Trial Outcomes & Findings for MDD POC Study GSK372475 Subjects Depressive Disease (NCT NCT00420641)

NCT ID: NCT00420641

Last Updated: 2018-02-05

Results Overview

The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, apparent sadness; 2, reported sadness; 3, inner tension; 4, reduced sleep; 5, reduced appetite; 6, concentration difficulties; 7, lassitude; 8, inability to feel; 9, pessimistic thoughts; 10, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score is 60; 0, no depression; 60, severely depressed. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between MADRS total score at the time point being analyzed (Week 10) to Randomization.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 492 participants
• Primary outcome timeframe: Week 0 (Randomization) and Week 10
• Results posted on: 2018-02-05

Participant Flow

The study was conducted on male and female participants, aged 18 to 64, with major depressive episodes associated with major depressive disorder (MDD), from 19 December 2006 to 24 June 2008 at 35 centers in 10 countries of Canada (4), Bulgaria (2), Croatia (5), France (4), Germany (4), Italy (2), Poland (3), Chile (3), Costa Rica (3) and India (5).

A total of 504 participants were randomized in ratio of 1:1:1 to receive placebo or GSK372475 (1.0 milligram per day [mg/day] to 1.5 mg/day) or paroxetine (20 mg/day to 30 mg/day) for 10 week double blind treatment phase.

Participant milestones

Measure	Placebo Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in Montgomery-Asberg Depression Rating Scale \[MADRS\] total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Overall Study STARTED	160	172	172
Overall Study COMPLETED	115	100	128
Overall Study NOT COMPLETED	45	72	44

Reasons for withdrawal

Measure	Placebo Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in Montgomery-Asberg Depression Rating Scale \[MADRS\] total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Overall Study Adverse Event	3	25	10
Overall Study Lost to Follow-up	2	4	2
Overall Study Protocol Violation	8	8	7
Overall Study Withdrawal by Subject	15	21	14
Overall Study Lack of Efficacy	6	5	4
Overall Study Non-compliance	7	5	4
Overall Study Other	4	4	3

Baseline Characteristics

One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.

Baseline characteristics by cohort

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Total n=493 Participants Total of all reporting groups
Age, Continuous	41.8 Years STANDARD_DEVIATION 10.89 • n=156 Participants	42.4 Years STANDARD_DEVIATION 11.64 • n=171 Participants	44.4 Years STANDARD_DEVIATION 10.90 • n=166 Participants	42.9 Years STANDARD_DEVIATION 11.19 • n=493 Participants
Sex: Female, Male Female	117 Participants n=156 Participants	117 Participants n=171 Participants	111 Participants n=166 Participants	345 Participants n=493 Participants
Sex: Female, Male Male	39 Participants n=156 Participants	54 Participants n=171 Participants	55 Participants n=166 Participants	148 Participants n=493 Participants
Race (NIH/OMB) American Indian or Alaska Native	8 Participants n=155 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	11 Participants n=171 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	11 Participants n=166 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	30 Participants n=492 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.
Race (NIH/OMB) Asian	13 Participants n=155 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	14 Participants n=171 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	12 Participants n=166 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	39 Participants n=492 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=155 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	0 Participants n=171 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	0 Participants n=166 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	1 Participants n=492 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.
Race (NIH/OMB) Black or African American	2 Participants n=155 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	0 Participants n=171 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	2 Participants n=166 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	4 Participants n=492 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.
Race (NIH/OMB) White	128 Participants n=155 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	144 Participants n=171 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	137 Participants n=166 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	409 Participants n=492 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.
Race (NIH/OMB) More than one race	3 Participants n=155 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	2 Participants n=171 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	4 Participants n=166 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	9 Participants n=492 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=155 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	0 Participants n=171 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	0 Participants n=166 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.	0 Participants n=492 Participants • One participant in the placebo arm did not have any data recorded for geographic ancestry. However the investigator commented that the participant was 'West Indian'.

PRIMARY outcome

Timeframe: Week 0 (Randomization) and Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, apparent sadness; 2, reported sadness; 3, inner tension; 4, reduced sleep; 5, reduced appetite; 6, concentration difficulties; 7, lassitude; 8, inability to feel; 9, pessimistic thoughts; 10, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score is 60; 0, no depression; 60, severely depressed. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between MADRS total score at the time point being analyzed (Week 10) to Randomization.

Outcome measures

Measure	Placebo n=117 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=100 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=130 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization at the End of the Treatment Phase in the MADRS Total Score	-16.9 Score on scale Standard Deviation 9.97	-19.0 Score on scale Standard Deviation 9.50	-20.5 Score on scale Standard Deviation 8.65

PRIMARY outcome

Timeframe: Week 0 (Randomization) and Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The HAMD is a rating instrument for evaluating severity of symptoms of depression, was completed by the participant. The rating instrument used in this study was the 17-item version (HAM-D17). The Bech scale of the HAMD-17 is composed of 6 identified items out of the 17 items rated in HAMD-17 scale. Each item is rated on either a 3-point scale (0 to 2) or a 5-point scale (0 to 4). The following symptoms were rated on a 5-point scale (0-4): depressed mood, feeling of guilt, work and interests, psychomotor retardation, and anxiety (psychic). The following symptom was rated on a 3-point scale (0-2): somatic symptoms (general). Total score ranged from 0 to 22, with 0 indicating absence of symptoms and a higher score indicating greater severity of symptoms. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between Bech total score at the time point being analyzed (Week 10) to Randomization.

Outcome measures

Measure	Placebo n=117 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=100 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=130 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Change From Randomization at the End of the Treatment Phase (Week 10) in Bech Scale (6-item of 17-item Hamilton Depression Rating [HAMD-17] Scale) Score	-6.2 Score on scale Standard Deviation 4.32	-7.2 Score on scale Standard Deviation 3.98	-7.9 Score on scale Standard Deviation 3.82

PRIMARY outcome

Timeframe: Week 0 (Randomization) and Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The IDS-CR is a standardized 30-item, clinician rated scale to assess the severity of a participant's depressive symptoms. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. In order to calculate the total score of IDS-CR, the following procedures were used: either item 11 or 12 were scored; either item 13 or 14 were scored; if both items 11 and 12 (or 13 and 14) were scored, the highest of the items was scored. The total score was obtained by adding the scores of 28 items of the 30 items. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between IDS-CR total score at the time point being analyzed (Week 10) to Randomization.

