Trial Outcomes & Findings for Clinical Study to Test a New Drug to Treat Major Depression (NCT NCT00976560)

NCT ID: NCT00976560

Last Updated: 2017-11-14

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 128 participants
• Primary outcome timeframe: At Week 6
• Results posted on: 2017-11-14

Participant Flow

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]).

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.

Participant milestones

Measure	Placebo Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID 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 Study STARTED	64	64
Overall Study COMPLETED	50	51
Overall Study NOT COMPLETED	14	13

Reasons for withdrawal

Measure	Placebo Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID 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 Study Adverse Event	5	5
Overall Study Lack of Efficacy	3	5
Overall Study Protocol Violation	1	0
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	2	0
Overall Study Withdrawal by Subject	2	3

Baseline Characteristics

Clinical Study to Test a New Drug to Treat Major Depression

Baseline characteristics by cohort

Measure	Placebo n=64 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=64 Participants 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 n=128 Participants Total of all reporting groups
Age, Customized 18 to 60 years	64 Participants n=5 Participants	64 Participants n=7 Participants	128 Participants n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	39 Participants n=7 Participants	76 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	25 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	60 Participants n=5 Participants	63 Participants n=7 Participants	123 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Week 6

Population: 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.

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).

Outcome measures

Measure	Placebo n=50 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=51 Participants 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.
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.	-6.5 Scores on scale Standard Deviation 3.62	-5.6 Scores on scale Standard Deviation 3.74

SECONDARY outcome

Timeframe: 6 Weeks

Population: All Subjects Population - It comprised of all participants who receive at least one dose of study medication.

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.

Outcome measures

Measure	Placebo n=64 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=64 Participants 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.
Number of Participants With Adverse Events AEs	28 Participants	26 Participants
Number of Participants With Adverse Events SAEs	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Upto Week 6

Population: All Subjects Population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Measure	Placebo n=64 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=64 Participants 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.
Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score Week 1, Non-suicidal	55 Participants	57 Participants
Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score Week 2, Non-suicidal	54 Participants	55 Participants
Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score Week 3, Non-suicidal	49 Participants	54 Participants
Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score Week 4, Non-suicidal	50 Participants	54 Participants
Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score Week 5, Non-suicidal	49 Participants	50 Participants
Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score Week 6, Non-suicidal	50 Participants	49 Participants

SECONDARY outcome

Timeframe: Upto Week 6

Population: All Subjects Population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Measure	Placebo n=64 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=64 Participants 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.
Number of Participants With Abnormal Haematology and Clinical Chemistry Values Total Bilirubin High, Week 4	1 Participants	0 Participants
Number of Participants With Abnormal Haematology and Clinical Chemistry Values Glucose High, Week 6	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to follow-up Visit (Day 53)

Population: All Subjects Population. Only those participants with data available at the indicated time points were analyzed

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.

Outcome measures

Measure	Placebo n=64 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=64 Participants 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.
Number of Participants With Abnormal Vital Signs (Blood Pressure, Heart Rate) Low Diastolic blood pressure, Week 4	1 Participants	0 Participants
Number of Participants With Abnormal Vital Signs (Blood Pressure, Heart Rate) High Systolic blood pressure, Week 2	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to follow-up Visit (Day 53)

Population: All Subjects Population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Measure	Placebo n=64 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=64 Participants 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.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Upto Week 6

Population: 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.

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.

Outcome measures

Measure	Placebo n=62 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=63 Participants 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.
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 IL-6, Week 1, Predose	-1.06 picogram/mililitre (pg/mL) Standard Deviation 8.04	-0.27 picogram/mililitre (pg/mL) Standard Deviation 4.36
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 IL-6, Week 1, 3 hours (hrs)	-1.86 picogram/mililitre (pg/mL) Standard Deviation 9.72	-1.57 picogram/mililitre (pg/mL) Standard Deviation 4.30
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 IL-6, Week 6, Predose	-0.67 picogram/mililitre (pg/mL) Standard Deviation 11.29	-0.96 picogram/mililitre (pg/mL) Standard Deviation 5.68
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 IL-6, Week 6, 3 hrs	-0.11 picogram/mililitre (pg/mL) Standard Deviation 8.93	-0.98 picogram/mililitre (pg/mL) Standard Deviation 9.36
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 IL-6, Early Withdrawal	-7.44 picogram/mililitre (pg/mL) Standard Deviation 15.54	0.35 picogram/mililitre (pg/mL) Standard Deviation 4.52
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 TNF-alpha, Week 1, Predose	1.04 picogram/mililitre (pg/mL) Standard Deviation 9.65	-0.26 picogram/mililitre (pg/mL) Standard Deviation 1.43
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 TNF-alpha, Week 1, 3 hrs	1.41 picogram/mililitre (pg/mL) Standard Deviation 12.61	-0.65 picogram/mililitre (pg/mL) Standard Deviation 1.61
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 TNF-alpha, Week 6, Predose	3.80 picogram/mililitre (pg/mL) Standard Deviation 28.78	-0.10 picogram/mililitre (pg/mL) Standard Deviation 1.57
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 TNF-alpha, Week 6, 3 hrs	4.11 picogram/mililitre (pg/mL) Standard Deviation 29.20	-0.63 picogram/mililitre (pg/mL) Standard Deviation 1.49
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 TNF-alpha, Eary Withdrawal	0.31 picogram/mililitre (pg/mL) Standard Deviation 0.96	-1.07 picogram/mililitre (pg/mL) Standard Deviation 2.24

