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Study Of 323U66 SR In Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT00135512
Recruitment Status : Completed
First Posted : August 26, 2005
Results First Posted : February 1, 2019
Last Update Posted : February 1, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Depressive Disorder
Intervention Drug: bupropion hydrochloride
Enrollment 234
Recruitment Details From 01 December 2004 to 28 May 2007, total of 234 participants with major depressive disorder were randomized at 36 centers in Japan.
Pre-assignment Details During the screening (1 week), participants received Dose Level 1; bupropion sustained release (SR) 100 milligrams (mg) placebo tablet once daily in the morning.
Arm/Group Title Bupropion SR
Hide Arm/Group Description During treatment period, participants received Dose Level 2; bupropion SR 100 mg tablets once daily for 1 week in the morning and then the Dose Level 3; bupropion SR 100 mg tablets twice daily (BID; morning and evening) for the next 1 week of the treatment phase. If no problems were observed in tolerability with insufficient efficacy, then Dose Level 4; bupropion SR 150 mg tablets BID for 6 weeks was administered. Dose reduction back to Dose Level 3 was allowed in participants judged by the investigator to have a safety concern after dose increase to Dose Level 4 and dose adjustment between Dose Levels 3 and 4 was to be chosen optionally. If no tolerability issues were observed at Week 8 of treatment phase, the treatment continued up to a maximum of 52 weeks. One tablet was administered per dose during each dose level.
Period Title: Overall Study
Started 234
Completed 111
Not Completed 123
Reason Not Completed
Adverse Event             56
Lack of Efficacy             25
Other             42
Arm/Group Title Bupropion SR
Hide Arm/Group Description During treatment period, participants received Dose Level 2; bupropion SR 100 mg tablets once daily for 1 week in the morning and then the Dose Level 3; bupropion SR 100 mg tablets BID; morning and evening for the next 1 week of the treatment phase. If no problems were observed in tolerability with insufficient efficacy, then Dose Level 4; bupropion SR 150 mg tablets BID for 6 weeks. Dose reduction back to Dose Level 3 was allowed in participants judged by the investigator to have a safety concern after dose increase to Dose Level 4 and dose adjustment between Dose Levels 3 and 4 was to be chosen optionally. If no tolerability issues were observed at Week 8 of treatment phase, the treatment continued up to a maximum of 52 weeks. One tablet was administered per dose during each dose level.
Overall Number of Baseline Participants 232
Hide Baseline Analysis Population Description
Full analysis set was defined as all participants who entered treatment phase, except those who met any of the following criteria: did not satisfy the eligible disease criterion, received no dose of the investigational product and no observation data on post-treatment efficacy.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 232 participants
36.1  (10.13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 232 participants
Female
101
  43.5%
Male
131
  56.5%
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 232 participants
American Indian or Alaska Native
0
   0.0%
Asian
231
  99.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
0
   0.0%
More than one race
0
   0.0%
Unknown or Not Reported
1
   0.4%
[1]
Measure Description: Race data for 231 participants is presented and race for 1 participant was unknown.
1.Primary Outcome
Title Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8 in Observed Cases
Hide Description The MADRS is a semi-structured interview rating scale for depression that assesses 10 symptoms. The scale is composed of 10 questions (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) with a fixed 7 point scale (0, no depression; 60, severely depressed). Total score ranges from 0-60. A higher score indicates more depressive symptoms. MADRS Response was defined as a reduction in MADRS score from Baseline. Change from Baseline in the total score was calculated as the value at Week 8 minus the value at Baseline. Baseline was defined as value at Week 0.
Time Frame Baseline (Week 0) and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was used.
Arm/Group Title Bupropion SR
Hide Arm/Group Description:
During treatment period, participants received Dose Level 2; bupropion SR 100 mg tablets once daily for 1 week in the morning and then the Dose Level 3; bupropion SR 100 mg tablets BID; morning and evening for the next 1 week of the treatment phase. If no problems were observed in tolerability with insufficient efficacy, then Dose Level 4; bupropion SR 150 mg tablets BID for 6 weeks. Dose reduction back to Dose Level 3 was allowed in participants judged by the investigator to have a safety concern after dose increase to Dose Level 4 and dose adjustment between Dose Levels 3 and 4 was to be chosen optionally. If no tolerability issues were observed at Week 8 of treatment phase, the treatment continued up to a maximum of 52 weeks. One tablet was administered per dose during each dose level.
