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A Fixed Dose Study of 323U66 SR in the Treatment of Major Depressive Disorder (MDD)

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ClinicalTrials.gov Identifier: NCT01138007
Recruitment Status : Completed
First Posted : June 7, 2010
Results First Posted : May 6, 2013
Last Update Posted : August 10, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Depressive Disorder, Major
Interventions Drug: 323U66 SR 150 mg tablet
Drug: 323U66 SR 150 mg placebo tablet
Enrollment 572
Recruitment Details A total of 572 participants were enrolled in the study; however, 3 of these participants were mistakenly registered and were not randomized to study treatment.
Pre-assignment Details Participants who met the inclusion criteria enrolled in the 1- to 2-week Run-in Phase before entering the 8-week Treatment Phase, followed by the 2-week Follow-up Phase. In the Run-in Phase, the previous/existing prohibited medications administered were washed out, and participants' clinical symptoms were carefully monitored.
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Hide Arm/Group Description A 323U66 sustained release (SR) placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks. A 323U66 SR 150 milligram (mg) tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks. A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
Period Title: Overall Study
Started 187 190 192
Completed 165 160 144
Not Completed 22 30 48
Reason Not Completed
Adverse Event             4             12             9
Lack of Efficacy             2             0             6
Protocol Violation             2             3             2
Protocol-Defined Stopping Criteria             6             1             8
Lost to Follow-up             3             3             5
Physician Decision             0             5             3
Withdrawal by Subject             5             6             15
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg Total
Hide Arm/Group Description A 323U66 sustained release (SR) placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks. A 323U66 SR 150 milligram (mg) tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks. A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8. Total of all reporting groups
Overall Number of Baseline Participants 186 190 188 564
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 186 participants 190 participants 188 participants 564 participants
37.9  (11.09) 36.0  (10.42) 37.5  (10.96) 37.1  (10.83)
[1]
Measure Description: Baseline data were collected in members of the Full Analysis Set (FAS), consisting of all participants who took at least one dose of investigational product and provided at least one efficacy observation at a Treatment Phase visit (i.e., Week 1 or later).
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 186 participants 190 participants 188 participants 564 participants
Female
101
  54.3%
98
  51.6%
105
  55.9%
304
  53.9%
Male
85
  45.7%
92
  48.4%
83
  44.1%
260
  46.1%
[1]
Measure Description: Baseline data were collected in members of the FAS, consisting of all participants who took at least one dose of investigational product and provided at least one efficacy observation at a Treatment Phase visit (i.e., Week 1 or later).
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 186 participants 190 participants 188 participants 564 participants
Asian – Japanese Heritage 149 154 147 450
Asian – East Asian Heritage 37 36 40 113
Asian – Mixed Race 0 0 1 1
[1]
Measure Description: Baseline data were collected in members of the FAS, consisting of all participants who took at least one dose of investigational product and provided at least one efficacy observation at a Treatment Phase visit (i.e., Week 1 or later).
1.Primary Outcome
Title Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8/Withdrawal
Hide Description 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. Change from Baseline in the total score was calculated as the value at Week 8/Withdrawal minus the value at Baseline. The least squared means were estimated based on the Analysis of Covariance (ANCOVA) model including Baseline MADRS score and region as covariates.
Time Frame Baseline and Week 8/Withdrawal
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all participants who took at least one dose of investigational product and provided at least one efficacy observation at a Treatment Phase visit (i.e. Week 1 or later). Missing values were imputed using Last Observation Carried Forward (LOCF): last observed non-missing value was used to fill missing values at a later point.
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Hide Arm/Group Description:
A 323U66 sustained release (SR) placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 milligram (mg) tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
Overall Number of Participants Analyzed 186 190 188
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-13.9  (0.77) -14.4  (0.77) -12.9  (0.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 323U66 SR 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.853
Comments The p-value was estimated based on the ANCOVA model including Baseline MADRS score and region as covariates. The multiplicity was adjusted by Dunnett’s step-down procedure.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squared Mean Difference
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-2.7 to 1.7
Estimation Comments The confidence interval was estimated based on the ANCOVA model including Baseline MADRS score and region as covariates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 323U66 SR 300 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.00
Estimation Comments In the analysis plan, the second comparison of interest was not to be performed if the first comparison failed to show statistical significance.
2.Secondary Outcome
Title Change From Baseline in the MADRS Total Score at Weeks 1, 2, 4, and 6
Hide Description 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. Change from Baseline in the total score was calculated as the value at Week 1, 2, 4 and 6 minus the value at Baseline. The least squared means were estimated based on the ANCOVA model including Baseline MADRS score and region as covariates.
