Depressive Disorder
Conditions
Keywords
Immediate-release formulation of paroxetine (paroxetine IR), HAM-D (17 items), Controlled-release formulation of paroxetine (paroxetine CR)
Brief summary
This is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy of controlled-release (CR) formulation of paroxetine orally administered to patients with major depressive disorder (MDD) at a dose level in the range of 25 - 50 mg/day (initial dose level, 12.5 or 25 mg/day) once daily after evening meal for 8 weeks based on the decrease in HAM-D (Hamilton Depression Rating Scale) total score, to evaluate the safety based on adverse events, laboratory data and vital signs, and to describe the efficacy and safety of immediate release (IR) formulation of paroxetine.
Interventions
DRUGparoxetine IR 10mg tablet
1 or 2 tablets once a day
DRUGparoxetine IR 20mg tablet
1 tablet once a day
DRUGmatched placebo to paroxetine IR 10mg or 20mg
1 or 2 tablets once a day
DRUGParoxetine CR 12.5mg tablet
1 or 2 tablets once a day
DRUGParoxetine CR 25mg tablet
1 or 2 tablets once a day
DRUGmatched placebo to paroxetine CR 12.5mg or 25mg
1 or 2 tablets once a day
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\<at the start of placebo run-in phase\> Only the patients who meet all of the following conditions at Week -1 (at the start of placebo run-in phase) will be enrolled in this study. The hospitalization status will be no object. and Gender: No object. * Target disease: Patients diagnosed as having one of the following depressive disorders based on DSM-IV-TR classification in conjunction with M.I.N.I. (The Mini International Neuropsychiatric Interview, Japanese version 5.0.0. \[2003\]) and showing currently a symptom of depression or depressed sate * Major depressive disorder, single episode (296.2) (excluding those accompanied by comorbid psychiatric disorders) * Major depressive disorder, recurrent (296.3) (excluding those accompanied by comorbid psychiatric disorders) * Age: \>= 20 years (at the time of obtaining consent) * Consent: Patients from whom written consent to participate in this study can be obtained * Gender: * Female patients of childbearing potential can be enrolled. But, such patients who can be enrolled are limited to only those who are negative in the pregnancy test performed at the start of the placebo run-in phase and who agree to receive a pregnancy test at the time point defined in the study period and surely perform any of the contraceptive methods. * Male subjects must abstain from (or use a condom during) sexual intercourse with a pregnant or lactating female. Male subjects must abstain from or use a condom plus spermicidal agent (foam/gel/film/cream/suppository) during sexual intercourse with a female of child-bearing potential. * Patients whose HAM-D (17 items) total score is \>= 20 points * Patients whose duration of current episode at least 12 weeks but no longer than 24 months * Patients whose score of depressed mood (HAM-D Item 1) is \>= 2 points * QTc\<450 millisecond (msec) or \<480 msec for patients with Bundle Branch Block - values based on either single ECG values or triplicate ECG averaged QTc values obtained over a brief recording period. For the purposes of these criteria, QTc B (Bazett's correction) is defined as (QT interval \[msec\]) /(square root of RR interval \[seconds\]) \<at the start of treatment phase\> Only the patients who meet all of the following conditions at Week -1 (at the start of the placebo run-in phase) and Week 0 (at the start of treatment phase) can be shifted to the treatment phase. * Patients whose HAM-D (17 items) total score is \>=20 points * Patients whose score of depressed mood (HAM-D Item 1) is \>=2 points
Exclusion criteria
\<at the start of placebo run-in phase\> The patients who are meeting any of the following conditions at Week -1 (at the start of placebo run-in phase) must not be enrolled in this study. * Patients whose primary diagnosis is a disorder classified to Axis I other than major depressive disorder in DSM-IV-TR classification (dysthymic disorder, eating disorder, specific phobia (monophobia), posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder, etc.) * Patients with a current DSM-IV-TR Axis II diagnosis that suggested non-responsiveness to pharmacotherapy or non- compliance with the protocol (e.g., antisocial or borderline personality disorder) * Patients with a history or complication of another (non-MDD) mental disorder (schizophrenia, etc.) * Patients with a history or complication of manic episodes * Patients diagnosed as having an attentional deficit disorder or hyperactivity disorder * Patients diagnosed as having a pervasive