Outcome measures

Measure	Placebo n=117 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=100 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=130 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization at the End of the Treatment Phase (Week 10) in Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) Total Score	-22.3 Score on scale Standard Deviation 14.21	-25.1 Score on scale Standard Deviation 13.30	-26.8 Score on scale Standard Deviation 12.10

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The IDS-SR is a standardized 30-item, participant rated scale to assess the severity of a participant's depressive symptoms. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. In order to calculate the total score of IDS-SR, the following procedures were used: either item 11 or 12 were scored; either item 13 or 14 were scored; if both items 11 and 12 (or 13 and 14) were scored, the highest of the items was scored. The total score was obtained by adding the scores of 28 items of the 30 items. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between IDS-SR total score at the individual time points being analyzed (Week, 1, 4 and 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in IDS- Self-Rated Version (SR) Total Score Over Week 10 Week 1	-7.6 Score on scale Standard Deviation 9.05	-7.6 Score on scale Standard Deviation 9.15	-8.6 Score on scale Standard Deviation 9.96
Mean Change From Randomization in IDS- Self-Rated Version (SR) Total Score Over Week 10 Week 4	-16.8 Score on scale Standard Deviation 12.12	-15.5 Score on scale Standard Deviation 13.00	-19.1 Score on scale Standard Deviation 12.55
Mean Change From Randomization in IDS- Self-Rated Version (SR) Total Score Over Week 10 Week 10	-25.6 Score on scale Standard Deviation 16.27	-26.9 Score on scale Standard Deviation 14.73	-30.5 Score on scale Standard Deviation 13.66

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

QIDS-CR16 is a 16-item rating scale of depressive symptoms rated by the clinician. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Total score was obtained by adding scores of items of sad mood, interest, energy/fatigue, sleep disturbance, decrease/increase in appetite or weight, concentration/decision making, suicidal ideation and psychomotor agitation/retardation, the highest score on any 1 of the 4 sleep items, highest score on any 1 appetite/weight item and highest score on either of the 2 psychomotor items. Total scores range from 0-27, with a score of 0 indicating no depression and a score of 27 indicating most severe depression. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between QIDS-CR16 total score at the individual time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Clinician-rated Version (QIDS-CR16) Total Score Over Week 10 Week 1	-1.5 Score on scale Standard Deviation 2.78	-1.8 Score on scale Standard Deviation 2.76	-1.8 Score on scale Standard Deviation 3.65
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Clinician-rated Version (QIDS-CR16) Total Score Over Week 10 Week 2	-3.3 Score on scale Standard Deviation 3.67	-3.6 Score on scale Standard Deviation 4.01	-3.4 Score on scale Standard Deviation 4.70
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Clinician-rated Version (QIDS-CR16) Total Score Over Week 10 Week 3	-5.0 Score on scale Standard Deviation 4.27	-4.3 Score on scale Standard Deviation 4.24	-5.3 Score on scale Standard Deviation 4.64
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Clinician-rated Version (QIDS-CR16) Total Score Over Week 10 Week 4	-5.9 Score on scale Standard Deviation 4.75	-5.0 Score on scale Standard Deviation 4.20	-5.9 Score on scale Standard Deviation 4.61
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Clinician-rated Version (QIDS-CR16) Total Score Over Week 10 Week 5	-6.5 Score on scale Standard Deviation 4.64	-6.6 Score on scale Standard Deviation 5.09	-7.4 Score on scale Standard Deviation 4.82
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Clinician-rated Version (QIDS-CR16) Total Score Over Week 10 Week 6	-7.3 Score on scale Standard Deviation 4.88	-7.3 Score on scale Standard Deviation 5.55	-8.6 Score on scale Standard Deviation 4.92
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Clinician-rated Version (QIDS-CR16) Total Score Over Week 10 Week 8	-7.8 Score on scale Standard Deviation 5.58	-8.8 Score on scale Standard Deviation 5.07	-9.4 Score on scale Standard Deviation 5.03
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Clinician-rated Version (QIDS-CR16) Total Score Over Week 10 Week 10	-8.5 Score on scale Standard Deviation 5.31	-9.6 Score on scale Standard Deviation 4.95	-10.0 Score on scale Standard Deviation 4.85

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

QIDS-SR16 is a 16-item rating scale of depressive symptoms completed by participant. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Total score was obtained by adding scores of the items of sad mood, interest, energy/fatigue, sleep disturbance, decrease/increase in appetite or weight, concentration/decision making, suicidal ideation and psychomotor agitation/retardation, the highest score on any 1 of the 4 sleep items, highest score on any 1 appetite/weight item and highest score on either of the 2 psychomotor items. Total scores range from 0-27, with a score of 0 indicating no depression and a score of 27 indicating most severe depression. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between QIDS-SR16 total score at the individual time points being analyzed (Week 1, 4 and 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Self-rated Version (QIDS-SR16) Total Score Over Week 10 Week 1	-2.7 Score on scale Standard Deviation 3.82	-3.1 Score on scale Standard Deviation 4.00	-2.9 Score on scale Standard Deviation 4.16
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Self-rated Version (QIDS-SR16) Total Score Over Week 10 Week 4	-6.4 Score on scale Standard Deviation 5.23	-5.7 Score on scale Standard Deviation 5.31	-6.9 Score on scale Standard Deviation 5.10
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Self-rated Version (QIDS-SR16) Total Score Over Week 10 Week 10	-10.0 Score on scale Standard Deviation 6.73	-10.6 Score on scale Standard Deviation 5.64	-11.6 Score on scale Standard Deviation 5.39

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The MADRS scale measures the depression level of a participant. The items of the scale include: 1, apparent sadness; 2, reported sadness; 3, inner tension; 4, reduced sleep; 5, reduced appetite; 6, concentration difficulties; 7, lassitude; 8, inability to feel; 9, pessimistic thoughts; 10, suicidal thoughts. The item 2 (Reported Sadness) of MADRS was scored using a scale 7-point scale of 0-6, where 0 indicates absence of symptom and higher score indicates increased severity of symptom. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between MADRS Item 2 score at the time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in the MADRS Item 2 Score (Reported Sadness) Over Week 10 Week 1	-0.4 Score on scale Standard Deviation 0.84	-0.5 Score on scale Standard Deviation 0.95	-0.4 Score on scale Standard Deviation 0.97
Mean Change From Randomization in the MADRS Item 2 Score (Reported Sadness) Over Week 10 Week 2	-0.8 Score on scale Standard Deviation 1.00	-0.9 Score on scale Standard Deviation 1.15	-0.9 Score on scale Standard Deviation 1.27
Mean Change From Randomization in the MADRS Item 2 Score (Reported Sadness) Over Week 10 Week 3	-1.3 Score on scale Standard Deviation 1.26	-1.2 Score on scale Standard Deviation 1.28	-1.5 Score on scale Standard Deviation 1.28
Mean Change From Randomization in the MADRS Item 2 Score (Reported Sadness) Over Week 10 Week 4	-1.5 Score on scale Standard Deviation 1.42	-1.4 Score on scale Standard Deviation 1.23	-1.6 Score on scale Standard Deviation 1.34
Mean Change From Randomization in the MADRS Item 2 Score (Reported Sadness) Over Week 10 Week 5	-1.6 Score on scale Standard Deviation 1.43	-1.7 Score on scale Standard Deviation 1.42	-2.1 Score on scale Standard Deviation 1.28
Mean Change From Randomization in the MADRS Item 2 Score (Reported Sadness) Over Week 10 Week 6	-1.9 Score on scale Standard Deviation 1.56	-2.0 Score on scale Standard Deviation 1.53	-2.4 Score on scale Standard Deviation 1.29
Mean Change From Randomization in the MADRS Item 2 Score (Reported Sadness) Over Week 10 Week 8	-2.0 Score on scale Standard Deviation 1.43	-2.4 Score on scale Standard Deviation 1.33	-2.6 Score on scale Standard Deviation 1.34
Mean Change From Randomization in the MADRS Item 2 Score (Reported Sadness) Over Week 10 Week 10	-2.4 Score on scale Standard Deviation 1.52	-2.7 Score on scale Standard Deviation 1.36	-2.9 Score on scale Standard Deviation 1.28

