non-suicidal Number Analyzed 54 participants 55 participants
54
 100.0%
55
 100.0%
Week 3, Non-suicidal Number Analyzed 49 participants 54 participants
49
 100.0%
54
 100.0%
Week 4, Non-suicidal Number Analyzed 50 participants 54 participants
50
 100.0%
54
 100.0%
Week 5, Non-suicidal Number Analyzed 49 participants 50 participants
49
 100.0%
50
 100.0%
Week 6, Non-suicidal Number Analyzed 50 participants 49 participants
50
 100.0%
49
 100.0%
4.Secondary Outcome
Title Number of Participants With Abnormal Haematology and Clinical Chemistry Values
Hide Description Samples for haematology and clinical chemistry were collected on Weeks 1, 5 and 6. The analyzed haematological parameters were platelet count, red blood cells count, white blood cells count, reticulocyte count, hemoglobin and hematocrit. The analyzed clinical chemistry parameters were urea, creatinine, glucose (fasting), sodium, lactate dehydrogenase (LDH), potassium, chloride, calcium, triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, creatine kinase (CK), total and direct bilirubin, albumin, total protein and total cholesterol. Number of participants with any abnormal haematological or clinical chemistry parametrs are summarized here.
Time Frame Upto Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 64 64
Measure Type: Count of Participants
Unit of Measure: Participants
Glucose High, Week 6 Number Analyzed 44 participants 46 participants
1
   2.3%
0
   0.0%
Total Bilirubin High, Week 4 Number Analyzed 45 participants 51 participants
1
   2.2%
0
   0.0%
5.Secondary Outcome
Title Number of Participants With Abnormal Vital Signs (Blood Pressure, Heart Rate)
Hide Description Vital signs including systolic and diastolic blood pressure and heart rate were taken from day 1 upto follow-up visit. Number of participants with abnormal systolic blood pressure, diastolic blood pressure and heart rate values were summarized.
Time Frame Up to follow-up Visit (Day 53)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 64 64
Measure Type: Count of Participants
Unit of Measure: Participants
Low Diastolic blood pressure, Week 4 Number Analyzed 53 participants 56 participants
1
   1.9%
0
   0.0%
High Systolic blood pressure, Week 2 Number Analyzed 59 participants 60 participants
1
   1.7%
0
   0.0%
6.Secondary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Hide Description ECG was obtained at Week 2 and Week 6. ECG was recorded using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and Corrected QT (QTc) intervals (Bazett’s correction was applied to QTc measurements). Number of participants with abnormal ECG readings are summarized.
Time Frame Up to follow-up Visit (Day 53)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 64 64
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title Changes From Randomization (Week 0)in IL-6 and TNF-alpha Associated With GW856553 Versus Placebo at Week 1 and Week 6 in the Morning Plasma Levels
Hide Description Interlukin-6 (IL-6) and Tumor Necrosis Factor-Alpha (TNF-alpha) from the participants with Major Depressive Disorder (MDD) were evaluated and analyzed using suitable mixed-effects model repeated measures (MMRM). Exploratory analysis on plasma levels of IL-6 and TNF-alpha were performed. Week 0 values were considered as Baseline.The change from Baseline was calculated by subtracting the baseline values from the individual post-randomisation values.
Time Frame Upto Week 6
Hide Outcome Measure Data
Hide Analysis Population Description

Intent-to-Treat (ITT) Population - It consists of all randomised subjects who receive at least one dose of study medication and had at least one post-dose efficacy assessment.

Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 62 63
Mean (Standard Deviation)
Unit of Measure: picogram/mililitre (pg/mL)
IL-6, Week 1, Predose Number Analyzed 58 participants 62 participants
-1.06  (8.04) -0.27  (4.36)
IL-6, Week 1, 3 hours (hrs) Number Analyzed 61 participants 63 participants
-1.86  (9.72) -1.57  (4.30)
IL-6, Week 6, Predose Number Analyzed 50 participants 51 participants
-0.67  (11.29) -0.96  (5.68)
IL-6, Week 6, 3 hrs Number Analyzed 50 participants 51 participants
-0.11  (8.93) -0.98  (9.36)
IL-6, Early Withdrawal Number Analyzed 9 participants 11 participants
-7.44  (15.54) 0.35  (4.52)
TNF-alpha, Week 1, Predose Number Analyzed 56 participants 60 participants
1.04  (9.65) -0.26  (1.43)
TNF-alpha, Week 1, 3 hrs Number Analyzed 59 participants 60 participants
1.41  (12.61) -0.65  (1.61)
TNF-alpha, Week 6, Predose Number Analyzed 48 participants 49 participants
3.80  (28.78) -0.10  (1.57)
TNF-alpha, Week 6, 3 hrs Number Analyzed 49 participants 49 participants
4.11  (29.20) -0.63  (1.49)
TNF-alpha, Eary Withdrawal Number Analyzed 9 participants 11 participants
0.31  (0.96) -1.07  (2.24)
8.Secondary Outcome
Title Change From Randomisation Bech Total Score: Bech Score
Hide Description HAMD-17 has 17 questions. The BECH scale was extracted from the HAMD-17 and comprises of 6 items out of which 5 are 5 point questions and 1 is 3 point question. The Bech scale was extracted from the HAMD-17 and comprised of 6 items out of which 5 were 5 point questions and 1 was 3 point question. The Bech Total Score was calculated by summing the individual response scores and ranged from 0 to 22, with higher scores indicating more severe depression. Due to the small number of items, missing data was not imputed for the Bech Total Score. If any of the 6 items were missing, the total score was not calculated at that visit. The change from randomization was analysed using suitable Bayesian Mixed-Effects Models for Repeated Measures (BMMRM) assuming missing at random MAR.
Time Frame Up to Follow-up visit (Day 53)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 62 63
Mean (Standard Deviation)
Unit of Measure: Scores on scale
Week 1 Number Analyzed 62 participants 63 participants
-1.2  (2.14) -1.6  (2.47)
Week 2 Number Analyzed 59 participants 60 participants
-2.5  (2.73) -2.2  (2.91)
Week 3 Number Analyzed 54 participants 58 participants
-3.9  (3.20) -3.4  (3.07)
Week 4 Number Analyzed 53 participants 57 participants
-5.1  (2.97) -4.1  (3.43)
Week 5 Number Analyzed 52 participants 54 participants
-6.2  (3.49) -5.0  (3.60)
Week 6 Number Analyzed 50 participants 51 participants
-6.5  (3.62) -5.6  (3.74)
Follow Up Number Analyzed 60 participants 61 participants
-5.6  (3.58) -5.2  (4.12)
Early Withdrawal Number Analyzed 4 participants 6 participants
0.3  (1.26) -2.0  (4.00)
9.Secondary Outcome
Title Mean HAMD-17 Total Score
Hide Description HAMD-17 is Hamilton Depression Rating Scale which has 17 questions. The HAMD-17 Total Score was calculated by summing the individual response scores over the 17 individual components of the interview. The highest possible score was 52, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. If not more than 1 response was missing, the total score was caculated as Observed Total Score * [1 + (Sum of the Maximum Score of the missing values/Sum of the Maximum Score of the non -missing values)]. There were 9 five point questions and 8 three point questions. The responses to the individual questions can have values of 0-2 (three points response) or 0-4 (five points response).
Time Frame Up to Follow-up visit (Day 53)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 62 63
Mean (Standard Deviation)
Unit of Measure: Scores on Scale
Week 1 Number Analyzed 62 participants 63 participants
21.7  (4.88) 21.2  (4.78)
Week 2 Number Analyzed 59 participants 60 participants
18.9  (5.59) 19.7  (5.36)
Week 3 Number Analyzed 54 participants 58 participants
16.5  (6.76) 17.8  (5.57)
Week 4 Number Analyzed 53 participants 57 participants
14.1  (6.10) 16.6  (5.39)
Week 5 Number Analyzed 52 participants 54 participants
12.6  (7.43) 14.8  (6.14)
Week 6 Number Analyzed 50 participants 51 participants
11.7  (7.05) 13.8  (6.50)
Follow up Number Analyzed 60 participants 61 participants
13.4  (7.34) 14.4  (7.41)
Early Withdrawal Number Analyzed 4 participants 6 participants
27.8  (5.74) 23.5  (4.18)
10.Secondary Outcome
Title Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score
Hide Description The 30 item IDS is available in two versions IDS-C and Inventory of Depressive Symptomatology self-rated (IDS-SR). To calculate the total score of IDS, 28 out of the 30 items were scored. Either weight loss or weight gain, appetite loss or appetite gain is scored because only one member of each pair is applicable to any given respondent. The standard total score is obtained by summing the ratings of 28 of the 30 items. Each of the 28 items is scored on a 0 to 3 scale (0 – the absence of pathology; 3 – severe pathology). The total scores range from 0 to 84. If more than one response was missing then the score was calculated using the formula Observed Total Score*[1+(Sum of the Maximum Score of the missing values/Sum of the Maximum Score of the non -missing values)].