development disorder or mental retardation * Patients diagnosed as abusing or dependent on alcohol or drug within one year before the Week -1 visit * Patients who have undergone electroconvulsive therapy within one year before the Week -1 visit for the treatment of the current episode * Patients who have a history of treatment with depot neuroleptics * Patients with a history of serotonin syndrome or neuroleptic malignant syndrome * Patients with a \>= 3-point score of suicide (HAM-D Item 3) or patients whose Columbia Suicide Severity Rating Scale (C-SSRS) assessment suggests that they are or have been at significant risk for harming themselves or have actually harmed themselves, or who, in the opinion of the investigator (subinvestigator), are at significant risk for harming self or others. * Patients with a history of suicide attempt, self-injurious action (excluding action with no intention of suicide) or overdosage (excluding apparently accidental overdosage) * Patients who have taken another investigational product or a drug used in a post-marketing clinical study within 12 weeks before the Week -1 visit * Patients with glaucoma * Patients with a convulsive disorder such as epilepsy or a history of it * Patients using a drug increasing an onset risk of bleeding, patients with a bleeding tendency or bleeding diathesis * Patients complicated with severe renal or hepatic dysfunction * Patients complicated with serious organic brain disorder * Patients with a history or complication of cancer or malignant tumor * Patients complicated by chronic hepatitis B or C being positive in test of hepatitis B surface antigen (HbsAg) or hepatitis C antibody * Pregnant, lactating or possibly pregnant female patients, and female patients wishing to be pregnant during the study period * Patients who have previously been unresponsive to paroxetine therapy (e.g. \>4wks unresponsive to paroxetine for depression). * Patients with a history of having discontinued treatment due to an adverse event caused by paroxetine * Patients with a history of hypersensitivity to paroxetine. * Patients judged ineligible to participate in this study by the investigator or subinvestigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change From Baseline in the Hamilton Depression Rating Scale (HAM-D; 17 Items) Total Score at Week 8 | Baseline (Week 0) and Week 8 | The HAM-D measures the severity of depressive symptoms in participants with major depressive disorder (MDD). It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Mean change from baseline was calculated as the value at Week 8 minus the Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Baseline (Week 0); Weeks 1, 2, 3, 4, 6, and 8 | The HAM-D measures the severity of depressive symptoms in participants with MDD. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Mean change from baseline was calculated as the value at each time point minus the Baseline value. |
| Percentage of HAM-D Responders at Weeks 4 and 8 | Weeks 4 and 8 | The HAM-D measures the severity of depressive symptoms in participants with MDD. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is a sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Responders are defined as participants with a 50 percent or greater reduction from baseline in the HAM-D total score. |
| Percentage of HAM-D Remitters at Weeks 4 and 8 | Weeks 4 and 8 | The HAM-D measures the severity of depressive symptoms in participants with MDD. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Remitters are defined as participants with a HAM-D total score of 7 or less. |
| Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Baseline (Week 0); Weeks 1, 2, 3, 4, 6, and 8 | The 7-point CGI-SI scale assesses the clinician's impression of the participant's current illness state. Scores on the CGI-SI range from 1 = not ill at all to 7 = among the most extremely ill. Mean change from baseline was calculated as the value at each time point minus the baseline value. |
| Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 | Weeks 4 and 8 | The 7-point CGI-GI assesses the participant's improvement or worsening from baseline. Scores on the CGI-GI range from 1 = very much improved to 7 = very much worse. Responders are defined as participants with a score of 1 or 2 = much improved. |
Countries
Japan, South Korea
Participant flow
Pre-assignment details
Participants who had completed all the study procedures (up to the post-study examinations) were defined as per protocol completers.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matched to the controlled release formulation (CR) of paroxetine and placebo matched to the immediate release formulation (IR) of paroxetine were administered orally once daily from the start of the treatment phase (8 weeks) through the end of the taper phase (0-3 weeks). | 172 |