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The IDS-CR is a standardized 30-item, clinician rated scale to assess the severity of a participant's depressive symptoms. The item 5 (Feeling Sad) of IDS-CR was rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in score was the difference between IDS-CR Item 5 score at the time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in the IDS-CR Scale Item 5 (Feeling Sad) Over Week 10 Week 1	-0.2 Score on scale Standard Deviation 0.61	-0.3 Score on scale Standard Deviation 0.70	-0.3 Score on scale Standard Deviation 0.75
Mean Change From Randomization in the IDS-CR Scale Item 5 (Feeling Sad) Over Week 10 Week 2	-0.5 Score on scale Standard Deviation 0.72	-0.5 Score on scale Standard Deviation 0.85	-0.6 Score on scale Standard Deviation 0.87
Mean Change From Randomization in the IDS-CR Scale Item 5 (Feeling Sad) Over Week 10 Week 3	-0.8 Score on scale Standard Deviation 0.74	-0.8 Score on scale Standard Deviation 0.91	-0.9 Score on scale Standard Deviation 0.82
Mean Change From Randomization in the IDS-CR Scale Item 5 (Feeling Sad) Over Week 10 Week 4	-0.9 Score on scale Standard Deviation 0.84	-0.8 Score on scale Standard Deviation 0.93	-1.0 Score on scale Standard Deviation 0.83
Mean Change From Randomization in the IDS-CR Scale Item 5 (Feeling Sad) Over Week 10 Week 5	-1.0 Score on scale Standard Deviation 0.84	-1.0 Score on scale Standard Deviation 1.06	-1.3 Score on scale Standard Deviation 0.86
Mean Change From Randomization in the IDS-CR Scale Item 5 (Feeling Sad) Over Week 10 Week 6	-1.1 Score on scale Standard Deviation 0.90	-1.2 Score on scale Standard Deviation 1.12	-1.5 Score on scale Standard Deviation 0.87
Mean Change From Randomization in the IDS-CR Scale Item 5 (Feeling Sad) Over Week 10 Week 8	-1.2 Score on scale Standard Deviation 0.92	-1.4 Score on scale Standard Deviation 0.98	-1.6 Score on scale Standard Deviation 0.90
Mean Change From Randomization in the IDS-CR Scale Item 5 (Feeling Sad) Over Week 10 Week 10	-1.3 Score on scale Standard Deviation 0.95	-1.5 Score on scale Standard Deviation 0.99	-1.7 Score on scale Standard Deviation 0.88

SECONDARY outcome

Timeframe: Week 0 (Randomization) and Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

HAMD-17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items of HAMD-17 are rated on a scale 3-point scale of 0-2 or a 5-point scale of 0-4 where 0 is absence of symptom and higher score indicate more severe symptom. Items rated on the 3-point scale include: insomnia early, middle, late; somatic symptoms gastrointestinal and general; genital symptoms; loss of weight; insight. Items rated on 5-point scale include: depressed mood; feelings of guilt; suicide; work and activities; retardation; agitation; anxiety psychic and somatic; hypochondriasis. Total score ranges from 0 to 52, where 0 indicates absence of symptom and higher scores indicates more severe symptoms. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between HAMD-17 total score at the time point being analyzed (Week 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization at the End of the Treatment Phase (Week 10) in the HAMD-17 Total Score Week 1	-1.9 Score on scale Standard Deviation 4.11	-1.9 Score on scale Standard Deviation 4.16	-2.3 Score on scale Standard Deviation 4.36
Mean Change From Randomization at the End of the Treatment Phase (Week 10) in the HAMD-17 Total Score Week 2	-4.3 Score on scale Standard Deviation 4.87	-4.2 Score on scale Standard Deviation 5.82	-4.8 Score on scale Standard Deviation 5.99
Mean Change From Randomization at the End of the Treatment Phase (Week 10) in the HAMD-17 Total Score Week 3	-6.6 Score on scale Standard Deviation 5.66	-4.9 Score on scale Standard Deviation 6.73	-6.9 Score on scale Standard Deviation 6.39
Mean Change From Randomization at the End of the Treatment Phase (Week 10) in the HAMD-17 Total Score Week 4	-7.7 Score on scale Standard Deviation 6.51	-6.3 Score on scale Standard Deviation 6.30	-7.9 Score on scale Standard Deviation 6.43
Mean Change From Randomization at the End of the Treatment Phase (Week 10) in the HAMD-17 Total Score Week 5	-8.5 Score on scale Standard Deviation 6.36	-7.8 Score on scale Standard Deviation 7.68	-9.9 Score on scale Standard Deviation 6.34
Mean Change From Randomization at the End of the Treatment Phase (Week 10) in the HAMD-17 Total Score Week 6	-9.9 Score on scale Standard Deviation 7.08	-9.5 Score on scale Standard Deviation 8.38	-11.6 Score on scale Standard Deviation 6.62
Mean Change From Randomization at the End of the Treatment Phase (Week 10) in the HAMD-17 Total Score Week 8	-10.4 Score on scale Standard Deviation 7.88	-11.5 Score on scale Standard Deviation 7.78	-12.7 Score on scale Standard Deviation 7.02
Mean Change From Randomization at the End of the Treatment Phase (Week 10) in the HAMD-17 Total Score Week 10	-11.5 Score on scale Standard Deviation 7.73	-12.9 Score on scale Standard Deviation 7.46	-13.9 Score on scale Standard Deviation 6.89

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 10

Population: ITT Population with OC analysis. Only those participants available at the specified time points were analyzed.