Time Frame Up to Follow-up visit (Day 53)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 62 63
Mean (Standard Deviation)
Unit of Measure: Scores on Scale
Week1 Number Analyzed 62 participants 63 participants
39.7  (8.7) 39.2  (8.5)
Week 2 Number Analyzed 59 participants 60 participants
35.2  (9.8) 35.9  (9.1)
Week 3 Number Analyzed 54 participants 58 participants
30.9  (11.8) 32.4  (9.3)
Week 4 Number Analyzed 53 participants 57 participants
26.9  (10.7) 30.9  (9.8)
Week 5 Number Analyzed 52 participants 54 participants
23.4  (13.5) 27.1  (11.3)
Week 6 Number Analyzed 50 participants 51 participants
22.0  (12.8) 25.8  (12.1)
Follow-up Number Analyzed 60 participants 61 participants
25.3  (13.6) 26.6  (12.8)
Early Withdrawal Number Analyzed 4 participants 6 participants
47.0  (13.5) 41.8  (7.0)
11.Secondary Outcome
Title Mean IDS-SR Total Score
Hide Description The 30 item IDS is available in two versions IDS-SR and IDS-C. To calculate the total score of IDS, 28 out of the 30 items were scored. Either weight loss or weight gain, appetite loss or appetite gain is scored because only one member of each pair is applicable to any given respondent. The standard total score is obtained by summing the ratings of 28 of the 30 items. Each of the 28 items is scored on a 0 to 3 scale (0 – the absence of pathology; 3 – severe pathology). The total scores range from 0 to 84. If more than one response was missing then the score was calculated using the formula Observed Total Score*[1+(Sum of the Maximum Score of the missing values/Sum of the Maximum Score of the non -missing values)].
Time Frame Up to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 62 63
Mean (Standard Deviation)
Unit of Measure: Scores on Scale
Week 2 Number Analyzed 61 participants 61 participants
34.7  (11.02) 38.1  (10.79)
Week 4 Number Analyzed 56 participants 58 participants
29.2  (11.84) 32.8  (12.15)
Week 6 Number Analyzed 51 participants 53 participants
24.7  (14.98) 27.5  (13.28)
Early Termination Number Analyzed 4 participants 6 participants
48.8  (14.13) 47.0  (10.64)
12.Secondary Outcome
Title Mean Quick Inventory of Depressive Symptomatology Self Report-16 Item (QIDS-SR16) Total Score Derived From the IDS-SR (Only at Weeks 0, 2, 4 and 6)
Hide Description QIDS-SR assesses symptoms severity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criterion for major depressive disorder. It contains 16 separate items (corresponding to 16 items of the much longer IDS-SR), defining 9 DSM-IV symptom criterion domains. A total score was obtained by summing scores on each domain. The QIDS-SR total score was calculated by summing over the domain scores. The highest possible score was 27, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. Due to the small number of items, missing data was not imputed for the QIDS-SR total score.
Time Frame Weeks 0, 2, 4 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 62 63
Mean (Standard Deviation)
Unit of Measure: Scores on Scale
Week 0 Number Analyzed 62 participants 63 participants
18.0  (2.79) 17.8  (2.66)
Week 2 Number Analyzed 61 participants 61 participants
13.0  (4.22) 14.1  (3.99)
Week 4 Number Analyzed 56 participants 58 participants
10.6  (4.69) 11.8  (4.46)
Week 6 Number Analyzed 51 participants 53 participants
9.3  (5.81) 10.0  (4.75)
13.Secondary Outcome
Title Percentage of IDS-C Responders (Participants With a Reduction in Total Score of ≥50% From Randomization at Week 6/Study Exit).