Overall Number of Participants Analyzed 232
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-16.8  (8.43)
2.Secondary Outcome
Title Change From Baseline in the MADRS Total Score at Week 52 in Observed Cases
Hide Description The MADRS is a semi-structured interview rating scale for depression that assesses 10 symptoms. The scale is composed of 10 questions (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) with a fixed 7 point scale (0, no depression; 60, severely depressed). Total score ranges from 0-60. A higher score indicates more depressive symptoms. MADRS Response was defined as a reduction in MADRS score from Baseline. Change from Baseline in the total score was calculated as the value at Week 52 minus the value at Baseline. Baseline was defined as value at Week 0.
Time Frame Baseline (Week 0) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was used.
Arm/Group Title Bupropion SR
Hide Arm/Group Description:
During treatment period, participants received Dose Level 2; bupropion SR 100 mg tablets once daily for 1 week in the morning and then the Dose Level 3; bupropion SR 100 mg tablets BID; morning and evening for the next 1 week of the treatment phase. If no problems were observed in tolerability with insufficient efficacy, then Dose Level 4; bupropion SR 150 mg tablets BID for 6 weeks. Dose reduction back to Dose Level 3 was allowed in participants judged by the investigator to have a safety concern after dose increase to Dose Level 4 and dose adjustment between Dose Levels 3 and 4 was to be chosen optionally. If no tolerability issues were observed at Week 8 of treatment phase, the treatment continued up to a maximum of 52 weeks. One tablet was administered per dose during each dose level.
Overall Number of Participants Analyzed 232
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-24.6  (8.34)
3.Secondary Outcome
Title Change From Baseline in the Hamilton Depression Rating Scale (HAM-D; 17 Items) Total Score at Weeks 8 and 52 in Observed Cases
Hide Description Each item was rated on either a 3-point scale (0 to 2; 8 questions) or a 5-point scale (0 to 4; 9 questions), with higher scores indicating greater symptom severity. The total score was calculated by summing the individual response scores. Total score ranged from 0 to 52. The following symptoms were rated on a 5-point scale (0-4): depressed mood, low self-esteem (guilt), suicidal thoughts, work and interests, psychomotor retardation, psychomotor agitation, anxiety (psychic), anxiety (somatic), and hypochondriasis (somatization). The following symptoms were rated on a 3-point scale (0-2): insomnia (initial), insomnia (middle), insomnia (late), gastrointestinal symptoms (appetite), somatic symptoms (general), sexual disturbances, insight, and weight loss. Change from Baseline in the total score was calculated as the score at Week 8 and 52 minus the score at Baseline. Baseline was defined as value at Week 0.
Time Frame Baseline (Week 0) and Week 8, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was used.
Arm/Group Title Bupropion SR
Hide Arm/Group Description:
During treatment period, participants received Dose Level 2; bupropion SR 100 mg tablets once daily for 1 week in the morning and then the Dose Level 3; bupropion SR 100 mg tablets BID; morning and evening for the next 1 week of the treatment phase. If no problems were observed in tolerability with insufficient efficacy, then Dose Level 4; bupropion SR 150 mg tablets BID for 6 weeks. Dose reduction back to Dose Level 3 was allowed in participants judged by the investigator to have a safety concern after dose increase to Dose Level 4 and dose adjustment between Dose Levels 3 and 4 was to be chosen optionally. If no tolerability issues were observed at Week 8 of treatment phase, the treatment continued up to a maximum of 52 weeks. One tablet was administered per dose during each dose level.
Overall Number of Participants Analyzed 232
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 8 -11.8  (6.06)
Week 52 -17.3  (6.38)
4.Secondary Outcome
Title Percentage of Participants Who Were Clinical Global Impression Global Improvement (CGI-I) Responders at Weeks 8 and 52 in Observed Cases
Hide Description The CGI-I scale was used to rate improvement in the participant’s condition (benefits) since Baseline using the following 7-point scale: 1: very much improved, 2: much improved, 3: minimally improved, 4: not changed, 5: minimally worse, 6: much worse and 7: very much worse. A responder was defined as “very much improved” or “much improved”.
Time Frame Week 8, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was used.
Arm/Group Title Bupropion SR
Hide Arm/Group Description:
During treatment period, participants received Dose Level 2; bupropion SR 100 mg tablets once daily for 1 week in the morning and then the Dose Level 3; bupropion SR 100 mg tablets BID; morning and evening for the next 1 week of the treatment phase. If no problems were observed in tolerability with insufficient efficacy, then Dose Level 4; bupropion SR 150 mg tablets BID for 6 weeks. Dose reduction back to Dose Level 3 was allowed in participants judged by the investigator to have a safety concern after dose increase to Dose Level 4 and dose adjustment between Dose Levels 3 and 4 was to be chosen optionally. If no tolerability issues were observed at Week 8 of treatment phase, the treatment continued up to a maximum of 52 weeks. One tablet was administered per dose during each dose level.