| Paroxetine CR An initial dose of 12.5 or 25 milligrams (mg)/day of paroxetine CR was administered orally once daily in the first week of the treatment phase. Thereafter, 25-50 mg/day was administered once daily for 7 weeks. In the second week, participants who started the treatment from 12.5 mg/day were forced to receive the uptitrated dose of 25 mg/day, and participants who started the treatment from 25 mg/day were maintained at the same dose level. The dose level was increased by 12.5 mg/day at intervals of at least 1 week until sufficient efficacy was confirmed. During the taper phase, the last dose level in the treatment phase was reduced by 12.5 mg/day at weekly intervals to the final dose level of 12.5 mg/day to complete the treatment. | 161 |
| Paroxetine IR An initial dose of 10 or 20 mg/day of paroxetine IR was administered orally once daily in the first week of the treatment phase. Thereafter, 20-40 mg/day was administered once daily for 7 weeks. In the second week, participants who started the treatment from 10 mg/day were forced to receive the uptitrated dose of 20 mg/day, and participants who started the treatment from 20 mg/day were maintained at the same dose level. The dose level was increased by 10 mg/day at intervals of at least 1 week until sufficient efficacy was confirmed. During the taper phase, the last dose level in the treatment phase was reduced by 10 mg/day at weekly intervals to the final dose level of 10 mg/day to complete the treatment. | 83 |
| Total | 416 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 12 | 13 | 9 |
| Overall Study | Lack of Efficacy | 7 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 | 0 |
| Overall Study | Met Protocol-defined Stopping Criteria | 5 | 1 | 1 |
| Overall Study | Physician Decision | 6 | 2 | 1 |
| Overall Study | Protocol Violation | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Paroxetine CR | Paroxetine IR | Total |
|---|---|---|---|---|
| Age, Continuous | 36.8 Years STANDARD_DEVIATION 10.04 | 36.4 Years STANDARD_DEVIATION 11.36 | 35.5 Years STANDARD_DEVIATION 10.38 | 36.4 Years STANDARD_DEVIATION 10.62 |
| Gender Female | 94 Participants | 86 Participants | 48 Participants | 228 Participants |
| Gender Male | 78 Participants | 75 Participants | 35 Participants | 188 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 17 participants | 20 participants | 10 participants | 47 participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 154 participants | 138 participants | 73 participants | 365 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 76 / 172 | 43 / 79 | 50 / 82 | 93 / 161 | 23 / 43 | 21 / 40 | 44 / 83 |
| serious Total, serious adverse events | 1 / 172 | 2 / 79 | 4 / 82 | 6 / 161 | 2 / 43 | 0 / 40 | 2 / 83 |
Outcome results
Primary
Adjusted Mean Change From Baseline in the Hamilton Depression Rating Scale (HAM-D; 17 Items) Total Score at Week 8
The HAM-D measures the severity of depressive symptoms in participants with major depressive disorder (MDD). It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Mean change from baseline was calculated as the value at Week 8 minus the Baseline value.
Time frame: Baseline (Week 0) and Week 8
Population: Full Analysis Set (FAS): all participants who entered the treatment phase (8 weeks), excluding those who had taken no dose of the investigational product for the treatment phase and who had no data on the HAM-D total score after the start of the treatment phase. The analysis was performed on the last observation carried forward (LOCF) dataset.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Adjusted Mean Change From Baseline in the Hamilton Depression Rating Scale (HAM-D; 17 Items) Total Score at Week 8 | -10.4 scores on a scale | Standard Error 0.62 |
| Paroxetine CR | Adjusted Mean Change From Baseline in the Hamilton Depression Rating Scale (HAM-D; 17 Items) Total Score at Week 8 | -12.8 scores on a scale | Standard Error 0.61 |
| Paroxetine IR | Adjusted Mean Change From Baseline in the Hamilton Depression Rating Scale (HAM-D; 17 Items) Total Score at Week 8 | -12.5 scores on a scale | Standard Error 0.78 |
p-value: <0.00195% CI: [-3.8, -1.1]ANCOVA
Secondary
Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8
The 7-point CGI-SI scale assesses the clinician's impression of the participant's current illness state. Scores on the CGI-SI range from 1 = not ill at all to 7 = among the most extremely ill. Mean change from baseline was calculated as the value at each time point minus the baseline value.