Hide Description The 30 item IDS is available in two versions IDS-C and IDS-SR. To calculate the total score of IDS, 28 out of the 30 items were scored. Either item 11 or 12 (and 13 or 14) were scored. If 11 and 12 (or 13 and 14) both are scored then the item with the highest score was considered. The total score of the 28 items ranged between 0-84. A responder is a participant who has a ≥50% reduction from randomisation in the total score for IDS-C. The total score was calculated for each participant at each timepoint and the percentage change from randomisation was then calculated as ([Total score at post randomisation visit - Total score at randomisation visit]/ Total score at randomisation visit) * 100%. Responders were those with values of ≤ -50%. The change from randomization was analysed using suitable Bayesian mixed-effects model repeated measures (BMMRM) assuming missing at random (MAR).
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 50 51
Measure Type: Number
Unit of Measure: Percentage of Participants
50 41
14.Secondary Outcome
Title Percentage of IDS-C Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).
Hide Description The 30 item IDS is available in two versions IDS-C and IDS-SR. To calculate the total score of IDS, 28 out of the 30 items were scored. Either item 11 or 12 (and 13 or 14) were scored. If 11 and 12 (or 13 and 14) both are scored then the item with the highest score was considered. The total score of the 28 items ranged between 0-84. IDS-C total score was calculated for each participant at each timepoint and those participants with non-missing values for IDS-C total scores were categorised as having an IDS-C for the respective endpoint of ≤ 15 or > 15. Participants whose total score was ≤ 15 were included here.
Time Frame Week 6
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Hide Analysis Population Description
ITT Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 50 51
Measure Type: Number
Unit of Measure: Percentage of participants
38 18
15.Secondary Outcome
Title Percentage of IDS-SR Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
Hide Description The 30 item IDS is available in two versions IDS-C and IDS-SR. To calculate the total score of IDS, 28 out of the 30 items were scored. Either item 11 or 12 (and 13 or 14) were scored. If 11 and 12 (or 13 and 14) both are scored then the item with the highest score was considered. The total score of the 28 items ranged between 0-84. A responder is a participant who has a ≥50% reduction from randomisation in the total score for IDS-SR. The total score was calculated for each participant at each timepoint and the percentage change from randomisation was then calculated as ([Total score at post randomisation visit - Total score at randomisation visit]/ Total score at randomisation visit) * 100%. Responders were those with values of ≤ -50%. The change from randomization was analysed using suitable BMMRM assuming missing at random.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 51 53
Measure Type: Number
Unit of Measure: Participants
49 47
16.Secondary Outcome
Title Percentage of IDS-SR Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).
Hide Description The 30 item IDS is available in two versions IDS-C and IDS-SR. To calculate the total score of IDS, 28 out of the 30 items were scored. Either item 11 or 12 (and 13 or 14) were scored. If 11 and 12 (or 13 and 14) both are scored then the item with the highest score was considered. The total score of the 28 items ranged between 0-84. IDS-SR total score was calculated for each participant at each timepoint and those participants with non-missing values for IDS-SR total scores were categorised as having an IDS-C for the respective endpoint of ≤ 15 or > 15. Participants whose total score was ≤ 15 were included here.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 51 53
Measure Type: Number
Unit of Measure: Percentage of participants
37 19
17.Secondary Outcome
Title Percentage of QIDS-SR16 Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
Hide Description QIDS-SR assesses symptoms severity of DSM-IV diagnostic criterion for major depressive disorder. It contains 16 separate items (corresponding to 16 items of the much longer IDS-SR), defining 9 DSM-IV symptom criterion domains. A total score was obtained by summing scores on each domain.The highest possible score was 27, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. Due to the small number of items, missing data was not imputed for the QIDS-SR total score. A responder is a participant who has a ≥50% reduction from randomisation in the total score for that given endpoint. The total score was calculated for each participant at each timepoint and the percentage change from randomisation was then calculated as ([Total score at post randomisation visit - Total score at randomisation visit]/ Total score at randomisation visit) * 100%. Responders were those with values of ≤ -50%.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 51 53
Measure Type: Number
Unit of Measure: Percentage of Participants
55 45
18.Secondary Outcome
Title Percentage of QIDS-SR16 Remitters (Subjects Whose Total Score Was ≤ 5 at Week 6/Study Exit).