HAMD-17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, work and activities, sleep, suicide, psychomotor agitation/retardation, appetite, sexual interest, anxiety, and somatic symptoms). The items of the HAMD-17 are rated on a 3-point scale of 0-2 or a 5-point scale of 0-4. The item 1 (Depressed Mood) of HAMD-17 was rated the 5-point scale of 0-4, where 0 indicates absence of symptom and higher score indicates more severe symptom. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in the score was the difference between HAMD-17 Item 1 score at the individual time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in the HAMD-17 Scale Item 1 (Depressed Mood) Over Week 10 Week 1	-0.3 Score on scale Standard Deviation 0.69	-0.4 Score on scale Standard Deviation 0.83	-0.3 Score on scale Standard Deviation 0.79
Mean Change From Randomization in the HAMD-17 Scale Item 1 (Depressed Mood) Over Week 10 Week 2	-0.6 Score on scale Standard Deviation 0.84	-0.7 Score on scale Standard Deviation 1.03	-0.7 Score on scale Standard Deviation 0.97
Mean Change From Randomization in the HAMD-17 Scale Item 1 (Depressed Mood) Over Week 10 Week 3	-1.0 Score on scale Standard Deviation 1.06	-0.9 Score on scale Standard Deviation 1.12	-1.0 Score on scale Standard Deviation 1.01
Mean Change From Randomization in the HAMD-17 Scale Item 1 (Depressed Mood) Over Week 10 Week 4	-1.0 Score on scale Standard Deviation 1.10	-1.0 Score on scale Standard Deviation 1.10	-1.2 Score on scale Standard Deviation 1.04
Mean Change From Randomization in the HAMD-17 Scale Item 1 (Depressed Mood) Over Week 10 Week 5	-1.2 Score on scale Standard Deviation 1.11	-1.2 Score on scale Standard Deviation 1.21	-1.5 Score on scale Standard Deviation 1.06
Mean Change From Randomization in the HAMD-17 Scale Item 1 (Depressed Mood) Over Week 10 Week 6	-1.3 Score on scale Standard Deviation 1.16	-1.5 Score on scale Standard Deviation 1.31	-1.7 Score on scale Standard Deviation 1.03
Mean Change From Randomization in the HAMD-17 Scale Item 1 (Depressed Mood) Over Week 10 Week 8	-1.4 Score on scale Standard Deviation 1.18	-1.8 Score on scale Standard Deviation 1.13	-1.8 Score on scale Standard Deviation 1.06
Mean Change From Randomization in the HAMD-17 Scale Item 1 (Depressed Mood) Over Week 10 Week 10	-1.7 Score on scale Standard Deviation 1.24	-2.0 Score on scale Standard Deviation 1.18	-2.0 Score on scale Standard Deviation 1.06

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The IDS-CR and IDS-SR is a standardized 30-item scale rated by the clinician and the participant respectively to assess the severity of a participant's depressive symptoms. The 5 items of the IDS subscale include: item 19 (general interest/involvement), item 20 (energy/fatigability), item 21 (pleasure/enjoyment), item 22 (sexual interest), item 30 (Leaden paralysis/physical energy) which assessed participant's pleasure, interest and energy. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Total score ranges from 0 to 15, where 0 indicates absence of symptom and higher scores indicates more severe symptoms. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between IDS 5 Item subscale total score at the individual time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-CR 5 Item subscale, Week 1	-0.8 Score on scale Standard Deviation 2.08	-1.2 Score on scale Standard Deviation 2.32	-0.8 Score on scale Standard Deviation 2.21
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-CR 5 Item subscale, Week 3	-2.6 Score on scale Standard Deviation 3.05	-2.9 Score on scale Standard Deviation 3.13	-2.9 Score on scale Standard Deviation 3.12
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-CR 5 Item subscale, Week 4	-3.1 Score on scale Standard Deviation 3.41	-3.5 Score on scale Standard Deviation 3.13	-3.4 Score on scale Standard Deviation 3.06
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-CR 5 Item subscale, Week 5	-3.8 Score on scale Standard Deviation 3.24	-4.3 Score on scale Standard Deviation 3.60	-4.4 Score on scale Standard Deviation 3.41
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-CR 5 Item subscale, Week 6	-4.4 Score on scale Standard Deviation 3.76	-4.8 Score on scale Standard Deviation 3.81	-5.2 Score on scale Standard Deviation 3.59
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-CR 5 Item subscale, Week 8	-4.8 Score on scale Standard Deviation 3.85	-5.6 Score on scale Standard Deviation 3.56	-5.9 Score on scale Standard Deviation 3.41
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-CR 5 Item subscale, Week 10	-5.3 Score on scale Standard Deviation 3.73	-6.2 Score on scale Standard Deviation 3.42	-6.3 Score on scale Standard Deviation 3.21
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-SR 5 Item subscale, Week 1	-1.3 Score on scale Standard Deviation 2.48	-2.5 Score on scale Standard Deviation 3.10	-2.2 Score on scale Standard Deviation 3.09
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-SR 5 Item subscale, Week 2	-3.0 Score on scale Standard Deviation 4.55	-2.1 Score on scale Standard Deviation 2.97	-3.3 Score on scale Standard Deviation 4.16
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-SR 5 Item subscale, Week 3	0.0 Score on scale Standard Deviation 0.00	-3.4 Score on scale Standard Deviation 5.91	-3.7 Score on scale Standard Deviation 5.99
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-SR 5 Item subscale, Week 4	-3.5 Score on scale Standard Deviation 3.96	-4.7 Score on scale Standard Deviation 4.12	-4.9 Score on scale Standard Deviation 3.85
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-SR 5 Item subscale, Week 5	-0.7 Score on scale Standard Deviation 1.50	-5.9 Score on scale Standard Deviation 3.81	-5.0 Score on scale Standard Deviation 6.52
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-SR 5 Item subscale, Week 6	-2.8 Score on scale Standard Deviation 3.76	-1.0 Score on scale Standard Deviation 5.37	-3.3 Score on scale Standard Deviation 2.52
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-SR 5 Item subscale, Week 8	-2.5 Score on scale Standard Deviation 2.12	-7.0 Score on scale Standard Deviation 3.61	-6.3 Score on scale Standard Deviation 4.04
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-SR 5 Item subscale, Week 10	-6.2 Score on scale Standard Deviation 4.53	-7.6 Score on scale Standard Deviation 4.21	-7.9 Score on scale Standard Deviation 4.26
Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10 IDS-CR 5 Item subscale, Week 2	-1.6 Score on scale Standard Deviation 2.49	-2.5 Score on scale Standard Deviation 2.85	-2.0 Score on scale Standard Deviation 2.85

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 10

Population: ITT Population with OC analysis. Only those participants available at the specified time points were analyzed.