SECONDARY outcome

Timeframe: Up to Follow-up visit (Day 53)

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

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.

Outcome measures

Measure	Placebo n=62 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=63 Participants 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.
Change From Randomisation Bech Total Score: Bech Score Week 2	-2.5 Scores on scale Standard Deviation 2.73	-2.2 Scores on scale Standard Deviation 2.91
Change From Randomisation Bech Total Score: Bech Score Week 1	-1.2 Scores on scale Standard Deviation 2.14	-1.6 Scores on scale Standard Deviation 2.47
Change From Randomisation Bech Total Score: Bech Score Week 3	-3.9 Scores on scale Standard Deviation 3.20	-3.4 Scores on scale Standard Deviation 3.07
Change From Randomisation Bech Total Score: Bech Score Week 4	-5.1 Scores on scale Standard Deviation 2.97	-4.1 Scores on scale Standard Deviation 3.43
Change From Randomisation Bech Total Score: Bech Score Week 5	-6.2 Scores on scale Standard Deviation 3.49	-5.0 Scores on scale Standard Deviation 3.60
Change From Randomisation Bech Total Score: Bech Score Week 6	-6.5 Scores on scale Standard Deviation 3.62	-5.6 Scores on scale Standard Deviation 3.74
Change From Randomisation Bech Total Score: Bech Score Follow Up	-5.6 Scores on scale Standard Deviation 3.58	-5.2 Scores on scale Standard Deviation 4.12
Change From Randomisation Bech Total Score: Bech Score Early Withdrawal	0.3 Scores on scale Standard Deviation 1.26	-2.0 Scores on scale Standard Deviation 4.00

SECONDARY outcome

Timeframe: Up to Follow-up visit (Day 53)

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

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).

Outcome measures

Measure	Placebo n=62 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=63 Participants 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.
Mean HAMD-17 Total Score Week 2	18.9 Scores on Scale Standard Deviation 5.59	19.7 Scores on Scale Standard Deviation 5.36
Mean HAMD-17 Total Score Week 1	21.7 Scores on Scale Standard Deviation 4.88	21.2 Scores on Scale Standard Deviation 4.78
Mean HAMD-17 Total Score Week 3	16.5 Scores on Scale Standard Deviation 6.76	17.8 Scores on Scale Standard Deviation 5.57
Mean HAMD-17 Total Score Week 4	14.1 Scores on Scale Standard Deviation 6.10	16.6 Scores on Scale Standard Deviation 5.39
Mean HAMD-17 Total Score Week 5	12.6 Scores on Scale Standard Deviation 7.43	14.8 Scores on Scale Standard Deviation 6.14
Mean HAMD-17 Total Score Week 6	11.7 Scores on Scale Standard Deviation 7.05	13.8 Scores on Scale Standard Deviation 6.50
Mean HAMD-17 Total Score Follow up	13.4 Scores on Scale Standard Deviation 7.34	14.4 Scores on Scale Standard Deviation 7.41
Mean HAMD-17 Total Score Early Withdrawal	27.8 Scores on Scale Standard Deviation 5.74	23.5 Scores on Scale Standard Deviation 4.18

SECONDARY outcome

Timeframe: Up to Follow-up visit (Day 53)

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

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)].