Overall Number of Participants Analyzed 232
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participant
Week 8
68.7
(61.0 to 75.6)
Week 52
89.0
(81.6 to 94.2)
5.Secondary Outcome
Title Change From Baseline in CGI Severity of Illness (CGI-SI) at Weeks 8 and 52 in Observed Cases
Hide Description CGI-SI was assessed on an 8-grade scale: 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 and 7, among the most extremely ill. Higher score indicated severely ill. CGI-SI was assessed by the investigator. The change from Baseline in CGI-SI score was calculated as the score at Weeks 8 and 52 minus the score at Baseline. Baseline was defined as value at Week 0.
Time Frame Baseline (Week 0) and Week 8, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was used.
Arm/Group Title Bupropion SR
Hide Arm/Group Description:
During treatment period, participants received Dose Level 2; bupropion SR 100 mg tablets once daily for 1 week in the morning and then the Dose Level 3; bupropion SR 100 mg tablets BID; morning and evening for the next 1 week of the treatment phase. If no problems were observed in tolerability with insufficient efficacy, then Dose Level 4; bupropion SR 150 mg tablets BID for 6 weeks. Dose reduction back to Dose Level 3 was allowed in participants judged by the investigator to have a safety concern after dose increase to Dose Level 4 and dose adjustment between Dose Levels 3 and 4 was to be chosen optionally. If no tolerability issues were observed at Week 8 of treatment phase, the treatment continued up to a maximum of 52 weeks. One tablet was administered per dose during each dose level.
Overall Number of Participants Analyzed 232
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 8 -1.3  (0.98)
Week 52 -2.3  (1.16)
6.Secondary Outcome
Title Change From Baseline in the Sheehan Disability Scale (SDISS) Total Score at Weeks 8 and 52 in Observed Cases
Hide Description SDISS is a composite of 3 self-rated items designed to measure the extent to which 3 major sectors in the participant's life are impaired by panic, anxiety, phobic, or depressive symptoms. The participant rates the extent to which his or her (1) work, (2) social life or leisure activities, and (3) home life or family responsibilities were impaired by his or her symptoms on a 10-point visual analog scale. To get a total score, 3 individual scores were added and the total score ranged from "0 = unimpaired" to "30 = highly impaired". Higher scores indicate worsening. The change from Baseline in SDISS total score was calculated as the score at Weeks 8 and 52 minus the score at Baseline. Baseline was defined as value at Week 0.
Time Frame Baseline (Week 0) and Week 8, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was used.
Arm/Group Title Bupropion SR
Hide Arm/Group Description:
During treatment period, participants received Dose Level 2; bupropion SR 100 mg tablets once daily for 1 week in the morning and then the Dose Level 3; bupropion SR 100 mg tablets BID; morning and evening for the next 1 week of the treatment phase. If no problems were observed in tolerability with insufficient efficacy, then Dose Level 4; bupropion SR 150 mg tablets BID for 6 weeks. Dose reduction back to Dose Level 3 was allowed in participants judged by the investigator to have a safety concern after dose increase to Dose Level 4 and dose adjustment between Dose Levels 3 and 4 was to be chosen optionally. If no tolerability issues were observed at Week 8 of treatment phase, the treatment continued up to a maximum of 52 weeks. One tablet was administered per dose during each dose level.
Overall Number of Participants Analyzed 232
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 8 -5.0  (5.54)
Week 52 -9.7  (7.31)
7.Secondary Outcome
Title Change From Baseline in the Motivation Energy Inventory Short Form (MEI-SF) Total Score at Weeks 8 and 52 in Observed Cases
Hide Description The MEI-SF (18 questions) was used to measure the reductions in mental energy, physical energy and social motivation. Minimal clinically important differences were estimated as 0.5 standard deviations or 7.5 points. All items use either a 7-level (0 to 6) or 5-level (0 to 4) response scale; items with a 5-level response scale were rescaled to 7-levels and items were reverse-scored as necessary such that higher scores represent higher health-related quality of life (HRQoL) total score ranges from 0 to 108 points. Recall period was past week prior to administration. The change from Baseline in MEI-SF total score was calculated as the score at Weeks 8 and 52 minus the score at Baseline. Baseline was defined as value at Week 0.