Hide Description QIDS-SR assesses symptoms severity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criterion for major depressive disorder. It contains 16 separate items (corresponding to 16 items of the much longer IDS-SR), defining 9 DSM-IV symptom criterion domains. A total score was obtained by summing scores on each domain. The QIDS-SR total score was calculated by summing over the domain scores. The highest possible score was 27, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. Due to the small number of items, missing data was not imputed for the QIDS-SR total score. The QIDS total score was calculated for each subject at each timepoint and those subjects with no missing value for QIDS total score was categorised as having a QIDS total score of ≤ 5 or > 5. Participants whose total score was ≤ 5 were included here.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 51 53
Measure Type: Number
Unit of Measure: Percentage of participants
31 13
19.Secondary Outcome
Title Percentage of Bech Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
Hide Description The Bech scale was extracted from the HAMD-17 and comprised of 6 items out of which 5 were 5 point questions and 1 was 3 point question. The Bech Total Score was calculated by summing the individual response scores. Due to the small number of items, missing data was not imputed for the Bech Total Score. If any of the 6 items were missing, the total score was not calculated at that visit. A responder is a participant who has a ≥50% reduction from randomisation in the total score for that given endpoint. The total score was calculated for each participant at each timepoint and the percentage change from randomisation was then calculated as ([Total score at post randomisation visit - Total score at randomisation visit]/ Total score at randomisation visit) * 100%. Responders were those with values of ≤ -50%. The change from randomization was analysed using suitable BMMRM assuming missing at random.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 51 50
Measure Type: Number
Unit of Measure: Percentage of participants
62 49
20.Secondary Outcome
Title Percentage of Bech Remitters (Participants Whose Total Score Was ≤ 4 at Week 6/Study Exit).
Hide Description The Bech scale was extracted from the HAMD-17 and comprised of 6 items out of which 5 were 5 point questions and 1 was 3 point question. The Bech Total Score was calculated by summing the individual response scores. Due to the small number of items, missing data was not imputed for the Bech Total Score. If any of the 6 items were missing, the total score was not calculated at that visit. The change from randomization was analysed using suitable BMMRM assuming missing at random MAR. The BECH total score was calculated for each subject at each timepoint and those perticipants with no missing value for BECH total score were categorised as having a BECH total score of ≤ 4 or > 4.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 51 50
Measure Type: Number
Unit of Measure: Percentage of participants
38 20
21.Secondary Outcome
Title Percentage of Participants With a Clinicians Global Impression of Improvement (CGI-I) Score of 1 ("Very Much Improved") or 2 ("Much Improved") at Weeks 1, 2, 3, 4, 5 and 6.
Hide Description The number of participantts with a CGI-I score of either 1 (“very much improved”) or 2 (much improved”) were grouped together for each timepoint. Participants with no missing CGI-I scores were categorised as having a CGI-I score of ≤ 2 or > 2.
Time Frame Weeks 1, 2, 3, 4, 5 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 62 63
Measure Type: Number
Unit of Measure: Percentage of participants
Week 1 Number Analyzed 61 participants 63 participants
10 8
Week 2 Number Analyzed 58 participants 59 participants
28 14
Week 3 Number Analyzed 51 participants 57 participants
41 39
Week 4 Number Analyzed 53 participants 56 participants
53 36
Week 5 Number Analyzed 51 participants 52 participants
61 54
Week 6 Number Analyzed 50 participants 51 participants
68 59
22.Secondary Outcome
Title Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks
Hide Description CGI-S assesses the severity of the participant's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill). The number of participants with a CGI-I score of either 1 (“very much improved”) or 2 (much improved”) were grouped together for each timepoint. Participants with no missing CGI-S scores were categorised as having a CGI-S score of ≤ 2 or > 2. The total score was calculated for each participant at each timepoint and percentage was calculated.