Time frame: Baseline (Week 0); Weeks 1, 2, 3, 4, 6, and 8
Population: FAS. The analysis was performed on the OC dataset. The analysis of Week 8 data was also performed on the LOCF dataset, where missing values were imputed by the last observed value in the longitudinal data. Some participants in each group were not included in the OC analysis because they had missing values or they were withdrawn prematurely.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 3, n=161, 155, 78 | -0.6 scores on a scale | Standard Deviation 0.83 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 1, n=171, 157, 83 | -0.1 scores on a scale | Standard Deviation 0.46 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 4, n=158, 153, 79 | -0.7 scores on a scale | Standard Deviation 0.85 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 8 LOCF, n=171, 158, 83 | -0.9 scores on a scale | Standard Deviation 1.02 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 8, n=144, 145, 74 | -1.0 scores on a scale | Standard Deviation 0.96 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 2, n=164, 155, 80 | -0.4 scores on a scale | Standard Deviation 0.68 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 6, n=151, 147, 76 | -0.9 scores on a scale | Standard Deviation 0.87 |
| Paroxetine CR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 2, n=164, 155, 80 | -0.4 scores on a scale | Standard Deviation 0.59 |
| Paroxetine CR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 1, n=171, 157, 83 | -0.2 scores on a scale | Standard Deviation 0.43 |
| Paroxetine CR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 3, n=161, 155, 78 | -0.7 scores on a scale | Standard Deviation 0.74 |
| Paroxetine CR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 4, n=158, 153, 79 | -0.8 scores on a scale | Standard Deviation 0.85 |
| Paroxetine CR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 6, n=151, 147, 76 | -1.1 scores on a scale | Standard Deviation 0.98 |
| Paroxetine CR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 8, n=144, 145, 74 | -1.3 scores on a scale | Standard Deviation 1.02 |
| Paroxetine CR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 8 LOCF, n=171, 158, 83 | -1.2 scores on a scale | Standard Deviation 1.02 |
| Paroxetine IR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 6, n=151, 147, 76 | -0.9 scores on a scale | Standard Deviation 0.9 |
| Paroxetine IR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 1, n=171, 157, 83 | -0.2 scores on a scale | Standard Deviation 0.58 |
| Paroxetine IR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 8 LOCF, n=171, 158, 83 | -1.1 scores on a scale | Standard Deviation 1.05 |
| Paroxetine IR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 3, n=161, 155, 78 | -0.6 scores on a scale | Standard Deviation 0.72 |
| Paroxetine IR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 8, n=144, 145, 74 | -1.3 scores on a scale | Standard Deviation 1.01 |
| Paroxetine IR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 4, n=158, 153, 79 | -0.8 scores on a scale | Standard Deviation 0.93 |
| Paroxetine IR | Mean Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-SI) Scores at Weeks 1, 2, 3, 4, 6, and 8 | Week 2, n=164, 155, 80 | -0.5 scores on a scale | Standard Deviation 0.67 |
Secondary
Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8
The HAM-D measures the severity of depressive symptoms in participants with MDD. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Mean change from baseline was calculated as the value at each time point minus the Baseline value.
Time frame: Baseline (Week 0); Weeks 1, 2, 3, 4, 6, and 8
Population: FAS. The analysis was performed on the following datasets: the observed case (OC) dataset for Week 1 and the LOCF dataset for Weeks 2, 3, 4, 6, and 8, where missing values were imputed by the last observed value in the longitudinal data. One participant in the Paroxetine CR group was not included in the OC analysis for having a missing value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 6, n=171, 158, 83 | -8.8 scores on a scale | Standard Deviation 6.4 |
| Placebo | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 4, n=171, 158, 83 | -8.0 scores on a scale | Standard Deviation 6.1 |
| Placebo | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 2, n=171, 158, 83 | -5.2 scores on a scale | Standard Deviation 5.11 |
| Placebo | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 1, n=171, 157, 83 | -3.1 scores on a scale | Standard Deviation 4.04 |
| Placebo | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 3, n=171, 158, 83 | -6.7 scores on a scale | Standard Deviation 6.05 |
| Placebo | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 8, n=171, 158, 83 | -9.8 scores on a scale | Standard Deviation 6.68 |
| Paroxetine CR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 3, n=171, 158, 83 | -7.5 scores on a scale | Standard Deviation 5.64 |
| Paroxetine CR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 4, n=171, 158, 83 | -9.3 scores on a scale | Standard Deviation 5.66 |
| Paroxetine CR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 6, n=171, 158, 83 | -10.9 scores on a scale | Standard Deviation 6.21 |
| Paroxetine CR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 1, n=171, 157, 83 | -2.9 scores on a scale | Standard Deviation 4.05 |
| Paroxetine CR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 8, n=171, 158, 83 | -12.4 scores on a scale | Standard Deviation 6.41 |
| Paroxetine CR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 2, n=171, 158, 83 | -5.5 scores on a scale | Standard Deviation 4.85 |
| Paroxetine IR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 6, n=171, 158, 83 | -10.4 scores on a scale | Standard Deviation 5.78 |
| Paroxetine IR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 4, n=171, 158, 83 | -9.1 scores on a scale | Standard Deviation 5.66 |
| Paroxetine IR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 8, n=171, 158, 83 | -12.0 scores on a scale | Standard Deviation 5.83 |
| Paroxetine IR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 1, n=171, 157, 83 | -3.5 scores on a scale | Standard Deviation 4.36 |
| Paroxetine IR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 3, n=171, 158, 83 | -7.3 scores on a scale | Standard Deviation 4.7 |
| Paroxetine IR | Mean Change From Baseline in the HAM-D Total Score at Weeks 1, 2, 3, 4, 6, and 8 | Week 2, n=171, 158, 83 | -6.2 scores on a scale | Standard Deviation 4.93 |
Secondary
Percentage of HAM-D Remitters at Weeks 4 and 8
The HAM-D measures the severity of depressive symptoms in participants with MDD. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Remitters are defined as participants with a HAM-D total score of 7 or less.
Time frame: Weeks 4 and 8
Population: FAS. The analysis was performed on the OC dataset. The analysis of Week 8 data was also performed on the LOCF dataset, where missing values were imputed by the last observed value in the longitudinal data. Some participants in each group were not included in the OC analysis because they were withdrawn prematurely.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of HAM-D Remitters at Weeks 4 and 8 | Week 8 (OC), n=144, 145, 74 | 26 percentage of remitters |
| Placebo | Percentage of HAM-D Remitters at Weeks 4 and 8 | Week 4, n=158, 154, 78 | 16 percentage of remitters |
| Placebo | Percentage of HAM-D Remitters at Weeks 4 and 8 | Week 8 LOCF, n=171, 158, 83 | 23 percentage of remitters |
| Paroxetine CR | Percentage of HAM-D Remitters at Weeks 4 and 8 | Week 8 (OC), n=144, 145, 74 | 38 percentage of remitters |
| Paroxetine CR | Percentage of HAM-D Remitters at Weeks 4 and 8 | Week 4, n=158, 154, 78 | 15 percentage of remitters |
| Paroxetine CR | Percentage of HAM-D Remitters at Weeks 4 and 8 | Week 8 LOCF, n=171, 158, 83 | 35 percentage of remitters |
| Paroxetine IR | Percentage of HAM-D Remitters at Weeks 4 and 8 | Week 4, n=158, 154, 78 | 18 percentage of remitters |
| Paroxetine IR | Percentage of HAM-D Remitters at Weeks 4 and 8 | Week 8 LOCF, n=171, 158, 83 | 36 percentage of remitters |
| Paroxetine IR | Percentage of HAM-D Remitters at Weeks 4 and 8 | Week 8 (OC), n=144, 145, 74 | 39 percentage of remitters |
Secondary
Percentage of HAM-D Responders at Weeks 4 and 8
The HAM-D measures the severity of depressive symptoms in participants with MDD. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is a sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. Responders are defined as participants with a 50 percent or greater reduction from baseline in the HAM-D total score.
Time frame: Weeks 4 and 8
Population: FAS. The analysis was performed on the OC dataset. The analysis of Week 8 data was also performed on the LOCF dataset, where missing values were imputed by the last observed value in the longitudinal data. Some participants in each group were not included in the OC analysis because they were withdrawn prematurely.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of HAM-D Responders at Weeks 4 and 8 | Week 8 (OC), n=144, 145, 74 | 52 percentage of responders |
| Placebo | Percentage of HAM-D Responders at Weeks 4 and 8 | Week 4, n=158, 154, 78 | 30 percentage of responders |
| Placebo | Percentage of HAM-D Responders at Weeks 4 and 8 | Week 8 LOCF, n=171, 158, 83 | 46 percentage of responders |
| Paroxetine CR | Percentage of HAM-D Responders at Weeks 4 and 8 | Week 8 (OC), n=144, 145, 74 | 66 percentage of responders |
| Paroxetine CR | Percentage of HAM-D Responders at Weeks 4 and 8 | Week 4, n=158, 154, 78 | 40 percentage of responders |
| Paroxetine CR | Percentage of HAM-D Responders at Weeks 4 and 8 | Week 8 LOCF, n=171, 158, 83 | 63 percentage of responders |
| Paroxetine IR | Percentage of HAM-D Responders at Weeks 4 and 8 | Week 4, n=158, 154, 78 | 40 percentage of responders |
| Paroxetine IR | Percentage of HAM-D Responders at Weeks 4 and 8 | Week 8 LOCF, n=171, 158, 83 | 57 percentage of responders |
| Paroxetine IR | Percentage of HAM-D Responders at Weeks 4 and 8 | Week 8 (OC), n=144, 145, 74 | 59 percentage of responders |
Secondary
Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8
The 7-point CGI-GI assesses the participant's improvement or worsening from baseline. Scores on the CGI-GI range from 1 = very much improved to 7 = very much worse. Responders are defined as participants with a score of 1 or 2 = much improved.
Time frame: Weeks 4 and 8
Population: FAS. The analysis was performed on the OC dataset. The analysis of Week 8 data was also performed on the LOCF dataset, where missing values were imputed by the last observed value in the longitudinal data. Some participants in each group were not included in the OC analysis because they had missing values or they were withdrawn prematurely.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 | Week 8 LOCF, n=171, 158, 83 | 53 percentage of responders |
| Placebo | Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 | Week 8 (OC), n=144, 145, 74 | 60 percentage of responders |
| Placebo | Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 | Week 4, n=158, 153, 79 | 40 percentage of responders |
| Paroxetine CR | Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 | Week 8 LOCF, n=171, 158, 83 | 71 percentage of responders |
| Paroxetine CR | Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 | Week 4, n=158, 153, 79 | 51 percentage of responders |
| Paroxetine CR | Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 | Week 8 (OC), n=144, 145, 74 | 76 percentage of responders |
| Paroxetine IR | Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 | Week 8 (OC), n=144, 145, 74 | 78 percentage of responders |
| Paroxetine IR | Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 | Week 4, n=158, 153, 79 | 56 percentage of responders |
| Paroxetine IR | Percentage of Responders Based on the Clinical Global Impression-Global Improvement (CGI-GI) Scores at Weeks 4 and 8 | Week 8 LOCF, n=171, 158, 83 | 75 percentage of responders |