Outcome measures

Measure	Placebo n=62 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=63 Participants 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.
Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score Week1	39.7 Scores on Scale Standard Deviation 8.7	39.2 Scores on Scale Standard Deviation 8.5
Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score Week 2	35.2 Scores on Scale Standard Deviation 9.8	35.9 Scores on Scale Standard Deviation 9.1
Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score Week 3	30.9 Scores on Scale Standard Deviation 11.8	32.4 Scores on Scale Standard Deviation 9.3
Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score Week 4	26.9 Scores on Scale Standard Deviation 10.7	30.9 Scores on Scale Standard Deviation 9.8
Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score Week 5	23.4 Scores on Scale Standard Deviation 13.5	27.1 Scores on Scale Standard Deviation 11.3
Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score Week 6	22.0 Scores on Scale Standard Deviation 12.8	25.8 Scores on Scale Standard Deviation 12.1
Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score Follow-up	25.3 Scores on Scale Standard Deviation 13.6	26.6 Scores on Scale Standard Deviation 12.8
Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score Early Withdrawal	47.0 Scores on Scale Standard Deviation 13.5	41.8 Scores on Scale Standard Deviation 7.0

SECONDARY outcome

Timeframe: Up to Week 6

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

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)].

Outcome measures

Measure	Placebo n=62 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=63 Participants 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.
Mean IDS-SR Total Score Week 2	34.7 Scores on Scale Standard Deviation 11.02	38.1 Scores on Scale Standard Deviation 10.79
Mean IDS-SR Total Score Week 4	29.2 Scores on Scale Standard Deviation 11.84	32.8 Scores on Scale Standard Deviation 12.15
Mean IDS-SR Total Score Week 6	24.7 Scores on Scale Standard Deviation 14.98	27.5 Scores on Scale Standard Deviation 13.28
Mean IDS-SR Total Score Early Termination	48.8 Scores on Scale Standard Deviation 14.13	47.0 Scores on Scale Standard Deviation 10.64

SECONDARY outcome

Timeframe: Weeks 0, 2, 4 and 6

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

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.

Outcome measures

Measure	Placebo n=62 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=63 Participants 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.
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) Week 2	13.0 Scores on Scale Standard Deviation 4.22	14.1 Scores on Scale Standard Deviation 3.99
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) Week 0	18.0 Scores on Scale Standard Deviation 2.79	17.8 Scores on Scale Standard Deviation 2.66
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) Week 4	10.6 Scores on Scale Standard Deviation 4.69	11.8 Scores on Scale Standard Deviation 4.46
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) Week 6	9.3 Scores on Scale Standard Deviation 5.81	10.0 Scores on Scale Standard Deviation 4.75

SECONDARY outcome

Timeframe: Week 6

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

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).

Outcome measures

Measure	Placebo n=50 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=51 Participants 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.
Percentage of IDS-C Responders (Participants With a Reduction in Total Score of ≥50% From Randomization at Week 6/Study Exit).	50 Percentage of Participants	41 Percentage of Participants

SECONDARY outcome

Timeframe: Week 6

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

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.

Outcome measures

Measure	Placebo n=50 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=51 Participants 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.
Percentage of IDS-C Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).	38 Percentage of participants	18 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

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

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.

Outcome measures

Measure	Placebo n=51 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=53 Participants 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.
Percentage of IDS-SR Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).	49 Participants	47 Participants

SECONDARY outcome

Timeframe: Week 6

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

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.

Outcome measures

Measure	Placebo n=51 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=53 Participants 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.
Percentage of IDS-SR Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).	37 Percentage of participants	19 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

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

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%.

Outcome measures

Measure	Placebo n=51 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=53 Participants 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.
Percentage of QIDS-SR16 Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).	55 Percentage of Participants	45 Percentage of Participants

SECONDARY outcome

Timeframe: Week 6

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

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.

Outcome measures

Measure	Placebo n=51 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=53 Participants 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.
Percentage of QIDS-SR16 Remitters (Subjects Whose Total Score Was ≤ 5 at Week 6/Study Exit).	31 Percentage of participants	13 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

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

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.

Outcome measures

Measure	Placebo n=51 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=50 Participants 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.
Percentage of Bech Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).	62 Percentage of participants	49 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

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

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.

Outcome measures

Measure	Placebo n=51 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=50 Participants 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.
Percentage of Bech Remitters (Participants Whose Total Score Was ≤ 4 at Week 6/Study Exit).	38 Percentage of participants	20 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 5 and 6

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

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.

Outcome measures

Measure	Placebo n=62 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=63 Participants 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.
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. Week 3	41 Percentage of participants	39 Percentage of participants
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. Week 1	10 Percentage of participants	8 Percentage of participants
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. Week 2	28 Percentage of participants	14 Percentage of participants
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. Week 4	53 Percentage of participants	36 Percentage of participants
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. Week 5	61 Percentage of participants	54 Percentage of participants
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. Week 6	68 Percentage of participants	59 Percentage of participants

SECONDARY outcome

Timeframe: Upto Week 6

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

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.