The CGI-S scale measures the severity of psychiatric symptoms on a 7-point scale from 1-7. The scores indicated the following: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. The score ranged from 1-7, where 1 indicated absence of symptoms and higher score indicated greater severity of symptoms. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in the score was the difference between CGI-S score at the individual time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in the Clinical Global Impression-Severity of Illness (CGI-S) Scale Over Week 10 Week 1	-0.2 Score on scale Standard Deviation 0.54	-0.3 Score on scale Standard Deviation 0.55	-0.2 Score on scale Standard Deviation 0.56
Mean Change From Randomization in the Clinical Global Impression-Severity of Illness (CGI-S) Scale Over Week 10 Week 2	-0.5 Score on scale Standard Deviation 0.70	-0.5 Score on scale Standard Deviation 0.93	-0.6 Score on scale Standard Deviation 0.88
Mean Change From Randomization in the Clinical Global Impression-Severity of Illness (CGI-S) Scale Over Week 10 Week 3	-0.8 Score on scale Standard Deviation 0.91	-0.7 Score on scale Standard Deviation 1.09	-1.1 Score on scale Standard Deviation 1.19
Mean Change From Randomization in the Clinical Global Impression-Severity of Illness (CGI-S) Scale Over Week 10 Week 4	-1.1 Score on scale Standard Deviation 1.11	-1.0 Score on scale Standard Deviation 1.20	-1.3 Score on scale Standard Deviation 1.28
Mean Change From Randomization in the Clinical Global Impression-Severity of Illness (CGI-S) Scale Over Week 10 Week 5	-1.2 Score on scale Standard Deviation 1.23	-1.4 Score on scale Standard Deviation 1.41	-1.6 Score on scale Standard Deviation 1.28
Mean Change From Randomization in the Clinical Global Impression-Severity of Illness (CGI-S) Scale Over Week 10 Week 6	-1.5 Score on scale Standard Deviation 1.30	-1.6 Score on scale Standard Deviation 1.54	-2.0 Score on scale Standard Deviation 1.36
Mean Change From Randomization in the Clinical Global Impression-Severity of Illness (CGI-S) Scale Over Week 10 Week 8	-1.7 Score on scale Standard Deviation 1.40	-1.9 Score on scale Standard Deviation 1.51	-2.2 Score on scale Standard Deviation 1.31
Mean Change From Randomization in the Clinical Global Impression-Severity of Illness (CGI-S) Scale Over Week 10 Week 10	-1.9 Score on scale Standard Deviation 1.41	-2.2 Score on scale Standard Deviation 1.54	-2.5 Score on scale Standard Deviation 1.27

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

MEI 18 item-SF questionnaire was used to measure reductions in mental energy, physical energy, and social motivation. All items use either a 7-level (0-6) or 5-level (0-4) response scale; for questions 1, 2, and 13-18, response '0' indicates lower motivation, energy and interest and responses with higher scores indicate increased motivation, energy and interest. For questions 3-12, response '0' indicates higher motivation, energy and interest and responses with higher scores indicate lower motivation, energy and interest. Items with a 5-level response scale were rescaled to 7-levels, and items were reverse-scored. Total score ranges from 0-108, where 0 indicates lower motivation, energy and interest and higher score indicates higher motivation, energy and interest. Randomization value was defined as assessment value done on Week 0. Change from Randomization in total score was difference between MEI score at individual time points being analyzed (Week 1, 4 and 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in the Motivation and Energy Inventory (MEI) 18-Item Short Form (SF) Total Score Over Week 10 Week 1	3.8 Score on scale Standard Deviation 10.18	5.7 Score on scale Standard Deviation 12.23	4.9 Score on scale Standard Deviation 12.02
Mean Change From Randomization in the Motivation and Energy Inventory (MEI) 18-Item Short Form (SF) Total Score Over Week 10 Week 4	16.1 Score on scale Standard Deviation 16.18	15.4 Score on scale Standard Deviation 17.68	18.4 Score on scale Standard Deviation 18.14
Mean Change From Randomization in the Motivation and Energy Inventory (MEI) 18-Item Short Form (SF) Total Score Over Week 10 Week 10	29.8 Score on scale Standard Deviation 23.46	31.8 Score on scale Standard Deviation 23.25	34.3 Score on scale Standard Deviation 21.07

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The CSFQ-14SF is a structured self reported questionnaire designed to measure illness- and medication-related changes in sexual functioning. It is consisting of 14 items that measure sexual activity and sexual functioning. It measures five dimensions of sexual behavior: pleasure (1 item); desire/frequency (items 2 and 3); desire/interest (items 4, 5 and 6); arousal (items 7, 8 and 9); and orgasm (items 11, 12 and 13). Items 10 and 14 are included in the total score but not in any dimension score. Items were rated on an 5 point scale from 1 to 5. Total score ranged from 14 to 70, where higher scores indicate higher sexual functioning and lower score indicate lower sexual functioning. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in the total score was the difference between CSFQ-14SF score at the individual time points being analyzed (Week 4 and 10) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in the Changes in Sexual Functioning Questionnaire 14-item Short Form (CSFQ-14SF) Over Week 10 Week 4	2.4 Score on scale Standard Deviation 5.44	3.1 Score on scale Standard Deviation 7.63	1.3 Score on scale Standard Deviation 8.08
Mean Change From Randomization in the Changes in Sexual Functioning Questionnaire 14-item Short Form (CSFQ-14SF) Over Week 10 Week 10	4.6 Score on scale Standard Deviation 8.17	6.1 Score on scale Standard Deviation 8.95	4.4 Score on scale Standard Deviation 9.30

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, apparent sadness; 2, reported sadness; 3, inner tension; 4, reduced sleep; 5, reduced appetite; 6, concentration difficulties; 7, lassitude; 8, inability to feel; 9, pessimistic thoughts; 10, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The total score ranged from 0-60, where 0 indicated no depression and 60 indicated severely depressed. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between MADRS total score at the time points being analyzed (Week 1, 2, 3, 4, 5, 6 and 8) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in the MADRS Total Score Over Week 8 Week 1	-2.9 Score on scale Standard Deviation 5.40	-2.8 Score on scale Standard Deviation 5.61	-2.8 Score on scale Standard Deviation 5.98
Mean Change From Randomization in the MADRS Total Score Over Week 8 Week 2	-6.3 Score on scale Standard Deviation 6.78	-5.7 Score on scale Standard Deviation 7.62	-6.6 Score on scale Standard Deviation 8.50
Mean Change From Randomization in the MADRS Total Score Over Week 8 Week 3	-9.7 Score on scale Standard Deviation 8.45	-7.3 Score on scale Standard Deviation 8.56	-10.1 Score on scale Standard Deviation 8.59
Mean Change From Randomization in the MADRS Total Score Over Week 8 Week 4	-11.0 Score on scale Standard Deviation 9.23	-9.5 Score on scale Standard Deviation 8.08	-11.4 Score on scale Standard Deviation 8.67
Mean Change From Randomization in the MADRS Total Score Over Week 8 Week 5	-12.0 Score on scale Standard Deviation 9.24	-11.9 Score on scale Standard Deviation 9.69	-14.9 Score on scale Standard Deviation 8.91
Mean Change From Randomization in the MADRS Total Score Over Week 8 Week 6	-14.3 Score on scale Standard Deviation 9.98	-14.5 Score on scale Standard Deviation 10.59	-17.3 Score on scale Standard Deviation 8.75
Mean Change From Randomization in the MADRS Total Score Over Week 8 Week 8	-15.1 Score on scale Standard Deviation 10.09	-17.3 Score on scale Standard Deviation 9.65	-19.1 Score on scale Standard Deviation 9.14

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The IDS-CR is a standardized 30-item, clinician rated scale to assess the severity of a participant's depressive symptoms. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. In order to calculate the total score of IDS-CR, the following procedures were used: either item 11 or 12 were scored; either item 13 or 14 were scored; if both items 11 and 12 (or 13 and 14) were scored, the highest of the items was scored. The total score was obtained by adding the scores of 28 items of the 30 items. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between IDS-CR total score at the time points being analyzed (Week 1, 2, 3, 4, 5, 6 and 8) to Randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in IDS-CR Total Score Over Week 8 Week 1	-4.4 Score on scale Standard Deviation 7.16	-4.9 Score on scale Standard Deviation 7.54	-5.1 Score on scale Standard Deviation 8.56
Mean Change From Randomization in IDS-CR Total Score Over Week 8 Week 2	-8.8 Score on scale Standard Deviation 9.03	-9.7 Score on scale Standard Deviation 10.37	-9.8 Score on scale Standard Deviation 11.55
Mean Change From Randomization in IDS-CR Total Score Over Week 8 Week 3	-12.7 Score on scale Standard Deviation 11.07	-11.2 Score on scale Standard Deviation 11.36	-14.3 Score on scale Standard Deviation 11.90
Mean Change From Randomization in IDS-CR Total Score Over Week 8 Week 4	-15.0 Score on scale Standard Deviation 12.42	-13.2 Score on scale Standard Deviation 10.97	-16.2 Score on scale Standard Deviation 11.80
Mean Change From Randomization in IDS-CR Total Score Over Week 8 Week 5	-16.9 Score on scale Standard Deviation 11.51	-16.9 Score on scale Standard Deviation 13.07	-20.1 Score on scale Standard Deviation 12.05
Mean Change From Randomization in IDS-CR Total Score Over Week 8 Week 6	-19.5 Score on scale Standard Deviation 13.11	-19.3 Score on scale Standard Deviation 14.40	-23.4 Score on scale Standard Deviation 12.60
Mean Change From Randomization in IDS-CR Total Score Over Week 8 Week 8	-20.3 Score on scale Standard Deviation 14.81	-22.8 Score on scale Standard Deviation 14.09	-25.2 Score on scale Standard Deviation 12.77

SECONDARY outcome

Timeframe: Week 0 (Randomization) up to Week 8

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The HAMD is a rating instrument for evaluating severity of symptoms of depression, was completed by the participant. Rating instrument used in this study was the 17-item version (HAM-D17). The Bech scale of the HAMD-17 is composed of 6 identified items out of the 17 items rated in HAMD-17 scale. Each item is rated on either a 3-point scale (0 to 2) or a 5-point scale (0 to 4). The following symptoms were rated on a 5-point scale (0-4): depressed mood, feeling of guilt, work and interests, psychomotor retardation, and anxiety (psychic). The following symptom was rated on a 3-point scale (0-2): somatic symptoms (general). Total score ranged from 0 to 22, with 0 indicating absence of symptoms and a higher score indicating greater severity of symptoms. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between Bech total score at the time points being analyzed (Week 1, 2, 3, 4, 5, 6 and 8) to randomization.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Mean Change From Randomization in the in Bech Scale (6-item of HAMD-17 Scale) Score Over Week 8 Week 1	-0.8 Score on scale Standard Deviation 2.06	-1.0 Score on scale Standard Deviation 2.55	-1.2 Score on scale Standard Deviation 2.52
Mean Change From Randomization in the in Bech Scale (6-item of HAMD-17 Scale) Score Over Week 8 Week 2	-2.0 Score on scale Standard Deviation 2.58	-2.2 Score on scale Standard Deviation 3.25	-2.6 Score on scale Standard Deviation 3.28
Mean Change From Randomization in the in Bech Scale (6-item of HAMD-17 Scale) Score Over Week 8 Week 3	-3.3 Score on scale Standard Deviation 3.10	-2.8 Score on scale Standard Deviation 3.82	-3.8 Score on scale Standard Deviation 3.56
Mean Change From Randomization in the in Bech Scale (6-item of HAMD-17 Scale) Score Over Week 8 Week 4	-3.9 Score on scale Standard Deviation 3.62	-3.5 Score on scale Standard Deviation 3.60	-4.3 Score on scale Standard Deviation 3.63
Mean Change From Randomization in the in Bech Scale (6-item of HAMD-17 Scale) Score Over Week 8 Week 5	-4.4 Score on scale Standard Deviation 3.42	-4.4 Score on scale Standard Deviation 4.26	-5.6 Score on scale Standard Deviation 3.61
Mean Change From Randomization in the in Bech Scale (6-item of HAMD-17 Scale) Score Over Week 8 Week 6	-5.1 Score on scale Standard Deviation 4.03	-5.4 Score on scale Standard Deviation 4.44	-6.5 Score on scale Standard Deviation 3.78
Mean Change From Randomization in the in Bech Scale (6-item of HAMD-17 Scale) Score Over Week 8 Week 8	-5.3 Score on scale Standard Deviation 4.19	-6.3 Score on scale Standard Deviation 4.10	-7.2 Score on scale Standard Deviation 3.92

SECONDARY outcome

Timeframe: Up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, apparent sadness; 2, reported sadness; 3, inner tension; 4, reduced sleep; 5, reduced appetite; 6, concentration difficulties; 7, lassitude; 8, inability to feel; 9, pessimistic thoughts; 10, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The total score ranged from 0-60, where 0 indicated no depression and 60 indicated severely depressed. Responders were defined as participants who had a >=50% reduction from randomization in MADRS total Score. Percentage change from randomization was calculated as total score at post Randomization visit minus total score at Randomization visit divided by total score at Randomization visit multiplied by 100. Remitters were defined as participants with a MADRS total score <=11.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Percentage of Responders and Remitters of MADRS Over Week 10 Responders, Week 5	35 Percentage of participants	35 Percentage of participants	51 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Responders, Week 1	3 Percentage of participants	3 Percentage of participants	4 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Responders, Week 2	8 Percentage of participants	11 Percentage of participants	13 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Responders, Week 3	20 Percentage of participants	14 Percentage of participants	25 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Responders, Week 4	29 Percentage of participants	17 Percentage of participants	35 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Responders, Week 6	40 Percentage of participants	41 Percentage of participants	63 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Responders, Week 8	44 Percentage of participants	54 Percentage of participants	72 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Responders, Week 10	55 Percentage of participants	64 Percentage of participants	81 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Remitters, Week 1	2 Percentage of participants	3 Percentage of participants	3 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Remitters, Week 2	5 Percentage of participants	7 Percentage of participants	11 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Remitters, Week 3	12 Percentage of participants	10 Percentage of participants	17 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Remitters, Week 4	18 Percentage of participants	12 Percentage of participants	22 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Remitters, Week 5	17 Percentage of participants	24 Percentage of participants	38 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Remitters, Week 6	28 Percentage of participants	33 Percentage of participants	48 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Remitters, Week 8	35 Percentage of participants	41 Percentage of participants	55 Percentage of participants
Percentage of Responders and Remitters of MADRS Over Week 10 Remitters, Week 10	45 Percentage of participants	52 Percentage of participants	68 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