Time Frame Baseline (Week 0) and Week 8, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set was used.
Arm/Group Title Bupropion SR
Hide Arm/Group Description:
During treatment period, participants received Dose Level 2; bupropion SR 100 mg tablets once daily for 1 week in the morning and then the Dose Level 3; bupropion SR 100 mg tablets BID; morning and evening for the next 1 week of the treatment phase. If no problems were observed in tolerability with insufficient efficacy, then Dose Level 4; bupropion SR 150 mg tablets BID for 6 weeks. Dose reduction back to Dose Level 3 was allowed in participants judged by the investigator to have a safety concern after dose increase to Dose Level 4 and dose adjustment between Dose Levels 3 and 4 was to be chosen optionally. If no tolerability issues were observed at Week 8 of treatment phase, the treatment continued up to a maximum of 52 weeks. One tablet was administered per dose during each dose level.
Overall Number of Participants Analyzed 232
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 8 15.2  (15.51)
Week 52 26.7  (20.54)
Time Frame All adverse events (AE) and serious adverse events (SAE) were reported up to Week 52.
Adverse Event Reporting Description All participants who had participated in the study and had received at least 1 dose of the investigational product were included in the safety population and were used for reporting non-SAE and SAE.
 
Arm/Group Title Bupropion SR
Hide Arm/Group Description During treatment period, participants received Dose Level 2; bupropion SR 100 mg tablets once daily for 1 week in the morning and then the Dose Level 3; bupropion SR 100 mg tablets BID; morning and evening for the next 1 week of the treatment phase. If no problems were observed in tolerability with insufficient efficacy, then Dose Level 4; bupropion SR 150 mg tablets BID for 6 weeks. Dose reduction back to Dose Level 3 was allowed in participants judged by the investigator to have a safety concern after dose increase to Dose Level 4 and dose adjustment between Dose Levels 3 and 4 was to be chosen optionally. If no tolerability issues were observed at Week 8 of treatment phase, the treatment continued up to a maximum of 52 weeks. One tablet was administered per dose during each dose level.
All-Cause Mortality
Bupropion SR
Affected / at Risk (%)
Total   1/233 (0.43%) 
Show Serious Adverse Events Hide Serious Adverse Events
Bupropion SR
Affected / at Risk (%)
Total   14/233 (6.01%) 
General disorders   
Death  1  1/233 (0.43%) 
Hepatobiliary disorders   
Hepatic function abnormal  1  1/233 (0.43%) 
Infections and infestations   
Gastroenteritis bacterial  1  1/233 (0.43%) 
Injury, poisoning and procedural complications   
Back injury  1  1/233 (0.43%) 
Intentional misuse  1  1/233 (0.43%) 
Tibia fracture  1  1/233 (0.43%) 
Musculoskeletal and connective tissue disorders   
Spinal osteoarthritis  1  1/233 (0.43%) 
Nervous system disorders   
Grand mal convulsion  1  1/233 (0.43%) 
Tremor  1  1/233 (0.43%) 
Pregnancy, puerperium and perinatal conditions   
Abortion spontaneous  1  1/233 (0.43%) 
Psychiatric disorders   
Depression  1  3/233 (1.29%) 
Suicidal ideation  1  1/233 (0.43%) 
Reproductive system and breast disorders   
Genital haemorrhage  1  1/233 (0.43%) 
Skin and subcutaneous tissue disorders   
Drug eruption  1  1/233 (0.43%) 
1
Term from vocabulary, MedDRA version
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bupropion SR
Affected / at Risk (%)
Total   210/233 (90.13%) 
Gastrointestinal disorders   
Nausea  1  26/233 (11.16%) 
Abdominal pain upper  1  14/233 (6.01%) 
Constipation  1  14/233 (6.01%) 
Diarrhoea  1  14/233 (6.01%) 
Stomach discomfort  1  14/233 (6.01%) 
General disorders   
Thirst  1  42/233 (18.03%) 
Infections and infestations   
Nasopharyngitis  1  85/233 (36.48%) 
Nervous system disorders   
Headache  1  22/233 (9.44%) 
Dizziness  1  16/233 (6.87%) 
Psychiatric disorders   
Depression  1  17/233 (7.30%) 
1
Term from vocabulary, MedDRA version
Indicates events were collected by systematic assessment
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: NCT00135512     History of Changes
Other Study ID Numbers: AK1102364
First Submitted: August 24, 2005
First Posted: August 26, 2005
Results First Submitted: June 22, 2017
Results First Posted: February 1, 2019
Last Update Posted: February 1, 2019