Outcome measures

Measure	Placebo n=62 Participants Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=63 Participants 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.
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 2, Mildly ill	18.97 Percentage of participants	6.78 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 2, Moderately ill	46.55 Percentage of participants	50.85 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 1, Normal	0 Percentage of participants	1.59 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 2, Normal	0 Percentage of participants	1.69 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 3, Normal	1.96 Percentage of participants	3.51 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 4, Normal	0 Percentage of participants	1.79 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 5, Normal	13.73 Percentage of participants	3.85 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 6, Normal	12.00 Percentage of participants	3.92 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 1, Borderline Mentally ill	0 Percentage of participants	1.59 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 2, Borderline Mentally ill	3.45 Percentage of participants	3.39 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 3, Borderline Mentally ill	9.80 Percentage of participants	1.75 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 4, Borderline Mentally ill	16.98 Percentage of participants	7.14 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 5, Borderline Mentally ill	17.65 Percentage of participants	17.31 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 6, Borderline Mentally ill	20.00 Percentage of participants	23.53 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 1, Mildly ill	9.84 Percentage of participants	3.17 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 3, Mildly ill	29.41 Percentage of participants	24.56 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 4, Mildly ill	41.51 Percentage of participants	26.79 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 5, Mildly ill	33.33 Percentage of participants	28.85 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 6, Mildly ill	34.00 Percentage of participants	29.41 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 1, Moderately ill	40.98 Percentage of participants	46.03 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 3, Moderately ill	29.41 Percentage of participants	40.35 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 4, Moderately ill	22.64 Percentage of participants	39.29 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 5, Moderately ill	17.65 Percentage of participants	25.00 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 6, Moderately ill	20.00 Percentage of participants	19.61 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 1, Markedly ill	36.07 Percentage of participants	38.10 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 2, Markedly ill	20.69 Percentage of participants	30.51 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 3, Markedly ill	21.57 Percentage of participants	22.81 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 4, Markedly ill	16.98 Percentage of participants	19.64 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 5, Markedly ill	15.69 Percentage of participants	23.08 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 6, Markedly ill	10.00 Percentage of participants	21.57 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 1, Severely ill	13.11 Percentage of participants	9.52 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 2, Severely ill	10.34 Percentage of participants	6.78 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 3, Severely ill	7.84 Percentage of participants	7.02 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 4, Severely ill	1.89 Percentage of participants	5.36 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 5, Severely ill	1.96 Percentage of participants	1.92 Percentage of participants
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks Week 6, Severely ill	4.00 Percentage of participants	1.96 Percentage of participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

GW856553 7.5 mg BID

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=64 participants at risk Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=64 participants at risk 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.
Psychiatric disorders Suicidal ideation	1.6% 1/64 • Number of events 1 • Up to Follow-up visit (Day 53). All SAEs and Non-SAEs were reported in All Subjects Population	1.6% 1/64 • Number of events 1 • Up to Follow-up visit (Day 53). All SAEs and Non-SAEs were reported in All Subjects Population

Other adverse events

Measure	Placebo n=64 participants at risk Eligible participants received matching placebo, orally, twice daily with food at morning and evening with the interval of 12 hours for 6 weeks.	GW856553 7.5 mg BID n=64 participants at risk 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.
Nervous system disorders Headache	14.1% 9/64 • Up to Follow-up visit (Day 53). All SAEs and Non-SAEs were reported in All Subjects Population	18.8% 12/64 • Up to Follow-up visit (Day 53). All SAEs and Non-SAEs were reported in All Subjects Population
Gastrointestinal disorders Diarrhoea	10.9% 7/64 • Up to Follow-up visit (Day 53). All SAEs and Non-SAEs were reported in All Subjects Population	1.6% 1/64 • Up to Follow-up visit (Day 53). All SAEs and Non-SAEs were reported in All Subjects Population
Psychiatric disorders Anxiety	3.1% 2/64 • Up to Follow-up visit (Day 53). All SAEs and Non-SAEs were reported in All Subjects Population	6.2% 4/64 • Up to Follow-up visit (Day 53). All SAEs and Non-SAEs were reported in All Subjects Population
General disorders Fatigue	6.2% 4/64 • Up to Follow-up visit (Day 53). All SAEs and Non-SAEs were reported in All Subjects Population	0.00% 0/64 • Up to Follow-up visit (Day 53). All SAEs and Non-SAEs were reported in All Subjects Population

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER