A Fixed Dose Study of 323U66 SR in the Treatment of Major... | NCT01138007

NCT01138007

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
323U66 SR 150 mg cohort	Experimental	323U66 SR 150 mg tablet is orally administered once in the morning and 323U66 SR 150 mg placebo tablet is orally administered once in the evening throughout the treatment phase.	Drug: 323U66 SR 150 mg tablet Drug: 323U66 SR 150 mg placebo tablet
323U66 SR 300 mg cohort	Experimental	323U66 SR 150 mg tablet is orally administered once in the morning and 323U66 SR 150 mg placebo tablet is orally administered once in the evening during the first week of the treatment phase. At the second week, 323U66 SR 300mg cohort is up-titrated to a daily dose of 323U66 SR 300 mg, administered as 323U66 SR 150 mg tablet twice daily in the morning and in the evening, and the same daily dose is maintained to administer until the end of the treatment phase.	Drug: 323U66 SR 150 mg tablet Drug: 323U66 SR 150 mg placebo tablet
Placebo cohort	Placebo Comparator	323U66 SR placebo tablet is orally administered twice daily throughout the treatment phase.	Drug: 323U66 SR 150 mg placebo tablet

Interventions

Name	Type	Description	Arm Group Labels	Other Names
323U66 SR 150 mg tablet	Drug	323U66 SR 150 mg tablet is orally administered once in the morning and/or once in the evening during the teatment phase.	323U66 SR 150 mg cohort

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8/Withdrawal	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.	Baseline and Week 8/Withdrawal

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in the MADRS Total Score at Weeks 1, 2, 4, and 6	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

[At the start time of the run-in phase]

Subject must have a primary diagnosis of major depressive disorder as classified by the DSM-IV-TR criteria as below (however, to exclude those accompanied by comorbid psychiatric disorders), and be showing currently a symptom of depression or depressive status: Major depressive disorder, single episode (296.2x); Major depressive disorder, recurrent (296.3x).
Subject must have a total score of >=20 on the IVRS HAM-D (17 items).
Subject must have a total score of >=25 on the IDS-SR.
Subject must have a score of >=1 on 4 out 5 items on the 5-item subscale of the IDS-SR (Item 19, 20, 21, 22 and 30), and a total score of >=7 on the 5-item subscale of the IDS-SR.
Subject must have a CGI-SI score of >=4 (i.e., Moderately ill or much worse).
Subject must have the current depressive episode's duration of >=8 weeks but <24 months.
Subject is outpatient.
Subject must show QTc <450 millisecond (msec) or <480msec with Bundle Branch Block - values based on either single ECG values or triplicate ECG averaged QTc values obtained over a brief recording period.
Subject must show a value less than twice of the upper limit of normal value range of AST (GOT) and ALT (GPT), and a value <=1.5 times of the upper limit of normal value range of both Al-P and total bilirubin (however, subject who shows >35% of direct bilirubin with a value >=1.5 times of the upper limit of normal range of total bilirubin regards eligible).
Subject must read and write at a level sufficient to provide written informed consent prior to study participation and complete study-related materials. If subject is <20 years of age at the time of giving consent, both the subject himself / herself and his / her proxy consenter must give written informed consent.

[At the start time of the treatment phase]

Subject must have a total score of >=20 of the IVRS-based HAM-D (17 items).
Subject whose IVRS HAM-D (17 items) total score has not been increased or decreased by >25% during the run-in phase.
Subject must have a total score of >=25 on the IDS-SR.
Subject must have a score of >=1 on 4 out 5 items on the 5-item subscale of the IDS-SR (Item 19, 20, 21, 22 and 30), and a total score of >=7 on the 5-item subscale of the IDS-SR.
Subject must have a CGI-SI score of >=4 (i.e., Moderately ill or much worse).

Exclusion Criteria:

[At the start time of Run-in phase (Visit 1)]

Subject has predispositions to seizure: who currently has or has a past history of seizure or seizure disorder, more than a single febrile seizure in infancy, cerebral tumour, or head / brain injury (traumatic); who has a family history of idiopathic seizure; who is diabetic patient with treating by oral hypoglycaemics or insulin; who uses drugs lowering the threshold of seizure.
Subject has a history or current diagnosis of anorexia nervosa (DSM-IV-TR 307.1) or bulimia (DSM-IV-TR 307.51).
Subject has a primary DSM-IV diagnosis of, or received treatment for, panic disorder, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), or acute stress disorder within 12 months before the start time of Run-in phase.
Subject has a DSM-IV diagnosis of schizophrenia, or other psychotic disorder(s) including bipolar disorder.
Subject has a history of or currently has manic episode(s).
Subject has any other DSM-IV axis II diagnosis that would suggest non-responsiveness to pharmacotherapy or non-compliance with the protocol (e.g., antisocial, borderline disorder or narcissistic personality disorder).
Subject starting psychotherapy (except for supportive psychotherapy not aimed at therapeutic efficacy and unlikely to affect efficacy evaluation) or a cognitive behaviour therapy within 12 weeks before start time of the run-in phase.
Subject received electroconvulsive therapy (ECT) within 24 weeks before start time of the run-in phase.
Subject took MAO inhibitors (selegiline hydrochloride) within 2 weeks before start time of the run-in phase.
Subject who has undergone treatment with a depot neuroleptic in the past.
Subject has systolic blood pressure of >=160 mmHg or diastolic pressure of >=100 mmHg.
Subject 1) is possibly pregnant, 2) is pregnant, lactating, or 3) does not agree to use contraceptive method(s) specified in the protocol to avoid pregnancy during the study (females only). Or subject wants to become pregnant during the study (females only).
Subject has a history of alcohol / substance abuse or dependence within 12 months before start time of the run-in phase and/or has a positive result in a urine test for illicit drug use at start time of the run-in phase.
Subject, who in the opinion of the investigator (or sub-investigator), poses a current serious suicidal risk or has made a suicide attempt within the past 6 months.
Subject took another investigational product for the NDA filing or for the post manufacturing / marketing approval study within 12 weeks before start time of the run-in phase.
Subject is currently participating in another clinical study in which the subject is or will be exposed to an investigational or non-investigational drug or medical device.
Subject has a history of non-responsiveness to 323U66 SR treatment in the investigational clinical trial for major depressive disorder.
Subject has a history of withdrawal from the investigational clinical trial of 323U66 SR for major depressive disorder due to any adverse event(s).
Subject has a history of hypersensitivity to 323U66 (bupropion).
Subject, who in the opinion of the investigator (or sub-investigator), has a risk of homicide.
Subject has serious cerebral disease(s).
Subject has serious physical symptom(s) (i.e., cardiac / hepatic / renal / hematopoietic disorder(s)).
Subject whose major depressive disorder is due to direct physiological effects of a general medical condition(s) (e.g. hypothyroidism, Parkinson's disease, chronic pain).
Subject is complicated by chronic hepatitis B or C being positive in test of hepatitis B surface antigen (HbsAg) or hepatitis C antibody.
Subject who is in the process of quitting smoking with nicotine formulation.
Subject has previously failed adequate (in terms of dose and duration of therapy) courses of pharmacotherapy with at least two different classes of antidepressants.
Subjects undergoing abrupt discontinuation of alcohol or sedatives.
Subject is inappropriate for participating in the study that is felt by the investigator (or sub-investigator).

[At the start time of the treatment phase]

Subject, who in the opinion of the investigator (or sub-investigator), poses a current serious suicidal risk.
Subject is inappropriate for participating in the study that is felt by the investigator (or sub-investigator).

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Aichi		470-1141	Japan
GSK Investigational Site

References Module

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
113351	Annotated Case Report Form	View IPD

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	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.
FG001	323U66 SR 150 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

323U66 SR 300 mg cohort

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.

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Placebo	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.
BG001	323U66 SR 150 mg	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.
BG002	323U66 SR 300 mg	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.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

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).

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00037.9± 11.09 BG00136.0± 10.42 BG00237.5± 10.96 BG003

Sex: Female, Male

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).

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000101 BG001

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Asian - Japanese Heritage

Title	Measurements
	BG000149 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8/Withdrawal

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.

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.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline and Week 8/Withdrawal

ID	Title	Description
OG000	Placebo	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.
OG001	323U66 SR 150 mg	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.
OG002	323U66 SR 300 mg	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.

Units	Counts
Participants	OG000186 OG001190 OG002188

Title

Denominators

Categories

Title	Measurements
	OG000-13.9± 0.77 OG001-14.4± 0.77 OG002-12.9± 0.76

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.853	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.	Least Squared Mean Difference	-0.5			2-Sided	95	-2.7	1.7			The confidence interval was estimated based on the ANCOVA model including Baseline MADRS score and region as covariates.		Superiority or Other

Secondary

Change From Baseline in the MADRS Total Score at Weeks 1, 2, 4, and 6

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.

FAS. Missing values were imputed using LOCF. Only participants who were available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline; Weeks 1, 2, 4, and 6

ID	Title	Description
OG000	Placebo	A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
OG001	323U66 SR 150 mg	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.

Secondary

Change From Baseline in the MADRS Individual Item Scores at Weeks 1, 2, 4, 6, and 8

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.

FAS. Missing values were imputed using LOCF. Only participants who were available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline; Week 1, 2, 4, 6, and 8

ID	Title	Description
OG000	Placebo	A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
OG001	323U66 SR 150 mg	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.

Secondary

Number of MADRS Responders at Week 8

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.

FAS. Missing values were imputed using LOCF.

Posted

Number

participants

Baseline and Week 8

ID	Title	Description
OG000	Placebo	A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
OG001	323U66 SR 150 mg	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.
OG002	323U66 SR 300 mg

Secondary

Number of MADRS Remitters at Week 8

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.

FAS. Missing values were imputed using LOCF.

Posted

Number

participants

Week 8

ID	Title	Description
OG000	Placebo	A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
OG001	323U66 SR 150 mg	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.
OG002	323U66 SR 300 mg	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.

Secondary

Number of Clinical Global Impression-Global Improvement (CGI-GI) Responders at Week 8

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.

FAS. Missing values were imputed using LOCF. Only those participants who were available at Week 8 were analyzed.

Posted

Number

participants

Week 8

ID	Title	Description
OG000	Placebo	A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
OG001	323U66 SR 150 mg	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.
OG002	323U66 SR 300 mg

Secondary

Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 4, 6, and 8

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.

FAS. Missing values were imputed using LOCF. Only participants who were available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline; Weeks 1, 2, 4, 6, and 8

ID	Title	Description
OG000	Placebo	A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
OG001	323U66 SR 150 mg	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.
OG002

Secondary

Change From Baseline in the Inventory of Depressive Symptomatology-Self Report (IDS-SR) Total Score at Weeks 1, 2, 4, 6, and 8

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.

FAS. Missing values were imputed using LOCF. Only participants who were available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline; Weeks 1, 2, 4, 6, and 8

ID	Title	Description
OG000	Placebo	A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
OG001	323U66 SR 150 mg	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.

Secondary

Change From Baseline in the IDS-SR Subscores for Energy, Pleasure, and Interest at Weeks 1, 2, 4, 6, and 8

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.

FAS. Missing values were imputed using LOCF. Only participants who were available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline; Weeks 1, 2, 4, 6, and 8

ID	Title	Description
OG000	Placebo	A 323U66 SR placebo tablet was administered orally twice daily, in the morning and the evening (Dose level 1 and 2), for 8 weeks.
OG001	323U66 SR 150 mg	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.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	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.	2	186	63	186
EG001	323U66 SR 150 mg	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.	2	190	62	190
EG002	323U66 SR 300 mg	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.	1	189	80	189

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pyrexia	General disorders	MedDRA, version 15.0	Systematic Assessment	EG0000 affected186 at risk EG0010 affected190 at risk EG0021 affected189 at risk
Meniscus lesion	Injury, poisoning and procedural complications	MedDRA, version 15.0	Systematic Assessment	EG0000 affected186 at risk EG0011 affected190 at risk EG0020 affected189 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA, version 15.0	Systematic Assessment	EG0001 affected186 at risk EG0010 affected190 at risk EG0020 affected189 at risk
Headache	Nervous system disorders	MedDRA, version 15.0	Systematic Assessment	EG0000 affected186 at risk EG0011 affected190 at risk EG0020 affected189 at risk
Depression	Psychiatric disorders	MedDRA, version 15.0	Systematic Assessment	EG0001 affected186 at risk EG0010 affected190 at risk EG0020 affected189 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA, version 15.0	Systematic Assessment	EG00035 affected186 at risk EG00126 affected190 at risk EG00229 affected189 at risk
Dry mouth	Gastrointestinal disorders	MedDRA, version 15.0	Systematic Assessment	EG0008 affected186 at risk EG00112 affected190 at risk EG00228 affected189 at risk
Headache	Nervous system disorders	MedDRA, version 15.0	Systematic Assessment	EG00013 affected186 at risk EG00115 affected190 at risk EG00219 affected189 at risk
Nausea	Gastrointestinal disorders	MedDRA, version 15.0	Systematic Assessment	EG00015 affected186 at risk EG00113 affected190 at risk EG00216 affected189 at risk
Constipation	Gastrointestinal disorders	MedDRA, version 15.0	Systematic Assessment	EG0003 affected186 at risk EG0018 affected190 at risk EG00211 affected189 at risk
Insomnia	Psychiatric disorders	MedDRA, version 15.0	Systematic Assessment	EG0006 affected186 at risk EG0010 affected190 at risk EG00210 affected189 at risk

ID	Term
D003865	Depressive Disorder, Major

ID	Term
D013607	Tablets

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.

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders

ID	Term
D004304	Dosage Forms
D004364	Pharmaceutical Preparations