Time Frame Baseline; Weeks 1, 2, 4, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Missing values were imputed using LOCF. Only participants who were available at the specified time points were analyzed.
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Hide Arm/Group Description:
A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
Overall Number of Participants Analyzed 186 190 188
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 1, n=182, 187, 184 -3.4  (0.38) -2.9  (0.38) -2.7  (0.38)
Week 2, n=186, 190, 188 -6.2  (0.47) -5.0  (0.47) -5.0  (0.47)
Week 4, n=186, 190, 188 -9.2  (0.61) -8.3  (0.60) -8.2  (0.60)
Week 6, n=186, 190, 188 -11.8  (0.70) -11.7  (0.70) -11.1  (0.69)
3.Secondary Outcome
Title Change From Baseline in the MADRS Individual Item Scores at Weeks 1, 2, 4, 6, and 8
Hide Description The MADRS scale measures the depression level of a participant using 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). Scores for MADRS items 1, 2, 6, 7, and 8 were evaluated for this endpoint. Change from Baseline was calculated as the value at Week 1, 2, 4, 6, and 8 minus the value at Baseline. The least squared means were estimated based on the ANCOVA model including Baseline MADRS score of each item and region as covariates.
Time Frame Baseline; Week 1, 2, 4, 6, and 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Missing values were imputed using LOCF. Only participants who were available at the specified time points were analyzed.
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Hide Arm/Group Description:
A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
Overall Number of Participants Analyzed 186 190 188
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Item 1: Week 1, n=182, 187, 184 -0.5  (0.07) -0.3  (0.07) -0.3  (0.07)
Item 1: Week 2, n=186, 190, 188 -0.7  (0.08) -0.5  (0.08) -0.6  (0.08)
Item 1: Week 4, n=186, 190, 188 -1.0  (0.09) -0.9  (0.09) -1.0  (0.09)
Item 1: Week 6, n=186, 190, 188 -1.4  (0.10) -1.3  (0.10) -1.3  (0.10)
Item 1: Week 8, n=186, 190, 188 -1.6  (0.10) -1.6  (0.10) -1.5  (0.10)
Item 2: Week 1, n=182, 187, 184 -0.5  (0.08) -0.4  (0.08) -0.5  (0.08)
Item 2: Week 2, n=186, 190, 188 -0.8  (0.09) -0.8  (0.09) -0.7  (0.09)
Item 2: Week 4, n=186, 190, 188 -1.2  (0.10) -1.2  (0.10) -1.1  (0.10)
Item 2: Week 6, n=186, 190, 188 -1.6  (0.11) -1.6  (0.11) -1.4  (0.11)
Item 2: Week 8, n=186, 190, 188 -1.8  (0.12) -2.0  (0.12) -1.7  (0.12)
Item 6: Week 1, n=182, 187, 184 -0.3  (0.07) -0.4  (0.07) -0.4  (0.07)
Item 6: Week 2, n=186, 190, 188 -0.6  (0.08) -0.6  (0.08) -0.7  (0.08)
Item 6: Week 4, n=186, 190, 188 -1.0  (0.10) -1.1  (0.10) -1.0  (0.09)
Item 6: Week 6, n=186, 190, 188 -1.3  (0.10) -1.4  (0.10) -1.4  (0.10)
Item 6: Week 8, n=186, 190, 188 -1.5  (0.11) -1.7  (0.11) -1.6  (0.11)
Item 7: Week 1, n=182, 187, 184 -0.3  (0.08) -0.3  (0.08) -0.4  (0.08)
Item 7: Week 2, n=186, 190, 188 -0.7  (0.09) -0.6  (0.09) -0.7  (0.08)
Item 7: Week 4, n=186, 190, 188 -1.0  (0.10) -0.9  (0.10) -1.1  (0.10)
Item 7: Week 6, n=186, 190, 188 -1.4  (0.11) -1.3  (0.11) -1.4  (0.11)
Item 7: Week 8, n=186, 190, 188 -1.6  (0.11) -1.6  (0.11) -1.6  (0.11)
Item 8: Week 1, n=182, 187, 184 -0.4  (0.08) -0.3  (0.08) -0.3  (0.08)
Item 8: Week 2, n=186, 190, 188 -0.8  (0.09) -0.6  (0.09) -0.6  (0.08)
Item 8: Week 4, n=186, 190, 188 -1.1  (0.10) -0.9  (0.10) -1.0  (0.10)
Item 8: Week 6, n=186, 190, 188 -1.3  (0.11) -1.2  (0.11) -1.3  (0.11)
Item 8: Week 8, n=186, 190, 188 -1.7  (0.12) -1.7  (0.12) -1.5  (0.11)
4.Secondary Outcome
Title Number of MADRS Responders at Week 8
Hide Description 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. A MADRS responder is defined as a participant with a >=50% reduction from Baseline in the MADRS total score at Week 8.
Time Frame Baseline and Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Missing values were imputed using LOCF.
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Hide Arm/Group Description:
A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
Overall Number of Participants Analyzed 186 190 188
Measure Type: Number
Unit of Measure: participants
86 98 82
5.Secondary Outcome
Title Number of MADRS Remitters at Week 8
Hide Description 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. A MADRS remitter is defined as a participant with a MADRS total score <=11 at Week 8.
Time Frame Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Missing values were imputed using LOCF.
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Hide Arm/Group Description:
A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
Overall Number of Participants Analyzed 186 190 188
Measure Type: Number
Unit of Measure: participants
53 60 56
6.Secondary Outcome
Title Number of Clinical Global Impression-Global Improvement (CGI-GI) Responders at Week 8
Hide Description A CGI-GI assessment was performed at Week 8 (or withdrawal) in comparison with severity in depression observed at Baseline (Week 0; no actual assessment was performed at Baseline [the comparison was subjective]), by using scores from 0 to 7: 0, Not assessed; 1, Very much improved; 2, Much improved; 3, Minimally improved; 4, No change; 5, Minimally worse; 6, Much worse; 7, Very much worse. A CGI-GI responder is defined as a participant with a CGI-GI score of very much improved or much improved at Week 8.
Time Frame Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Missing values were imputed using LOCF. Only those participants who were available at Week 8 were analyzed.
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Hide Arm/Group Description:
A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
Overall Number of Participants Analyzed 177 186 173
Measure Type: Number
Unit of Measure: participants
100 103 98
7.Secondary Outcome
Title Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 4, 6, and 8
Hide Description A CGI-SI assessment was performed in terms of severity in depression, by using scores from 0 to 7: 0, Not assessed; 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. Change from Baseline in the CGI-SI score was calculated as the value at Week 1, 2, 4, 6, and 8 minus the value at Baseline. The least squared means were estimated based on the ANCOVA model including Baseline CGI-SI score and region as covariates.
Time Frame Baseline; Weeks 1, 2, 4, 6, and 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Missing values were imputed using LOCF. Only participants who were available at the specified time points were analyzed.
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Hide Arm/Group Description:
A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
Overall Number of Participants Analyzed 186 190 188
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 1, n=182, 187, 184 -0.2  (0.03) -0.1  (0.03) -0.1  (0.03)
Week 2, n=186, 190, 188 -0.3  (0.04) -0.3  (0.04) -0.2  (0.04)
Week 4, n=186, 190, 188 -0.7  (0.06) -0.5  (0.06) -0.6  (0.06)
Week 6, n=186, 190, 188 -0.9  (0.07) -0.9  (0.07) -0.9  (0.07)
Week 8, n=186, 190, 188 -1.2  (0.08) -1.2  (0.08) -1.1  (0.08)
8.Secondary Outcome
Title Change From Baseline in the Inventory of Depressive Symptomatology-Self Report (IDS-SR) Total Score at Weeks 1, 2, 4, 6, and 8
Hide Description The IDS-SR is a 30-item scale used to evaluate the severity and changes in depressive symptoms. Each item was scored from 0 (no symptoms) to 3 (greatest symptom severity). The maximum total score is 84 (0: no symptoms; 84: greatest symptom severity), as participants were asked to answer either item 11 (decreased appetite) or item 12 (increased appetite) (not both) and either item 13 (decreased weight) or item 14 (increased weight) (not both). Change from Baseline was calculated as the value at Week 1, 2, 4, 6, and 8 minus the value at Baseline. The least squared means were estimated based on the ANCOVA model including Baseline IDS-SR score and region as covariates.
Time Frame Baseline; Weeks 1, 2, 4, 6, and 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Missing values were imputed using LOCF. Only participants who were available at the specified time points were analyzed.
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Hide Arm/Group Description:
A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
Overall Number of Participants Analyzed 186 190 188
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 1, n=182, 187, 184 -4.8  (0.57) -4.2  (0.57) -3.9  (0.57)
Week 2, n=186, 190, 188 -6.9  (0.68) -6.7  (0.68) -5.8  (0.68)
Week 4, n=186, 190, 188 -9.7  (0.82) -9.3  (0.82) -8.2  (0.81)
Week 6, n=186, 190, 188 -11.5  (0.88) -12.3  (0.88) -10.9  (0.87)
Week 8, n=186, 190, 188 -13.6  (0.95) -14.5  (0.95) -12.6  (0.94)
9.Secondary Outcome
Title Change From Baseline in the IDS-SR Subscores for Energy, Pleasure, and Interest at Weeks 1, 2, 4, 6, and 8
Hide Description The IDS-SR is a 30-item scale used to evaluate the severity and changes in depressive symptoms. Each item was scored from 0 (no symptoms) to 3 (greatest symptom severity). Only five items (item 19: general interest; item 20: energy level; item 21: capacity for pleasure or enjoyment, excluding sex; item 22: interest in sex; item 30: leaden paralysis/physical energy) were evaluated for this endpoint, as a subset of the total score. The lowest possible total score and subset total score of IDS-SR are 0 and 0, and the highest possible total score and subset total score of IDS-SR are 84 and 15, respectively. Change from Baseline was calculated as the value at Week 1, 2, 4, 6, and 8 minus the value at Baseline. The least squared means were estimated based on the ANCOVA model including Baseline IDS-SR subscore and region as covariates.
Time Frame Baseline; Weeks 1, 2, 4, 6, and 8
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Hide Analysis Population Description
FAS. Missing values were imputed using LOCF. Only participants who were available at the specified time points were analyzed.
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
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A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks.
A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
Overall Number of Participants Analyzed 186 190 188
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 1, n=182, 187, 184 -1.1  (0.16) -0.9  (0.16) -0.9  (0.16)
Week 2, n=186, 190, 188 -1.3  (0.18) -1.2  (0.18) -1.3  (0.18)
Week 4, n=186, 190, 188 -2.1  (0.20) -1.8  (0.20) -2.0  (0.20)
Week 6, n=186, 190, 188 -2.5  (0.22) -2.6  (0.22) -2.5  (0.22)
Week 8, n=186, 190, 188 -2.9  (0.24) -3.1  (0.24) -3.0  (0.24)
Time Frame Serious adverse events (SAEs) and non-serious AEs were collected from the start of investigational product until the completion of the Follow-up Phase (up to 12 weeks from the start of the Run-in Phase).
Adverse Event Reporting Description SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who took at least one dose of investigational product.
 
Arm/Group Title Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Hide Arm/Group Description A 323U66 sustained release (SR) placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks. A 323U66 SR 150 milligram (mg) tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses (Dose level 1 and 2), for 8 weeks. A 323U66 SR 150 mg tablet was administered orally once in the morning, and a 323U66 SR 150 mg placebo tablet was administered orally once in the evening, with an interval of at least 8 hours between successive doses, during the first week of the Treatment Phase (Dose level 1). At Week 2, participants were up-titrated to a daily dose of 323U66 SR 300 mg, administered as a 323U66 SR 150 mg tablet twice daily, in the morning and in the evening, with an interval of at least 8 hours between successive doses (Dose level 2). Dose level 2 was maintained from Week 2 to Week 8.
All-Cause Mortality
Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/186 (1.08%)   2/190 (1.05%)   1/189 (0.53%) 
General disorders       
Pyrexia  1  0/186 (0.00%)  0/190 (0.00%)  1/189 (0.53%) 
Injury, poisoning and procedural complications       
Meniscus lesion  1  0/186 (0.00%)  1/190 (0.53%)  0/189 (0.00%) 
Musculoskeletal and connective tissue disorders       
Osteoarthritis  1  1/186 (0.54%)  0/190 (0.00%)  0/189 (0.00%) 
Nervous system disorders       
Headache  1  0/186 (0.00%)  1/190 (0.53%)  0/189 (0.00%) 
Psychiatric disorders       
Depression  1  1/186 (0.54%)  0/190 (0.00%)  0/189 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA, version 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo 323U66 SR 150 mg 323U66 SR 300 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   63/186 (33.87%)   62/190 (32.63%)   80/189 (42.33%) 
Gastrointestinal disorders       
Dry mouth  1  8/186 (4.30%)  12/190 (6.32%)  28/189 (14.81%) 
Nausea  1  15/186 (8.06%)  13/190 (6.84%)  16/189 (8.47%) 
Constipation  1  3/186 (1.61%)  8/190 (4.21%)  11/189 (5.82%) 
Infections and infestations       
Nasopharyngitis  1  35/186 (18.82%)  26/190 (13.68%)  29/189 (15.34%) 
Nervous system disorders       
Headache  1  13/186 (6.99%)  15/190 (7.89%)  19/189 (10.05%) 
Psychiatric disorders       
Insomnia  1  6/186 (3.23%)  0/190 (0.00%)  10/189 (5.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA, version 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01138007     History of Changes
Other Study ID Numbers: 113351
First Submitted: June 3, 2010
First Posted: June 7, 2010
Results First Submitted: March 7, 2013
Results First Posted: May 6, 2013
Last Update Posted: August 10, 2018