IDS-CR is a standardized 30-item, clinician rated scale to assess the severity of a participant's depressive symptoms. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Total score of IDS-CR calculated as : either item 11 or 12 scored; either item 13 or 14 scored; if both items scored, the highest of the items was used. Total score was obtained by adding the scores of 28 items of the 30 items. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Responders were defined as participants who had a >=50% reduction from randomization in IDS-CR total Score. Percentage change from randomization was calculated as total score at post Randomization visit minus total score at Randomization visit divided by total score at Randomization visit multiplied by 100. Remitters were defined as participants with a IDS-CR total score <=14.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Percentage of Responders and Remitters of IDS-CR Over Week 10 Responders, Week 1	4 Percentage of participants	3 Percentage of participants	5 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Responders, Week 2	8 Percentage of participants	11 Percentage of participants	14 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Responders, Week 3	17 Percentage of participants	15 Percentage of participants	26 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Responders, Week 4	25 Percentage of participants	17 Percentage of participants	33 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Responders, Week 5	28 Percentage of participants	31 Percentage of participants	44 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Responders, Week 6	36 Percentage of participants	37 Percentage of participants	58 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Responders, Week 8	43 Percentage of participants	50 Percentage of participants	62 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Responders, Week 10	50 Percentage of participants	60 Percentage of participants	72 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Remitters, Week 1	3 Percentage of participants	1 Percentage of participants	1 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Remitters, Week 2	3 Percentage of participants	8 Percentage of participants	8 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Remitters, Week 3	8 Percentage of participants	8 Percentage of participants	13 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Remitters, Week 4	17 Percentage of participants	10 Percentage of participants	16 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Remitters, Week 5	16 Percentage of participants	18 Percentage of participants	27 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Remitters, Week 6	22 Percentage of participants	21 Percentage of participants	40 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Remitters, Week 8	28 Percentage of participants	31 Percentage of participants	44 Percentage of participants
Percentage of Responders and Remitters of IDS-CR Over Week 10 Remitters, Week 10	35 Percentage of participants	38 Percentage of participants	48 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

HAMD-17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, work and activities, sleep, suicide, psychomotor agitation/retardation, appetite, sexual interest, anxiety, and somatic symptoms). The items of the HAMD-17 are rated on a scale of 0 to 2 or 0 to 4, and the total score ranges from 0 to 52, where 0 indicates absence of symptom and higher scores indicates more severe symptoms. Responders were defined as participants who had a >=50% reduction from randomization in HAMD-17 total Score. Percentage change from randomization was calculated as total score at post Randomization visit minus total score at Randomization visit divided by total score at Randomization visit multiplied by 100. Remitters were defined as participants with a HAMD-17 total score <=7.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Responders, Week 1	3 Percentage of participants	2 Percentage of participants	4 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Responders, Week 2	8 Percentage of participants	10 Percentage of participants	14 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Responders, Week 3	16 Percentage of participants	14 Percentage of participants	25 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Responders, Week 4	25 Percentage of participants	14 Percentage of participants	32 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Responders, Week 5	29 Percentage of participants	30 Percentage of participants	42 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Responders, Week 6	36 Percentage of participants	33 Percentage of participants	54 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Responders, Week 8	41 Percentage of participants	48 Percentage of participants	62 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Responders, Week 10	51 Percentage of participants	55 Percentage of participants	72 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Remitters, Week 1	2 Percentage of participants	2 Percentage of participants	2 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Remitters, Week 2	3 Percentage of participants	5 Percentage of participants	9 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Remitters, Week 3	7 Percentage of participants	8 Percentage of participants	15 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Remitters, Week 4	17 Percentage of participants	9 Percentage of participants	16 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Remitters, Week 5	16 Percentage of participants	15 Percentage of participants	26 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Remitters, Week 6	23 Percentage of participants	20 Percentage of participants	40 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Remitters, Week 8	28 Percentage of participants	29 Percentage of participants	45 Percentage of participants
Percentage of Responders and Remitters of HAMD-17 Over Week 10 Remitters, Week 10	35 Percentage of participants	39 Percentage of participants	52 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The CGI-I scale measures the improvement of psychiatric symptoms on a 7-point scale from 1-7. The scale was rated by the clinician at every visit during the treatment phase (Week 1 through Week 10/early withdrawal) of the participant's total improvement or worsening compared with that individual's condition at the start of the study (the Randomization visit , Week 0) whether or not the change is judged to be due to drug treatment. The scores indicated the following: 1= very much improved; 2= much improved; 3= minimally improved; 4= no change; 5= minimally worse; 6= much worse; 7= very much worse. The score ranged from 1-7, where 1 indicated very much improved and higher score indicated greater severity of symptoms. Randomization value was defined as the assessment value done on Week 0. Data is reported for the percentage of participants who were much improved and very much improved.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Percentage of Participants With Clinical Global Impression - Global Improvement (CGI-I) Over Week 10 Week 1	3 Percentage of participants	4 Percentage of participants	5 Percentage of participants
Percentage of Participants With Clinical Global Impression - Global Improvement (CGI-I) Over Week 10 Week 2	12 Percentage of participants	17 Percentage of participants	20 Percentage of participants
Percentage of Participants With Clinical Global Impression - Global Improvement (CGI-I) Over Week 10 Week 3	28 Percentage of participants	27 Percentage of participants	41 Percentage of participants
Percentage of Participants With Clinical Global Impression - Global Improvement (CGI-I) Over Week 10 Week 4	40 Percentage of participants	36 Percentage of participants	49 Percentage of participants
Percentage of Participants With Clinical Global Impression - Global Improvement (CGI-I) Over Week 10 Week 5	45 Percentage of participants	48 Percentage of participants	66 Percentage of participants
Percentage of Participants With Clinical Global Impression - Global Improvement (CGI-I) Over Week 10 Week 6	59 Percentage of participants	59 Percentage of participants	77 Percentage of participants
Percentage of Participants With Clinical Global Impression - Global Improvement (CGI-I) Over Week 10 Week 8	61 Percentage of participants	69 Percentage of participants	83 Percentage of participants
Percentage of Participants With Clinical Global Impression - Global Improvement (CGI-I) Over Week 10 Week 10	62 Percentage of participants	75 Percentage of participants	82 Percentage of participants

SECONDARY outcome

Timeframe: Week 10

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Participants were asked complete the participant Satisfaction with Study Medication question at Week 10 (or early withdrawal). Satisfaction was measured using a single 7-point Likert scale from 1 to 7 where higher scores indicate greater satisfaction with study medication. A score of 1 represents very dissatisfied, whilst a score of 7 represents very satisfied. Participants were categorized as a responder if they are rated either as 6 "Satisfied" or 7 "Very Satisfied". The proportion of responders as percentage of participants based on the participant satisfaction with study medication item was defined as: number of participants with a response of 6 or 7 at the visit divided by number of participants with a satisfaction with study medication assessment at that visit (the sum of responders and non-responders) multiplied by 100.

Outcome measures

Measure	Placebo n=145 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=156 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=163 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Percentage of Participants Satisfied With Study Medication at Week 10	45 Percentage of participants	46 Percentage of participants	64 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 10

Population: ITT Population.

CSSRS is a clinician-rated scale that evaluates severity and change of suicidality by integrating both behaviour and ideation. For SB scale, participants were scored as "non-suicidal" (00), "preparatory acts or behavior communicating ideation" (01), "aborted attempt" (02), "interrupted attempt" (03) or "actual attempt" (04) based on the most severe score (4 being the most severe). On SI scale, 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), "active suicidal ideation with plan and intent" (05), based on the most severe score (5 being the most severe). For both subscales, 0 indicated absence of symptom and higher score indicated greater severity of symptom. Only those scores for which at least one participant was reported are summarized.

Outcome measures

Measure	Placebo n=156 Participants Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 Participants Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 Participants Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SB, Score 00, Week 1	150 Participants	168 Participants	166 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SB, Score 00, Week 2	144 Participants	154 Participants	154 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SB, Score 00, Week 3	139 Participants	146 Participants	151 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SB, Score 00, Week 4	139 Participants	140 Participants	148 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SB, Score 00, Week 5	129 Participants	125 Participants	141 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SB, Score 00, Week 6	132 Participants	117 Participants	136 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SB, Score 00, Week 8	116 Participants	105 Participants	133 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SB, Score 00, Week 10	120 Participants	101 Participants	130 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 00, Week 1	130 Participants	148 Participants	156 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 01, Week 1	14 Participants	17 Participants	8 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 02, Week 1	5 Participants	1 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 03, Week 1	1 Participants	1 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 04, Week 1	0 Participants	1 Participants	0 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 00, Week 2	132 Participants	138 Participants	148 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 01, Week 2	7 Participants	11 Participants	3 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 02, Week 2	2 Participants	4 Participants	2 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 03, Week 2	3 Participants	1 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 04, Week 2	0 Participants	1 Participants	0 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 00, Week 3	137 Participants	135 Participants	145 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 01, Week 3	1 Participants	8 Participants	4 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 02, Week 3	1 Participants	2 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 03, Week 3	0 Participants	1 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 00, Week 4	137 Participants	126 Participants	143 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 01, Week 4	1 Participants	10 Participants	2 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 02, Week 4	0 Participants	4 Participants	2 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 03, Week 4	2 Participants	0 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 00, Week 5	123 Participants	119 Participants	137 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 01, Week 5	3 Participants	5 Participants	2 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 02, Week 5	1 Participants	1 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 03, Week 5	3 Participants	0 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 00, Week 6	128 Participants	112 Participants	134 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 01, Week 6	3 Participants	5 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 02, Week 6	0 Participants	1 Participants	0 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 03, Week 6	1 Participants	0 Participants	2 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 00, Week 8	112 Participants	103 Participants	130 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 01, Week 8	3 Participants	2 Participants	3 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 03, Week 8	1 Participants	0 Participants	0 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 05, Week 8	0 Participants	0 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 00, Week 10	118 Participants	100 Participants	128 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 01, Week 10	2 Participants	1 Participants	1 Participants
Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10 SI, Score 02, Week 10	0 Participants	0 Participants	1 Participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 71 other events

Deaths: 0 deaths

GSK372475

Serious events: 8 serious events

Other events: 87 other events

Deaths: 1 deaths

Paroxetine

Serious events: 3 serious events

Other events: 85 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=156 participants at risk Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 participants at risk Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 participants at risk Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Psychiatric disorders Adjustment disorder with mixed disturbance of emotion and conduct	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.58% 1/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Psychiatric disorders Completed suicide	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.58% 1/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Psychiatric disorders Depression	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.60% 1/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Psychiatric disorders Major depression	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.58% 1/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Psychiatric disorders Mania	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.58% 1/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Psychiatric disorders Suicidal ideation	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.58% 1/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Infections and infestations Influenza	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.58% 1/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Infections and infestations Salpingitis	0.64% 1/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.60% 1/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
General disorders Chest pain	0.64% 1/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Hepatobiliary disorders Cholelithiasis	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.58% 1/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.60% 1/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Musculoskeletal and connective tissue disorders Synovial cyst	0.00% 0/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.58% 1/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	0.00% 0/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.

Other adverse events

Measure	Placebo n=156 participants at risk Participants received oral dose of matching placebo to capsule GSK372475/paroxetine for DL1 once daily in morning for 4 weeks of treatment period and DL2 once daily in morning for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	GSK372475 n=171 participants at risk Participants received oral dose of GSK372475 1.0 mg/day capsule at dose level 1 (DL1) once daily in morning for 4 weeks of treatment period and 1.5 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed placebo capsules to maintain blind for Taper Phase of paroxetine, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.	Paroxetine n=166 participants at risk Participants received oral dose of paroxetine 20 mg/day capsule at DL1 once daily in morning for 4 weeks of treatment period and 30 mg/day capsule once daily in morning at DL2 for remaining 6 weeks. Dose escalation was based on the investigator's judgement of participant not experiencing any troublesome adverse signs or symptoms and not meeting response criteria (\>=50% reduction from randomization in MADRS total score). Treatment Phase of study was followed by a one week Taper Phase where participants were dosed at DL1, applicable for all participants who completed 10 week double-blind treatment phase on DL2 or who withdrew prematurely after having received at least 1 week of study medication on DL2. Lorazepam (or other specified comparable sedative) was permitted as a night-time sleep aid at the recommended dosage during first 2 weeks of study starting at randomization.
Gastrointestinal disorders Dry mouth	2.6% 4/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	22.2% 38/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	9.6% 16/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Gastrointestinal disorders Nausea	7.7% 12/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	10.5% 18/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	15.7% 26/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Gastrointestinal disorders Constipation	5.1% 8/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	9.4% 16/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	8.4% 14/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Gastrointestinal disorders Diarrhoea	5.8% 9/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	5.8% 10/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	9.6% 16/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Nervous system disorders Headache	23.1% 36/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	20.5% 35/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	15.7% 26/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Nervous system disorders Somnolence	7.1% 11/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	2.3% 4/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	10.2% 17/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Nervous system disorders Dizziness	4.5% 7/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	9.9% 17/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	4.2% 7/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Psychiatric disorders Insomnia	5.1% 8/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	9.9% 17/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	4.2% 7/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Psychiatric disorders Sleep disorder	1.9% 3/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	5.8% 10/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	3.6% 6/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Infections and infestations Nasopharyngitis	5.1% 8/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	2.9% 5/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	6.6% 11/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Infections and infestations Influenza	3.8% 6/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	2.3% 4/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	5.4% 9/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Cardiac disorders Tachycardia	0.64% 1/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	7.0% 12/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	1.8% 3/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Cardiac disorders Palpitations	1.9% 3/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	5.3% 9/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	1.8% 3/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
General disorders Fatigue	5.1% 8/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	3.5% 6/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	4.8% 8/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.
Skin and subcutaneous tissue disorders Hyperhidrosis	3.2% 5/156 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	5.3% 9/171 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.	4.2% 7/166 • Adverse events were collected up to Follow-up (18 weeks). ITT Population was used.

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