Time Frame Upto Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description:
Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
Overall Number of Participants Analyzed 62 63
Measure Type: Number
Unit of Measure: Percentage of participants
Week 1, Normal Number Analyzed 61 participants 63 participants
0 1.59
Week 2, Normal Number Analyzed 58 participants 59 participants
0 1.69
Week 3, Normal Number Analyzed 51 participants 57 participants
1.96 3.51
Week 4, Normal Number Analyzed 53 participants 56 participants
0 1.79
Week 5, Normal Number Analyzed 51 participants 52 participants
13.73 3.85
Week 6, Normal Number Analyzed 50 participants 51 participants
12.00 3.92
Week 1, Borderline Mentally ill Number Analyzed 61 participants 63 participants
0 1.59
Week 2, Borderline Mentally ill Number Analyzed 58 participants 59 participants
3.45 3.39
Week 3, Borderline Mentally ill Number Analyzed 51 participants 57 participants
9.80 1.75
Week 4, Borderline Mentally ill Number Analyzed 53 participants 56 participants
16.98 7.14
Week 5, Borderline Mentally ill Number Analyzed 51 participants 52 participants
17.65 17.31
Week 6, Borderline Mentally ill Number Analyzed 50 participants 51 participants
20.00 23.53
Week 1, Mildly ill Number Analyzed 61 participants 63 participants
9.84 3.17
Week 2, Mildly ill Number Analyzed 58 participants 59 participants
18.97 6.78
Week 3, Mildly ill Number Analyzed 51 participants 57 participants
29.41 24.56
Week 4, Mildly ill Number Analyzed 53 participants 56 participants
41.51 26.79
Week 5, Mildly ill Number Analyzed 51 participants 52 participants
33.33 28.85
Week 6, Mildly ill Number Analyzed 50 participants 51 participants
34.00 29.41
Week 1, Moderately ill Number Analyzed 61 participants 63 participants
40.98 46.03
Week 2, Moderately ill Number Analyzed 58 participants 59 participants
46.55 50.85
Week 3, Moderately ill Number Analyzed 51 participants 57 participants
29.41 40.35
Week 4, Moderately ill Number Analyzed 53 participants 56 participants
22.64 39.29
Week 5, Moderately ill Number Analyzed 51 participants 52 participants
17.65 25.00
Week 6, Moderately ill Number Analyzed 50 participants 51 participants
20.00 19.61
Week 1, Markedly ill Number Analyzed 61 participants 63 participants
36.07 38.10
Week 2, Markedly ill Number Analyzed 58 participants 59 participants
20.69 30.51
Week 3, Markedly ill Number Analyzed 51 participants 57 participants
21.57 22.81
Week 4, Markedly ill Number Analyzed 53 participants 56 participants
16.98 19.64
Week 5, Markedly ill Number Analyzed 51 participants 52 participants
15.69 23.08
Week 6, Markedly ill Number Analyzed 50 participants 51 participants
10.00 21.57
Week 1, Severely ill Number Analyzed 61 participants 63 participants
13.11 9.52
Week 2, Severely ill Number Analyzed 58 participants 59 participants
10.34 6.78
Week 3, Severely ill Number Analyzed 51 participants 57 participants
7.84 7.02
Week 4, Severely ill Number Analyzed 53 participants 56 participants
1.89 5.36
Week 5, Severely ill Number Analyzed 51 participants 52 participants
1.96 1.92
Week 6, Severely ill Number Analyzed 50 participants 51 participants
4.00 1.96
Time Frame Up to Follow-up visit (Day 53).
Adverse Event Reporting Description All SAEs and Non-SAEs were reported in All Subjects Population
 
Arm/Group Title Placebo GW856553 7.5 mg BID
Hide Arm/Group Description Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks. Eligible participants received GW856553 7.5 mg, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.
All-Cause Mortality
Placebo GW856553 7.5 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   0/64 (0.00%)      0/64 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo GW856553 7.5 mg BID
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/64 (1.56%)      1/64 (1.56%)    
Psychiatric disorders     
Suicidal ideation   1/64 (1.56%)  1 1/64 (1.56%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo GW856553 7.5 mg BID
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/64 (28.13%)      16/64 (25.00%)    
Gastrointestinal disorders     
Diarrhoea  7/64 (10.94%)  1/64 (1.56%) 
General disorders     
Fatigue  4/64 (6.25%)  0/64 (0.00%) 
Nervous system disorders     
Headache  9/64 (14.06%)  12/64 (18.75%) 
Psychiatric disorders     
Anxiety  2/64 (3.13%)  4/64 (6.25%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00976560     History of Changes
Other Study ID Numbers: 113009
First Submitted: September 11, 2009
First Posted: September 14, 2009
Results First Submitted: August 14, 2017
Results First Posted: November 14, 2017
Last Update Posted: November 14, 2017