Study to Evaluate the Efficacy, Safety and Tolerability of Bupropion Hydrochloride Extended-release Tablet, and Escitalopram Oxalate Capsule in Subjects With Major Depressive Disorder

A Multi-centre, Randomised, Double-blind, Parallel Active-controlled Study Evaluating the Efficacy, Safety and Tolerability of Bupropion Hydrochloride Extended-release (Bupropion XL 300mg Once Daily), Escitalopram Oxalate (Escitalopram, 10mg-20mg Once Daily) in Subjects With Major Depressive Disorder

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02191397

Enrollment

534

Registered

2014-07-16

Start date

2015-02-10

Completion date

2016-10-25

Last updated

2020-02-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Depressive Disorder, Major

Keywords

Escitalopram, Major depressive disorder, Non-inferiority, Bupropion

Brief summary

This multi-centre study will follow a randomised, double-blind, parallel-group, active-controlled design and will evaluate the efficacy, safety and tolerability of bupropion extended-release (XL) (300 mg/day) compared with escitalopram (10-20 mg/day) in outpatients and inpatients with major depressive disorder (MDD). The total duration of the study will be 11 weeks consisting of three phases. The screening phase (phase I) will be lasting for 0-14 days, subjects will be randomised to bupropion XL or escitalopram in a 1:1 ratio for acute phase treatment phase (phase II) for 8 weeks. There are 3 dose levels during this acute treatment phase. The 3-dose level plan is designed to ensure each drug is titrated according to the prescribing information and to reach an optimal clinical dose. Finally patients will enter the taper phase (phase III) for up to 1 week to assess and reduce the possible withdrawal symptoms. In China almost all existing antidepressants are available on the market, but bupropion XL has not yet been approved. This Phase III clinical trial will be used for the purpose of registering bupropion XL in China.

Interventions

DRUGBupropion

Bupropion is an extended-release plain creamy white colored tablet which contains bupropion hydrochloride equivalent to 150 mg of bupropion.

DRUGBupropion Matching Placebo

Bupropion hydrochloride matching placebo tablets will be supplied to maintain blinding

DRUGEscitalopram

Escitalopram is available as a Swedish orange capsule containing escitalopram oxalate equivalent to 10 mg of escitalopram.

DRUGEscitalopram Matching Placebo

Escitalopram oxalate matching placebo tablets will be supplied to maintain blinding

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Subjects must have the ability to effectively communicate with investigator, complete study related documents, comprehend the key components of the consent form and must provide written informed consent to participate in the study prior to any study-specific assessments or procedures. * An in- patient or out-patient (male or female) and aged \>=18 years. * A diagnosis of MDD, nonpsychotic, single episode or recurrent, Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) (296.2/296.3), utilizing the Mini International Neuropsychiatric Interview (MINI). * Established MDD diagnosis with a duration of at least 4 weeks. * HAMD-17 total score of \>=20 and a CGI-S score of \>=4 at both the Screening Visit and the Baseline Visit. * Subject must be in general good health and be considered clinically appropriate for therapy with bupropion or escitalopram, based upon the investigator's overall clinical evaluation. * Female patients of child-bearing potential only: patients must not be lactating and must test negative for pregnancy at screening and agree to use a medically accepted method of birth control during the study. * Liver function tests: alanine aminotransferase (ALT) \<2x upper limit of normal (ULN); alkaline phosphatase and bilirubin \<=1.5xULN (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Corrected QT (QTc) criteria： QTc \<450 milliseconds (msec) or QTc \<480msec for patients with bundle branch block. The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purpose of data analysis, QTcF will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.

Exclusion criteria

* Has been diagnosed or received treatment for a primary Axis I disorder with the exception of MDD (including current or past diagnosis of anorexia nervosa or bulimia). Additionally, subjects diagnosed with dysthymic disorder within the past 2 years will be excluded. * Current DSM-IV Axis II diagnosis that suggests non-compliance with the protocol. * A subject who, in the assessment with the Columbia Suicide Severity Rating Scale (C-SSRS) and investigator's judgment, poses suicidal risk, or had suicide attempt or behavior within 6 months prior to the Screening Visit. * Current or past history of seizure disorder or brain injury (traumatic or disease related); or any condition which, in the opinion of the investigator, predisposed to seizure; subjects treated with other medications or treatment regimes that lower seizure threshold. Note: single childhood febrile seizure is not exclusionary. * In the Investigator's judgment, presence of clinically significant laboratory test results (including ECG, hematology, chemistry and urine), or the conditions which render patients unsuitable for the study (such as serious cardiovascular disease, uncontrolled hypertension, liver or renal insufficiency) and pose a safety concern or interfere with the accurate safety and efficacy assessments. Subjects with co-morbidities (such as diabetes, hypertension, hypothyroid, chronic respiratory diseases or other physical illness) were eligible if their condition had been stable for at least three months and they had been receiving standard therapy for the condition for at least three months. * Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) * Frequent and/or severe allergic reactions with multiple medications, or history of a medically significant adverse effect (including allergic reaction) from any medications or compounds in the study. * Use of prohibited psychotropic drugs not allowed within seven days (14 days for monoamine oxidase inhibitors (MAOIs), 30 days for fluoxetine) prior to the Baseline Visit. * Subjects who have attended any studies investigating bupropion or escitalopram 6 months prior to this study, or use of bupropion or escitalopram in the last 4 weeks. * Participation in other clinical studies unrelated to the current illness within 30 days or participation in other clinical studies related to the current illness within 3 months. * Initiation of systematic psychotherapy within three months prior to the Screening Visit, or plans to initiate systematic psychotherapy during the study. * Received electroconvulsive therapy (ECT), modify electroconvulsive therapy (MECT), transcranial magnetic stimulation (TMS), or other physical therapy within the 6 months prior to the Screening Visit. * Previous failure of bupropion or escitalopram treatment with adequate courses and doses. * Previous or present failure of two different classes of antidepressants treatment with adequate courses (e.g. maximum labelled doses for \>=4 weeks). * History of substance abuse (alcohol or drugs) or substance dependence within 12 months (as defined in the DSM-IV). * Other conditions which, in the Investigator's judgment, render patients unsuitable for the clinical study.

Design outcomes

Primary

Measure	Time frame	Description
Mean Change in Hamilton Depression Rating Scale - 17 (HAMD-17) Total Score From Baseline to End of Acute Treatment Phase (Week 8)	Baseline (Week 0) and Week 8	HAMD-17 is used to assess the severity of depression and symptom improvement. It consisted of 17 questions. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Change from Baseline was calculated by subtracting the Baseline total score (at Day 0, Week 0) from Week 8 observed total score. The Per Protocol (PP) Population is defined as all randomized participants in the Intent-To-Treat (ITT) Population who do not meet criteria of a major protocol deviation, with overall compliance of active drug for acute treatment phase in the range of 75%-125% and complete the first 6 weeks treatment and has HAMD-17 assessment at/after week 6 (that is \>=35 days). All participants in the PP population were included in the mixed model repeated measures analysis. Only those participants with data available at the specified time point were analyzed.

Secondary

Measure	Time frame	Description
Remission Rate Based on HAMD-17 Total Score	Up to Week 8	HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Remission was defined as HAMD-17 total scores at end of acute treatment phase (Week 8) \<=7.
Sustained Response Rate Based on HAMD-17 Total Score	Up to Week 8	HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Sustained response was defined as response at end of acute treatment phase and an earlier visit and the decrease from Baseline in non-missing HAMD-17 total scores at all visits between these two visits by at least 40%.
Sustained Remission Rate Based on HAMD-17 Total Score	Up to Week 8	HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Sustained remission was defined as remission at end of acute treatment phase and an earlier visit and non-missing HAMD-17 total scores at all visits between these two visits \<=8.
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8	MADRS is a 10-point rating scale. Each item is scored on a scale of 0-6, with a total score range of 0-60. Higher score indicates worst symptoms. This scale is mainly used to assess the efficacy of antidepressant treatment. The ratings were based on the signs and symptoms during the preceding week prior to the visit. Values at Day0, Week 0 was considered as Baseline value. The observed MADRS total score was considered as missing if any item is missing. Change from Baseline in MADRS was obtained by subtracting the Baseline value from the specific post-Baseline value. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8	For CGI-I rating, the raters indicated their assessment of the participant's total improvement or worsening compared to the participant's condition at the Baseline visit, whether or not the improvement or worsening was thought to be treatment related. Scores ranges from 0 to 7 where 0 represents Not assessed, and the remaining values 1-7 represent Very much improved (1) to Very much worse (7). Participants with score 0 were excluded from analysis. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8	HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Depressed Mood Subscale is a factor score of item-1 (Depressed Mood) of HAMD-17 scale. This subscale has a score in a range of 0 (absence of depressed mood feelings) to 4 (when participants report virtually only these feeling states in his/her spontaneous verbal and non-verbal communicationtotal score). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8	HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Anxiety/Somatization subscale score was derived as sum of scores of items 10, 11, 12, 13, 15 and 17 from HAMD-17. This subscale has a score in a range of 0 (absence of condition) to 18 (most severe condition). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8	HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Retardation subscale score was derived as sum of scores of items 1, 7, 8 and 14 from HAMD-17. This subscale has a score in a range of 0 (absence of condition) to 14 (most severe condition). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8	HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Sleep Disorder subscale score was derived as sum of scores of items 4, 5 and 6 from HAMD-17. This subscale has a score in a range of 0 (absence of condition) to 6 (most severe condition). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8	CGI-S records the severity of illness at specific time points, with a range of responses from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Participants with zero values (0) representing Not assessed were excluded from analysis. Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was obtained by subtracting the Baseline value from the specific post-Baseline value. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious AE (SAE)	Up to Week 10	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants who received any of the study treatment and had any non-serious AE or SAE were considered for analysis. Safety Population comprised of all participants who took at least one dose of the study medication.
Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Up to Week 10	Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Response Rate Based on HAMD-17 Total Score	Up to Week 8	HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Response was defined as decrease in HAMD-17 total scores at end of acute treatment phase (Week 8) relative to Baseline by at least 50%. Non-responder Imputation was used in calculation of rates.
Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Up to Week 10	Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Up to Week 10	Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	Up to Week 10	Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Up to Week 10	Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points	Up to Week 10	Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points	Up to Week 10	Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points	Up to Week 10	Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Number of Participants With Urinalysis Data Outside the Normal Range	Up to Week 10	Urine samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Number of participants with urine specific gravity and potential of hydrogen (pH) outside (higher or lower) the normal range are presented. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	Up to Week 10	Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were taken at Screening (within 14 days prior to dosing), randomization visit (Week 0) and at Weeks 1, 2, 4, 6, 8, Taper visit (Week 9) and Follow-up visit (Week 10). SBP \<30 or \>170 millimeter of mercury (mmHg); DBP \<20 or \>110 mmHg and heart rate \<40 or \>120 beats per minute (bpm) were considered as values outside of clinical concern range and were presented as 'High' or 'Low' values. Number of participants with vital signs outside of clinical concern range at any post-Baseline visit are presented. Only those participants with data available at the specified time points were analyzed.
Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	Up to Week 10	ECG was recorded at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). PR interval \<110 or \>220 millisecond (msec); QRS interval \<60 or \>120 msec and corrected QT (QTc) interval \>450 msec were considered as values outside of clinical concern range and were presented as 'High' or 'Low' values. Number of participants with ECG data outside of clinical concern range at any post-Baseline visit are presented. Only those participants with data available at the specified time points were analyzed.
Change From Baseline in Changes in Sexual Function Questionnaire (CSFQ)	Baseline (Day 0) and Week 8	CSFQ is a questionnaire about sexual activity and sexual function (sexual intercourse, masturbation, sexual fantasies and other activity). CSFQ is a gender-specific questionnaire. Both male and female versions consist of 14 items, each with 5 possible answers. CSFQ has a score in a range of 14 to 70. Higher score indicates higher sexual activity and sexual function. Value at Day 0 (Week 0) was considered as Baseline value. Change from Baseline at Week 8 was calculated by subtracting the Baseline score from the specific post-Baseline score. Only those participants with data available at the specified time points were analyzed.
Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)	Baseline and up to Taper visit (Week 9)	C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. It consists of 10 items, each with two possible answers (yes/no). Suicidal ideation was interpreted if yes answer at any time during treatment to any one of the five suicidal ideation questions (item 1-5) on the C-SSRS. Suicidal behavior was interpreted if a yes answer at any time during treatment to any one of the five suicidal behavior questions (item 6-10) on the C-SSRS. Suicidal ideation or behavior is interpreted if a yes answer at any time during treatment to any one of the ten suicidal ideation and behavior questions (item 1-10) on the C-SSRS. Number of participants with at least one on-treatment C-SSRS assessment were analyzed. Only those participants with data available at the specified time points were analyzed.
Change From Baseline in Hematocrit at the Indicated Time Points	Up to Week 10	Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Countries

China

Participant flow

Recruitment details

This was a multi-center, randomized, double-blind, parallel active-controlled study to evaluate the efficacy, safety and tolerability of bupropion hydrochloride extended-release (XL) and escitalopram oxalate in participants with major depressive disorder. This study was conducted in China from 10-February-2015 to 25-October-2016.

Pre-assignment details

The study had screening phase (up to 14 days), 8-week double blind treatment phase and taper phase (up to 1 week). A total of 655 participants were screened and 538 were randomized into the study. 4 participants were randomized but discontinued prior to receiving any study treatment. Hence, the Safety Population was comprised of 534 participants.

Participants by arm

Arm	Count
Bupropion XL In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.	266
Escitalopram In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.	268
Total	534

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	28	17
Overall Study	Lack of Efficacy	10	5
Overall Study	Lost to Follow-up	10	11
Overall Study	Met protocol-defined stopping criteria	5	4
Overall Study	Physician Decision	8	3
Overall Study	Protocol Violation	0	3
Overall Study	Withdrawal by Subject	22	27

Baseline characteristics

Characteristic	Bupropion XL	Escitalopram	Total
Age, Continuous	36.9 Years STANDARD_DEVIATION 11.92	37.6 Years STANDARD_DEVIATION 12.09	37.3 Years STANDARD_DEVIATION 12
Race/Ethnicity, Customized Asian - East Asian Heritage	266 Participants	268 Participants	534 Participants
Sex: Female, Male Female	168 Participants	172 Participants	340 Participants
Sex: Female, Male Male	98 Participants	96 Participants	194 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 266	0 / 268
other Total, other adverse events	151 / 266	150 / 268
serious Total, serious adverse events	10 / 266	11 / 268

Outcome results

Primary

Mean Change in Hamilton Depression Rating Scale - 17 (HAMD-17) Total Score From Baseline to End of Acute Treatment Phase (Week 8)

HAMD-17 is used to assess the severity of depression and symptom improvement. It consisted of 17 questions. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Change from Baseline was calculated by subtracting the Baseline total score (at Day 0, Week 0) from Week 8 observed total score. The Per Protocol (PP) Population is defined as all randomized participants in the Intent-To-Treat (ITT) Population who do not meet criteria of a major protocol deviation, with overall compliance of active drug for acute treatment phase in the range of 75%-125% and complete the first 6 weeks treatment and has HAMD-17 assessment at/after week 6 (that is \>=35 days). All participants in the PP population were included in the mixed model repeated measures analysis. Only those participants with data available at the specified time point were analyzed.

Time frame: Baseline (Week 0) and Week 8

Population: PP Population

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Bupropion XL	Mean Change in Hamilton Depression Rating Scale - 17 (HAMD-17) Total Score From Baseline to End of Acute Treatment Phase (Week 8)	-14.5 Scores on a scale	Standard Error 0.41
Escitalopram	Mean Change in Hamilton Depression Rating Scale - 17 (HAMD-17) Total Score From Baseline to End of Acute Treatment Phase (Week 8)	-15.4 Scores on a scale	Standard Error 0.39

p-value: 0.13995% CI: [-0.27, 1.94]Mixed model repeated measures analysis

Secondary

Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points

Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALP, Taper, n=12, 15	3.674 International Units per liter (IU/L)	Standard Deviation 11.5803
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	AST, Follow-up, n=8, 12	0.925 International Units per liter (IU/L)	Standard Deviation 23.3485
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALT, Taper, n=12, 16	7.993 International Units per liter (IU/L)	Standard Deviation 17.5985
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	GGT, Week 8, n=175, 181	0.688 International Units per liter (IU/L)	Standard Deviation 17.0699
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALP, Follow-up, n=7, 12	5.643 International Units per liter (IU/L)	Standard Deviation 9.2858
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	GGT, Taper, n=12, 15	1.403 International Units per liter (IU/L)	Standard Deviation 6.2977
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALP, Week 8, n=176, 181	1.866 International Units per liter (IU/L)	Standard Deviation 13.2776
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	GGT, Follow-up, n=7, 12	-2.029 International Units per liter (IU/L)	Standard Deviation 5.9637
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	AST, Week 8, n=176, 183	0.330 International Units per liter (IU/L)	Standard Deviation 7.6259
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	LD, Week 8, n=176, 182	1.292 International Units per liter (IU/L)	Standard Deviation 32.4627
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALT, Follow-up, n=8, 12	-7.337 International Units per liter (IU/L)	Standard Deviation 21.7809
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	LD, Taper, n=13, 13	14.463 International Units per liter (IU/L)	Standard Deviation 28.9571
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	AST, Taper, n=12, 16	3.193 International Units per liter (IU/L)	Standard Deviation 7.499
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	LD, Follow-up, n=8, 10	11.037 International Units per liter (IU/L)	Standard Deviation 45.3316
Bupropion XL	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALT, Week 8, n=176, 183	2.254 International Units per liter (IU/L)	Standard Deviation 14.7208
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	LD, Follow-up, n=8, 10	-4.150 International Units per liter (IU/L)	Standard Deviation 33.8871
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALT, Week 8, n=176, 183	1.315 International Units per liter (IU/L)	Standard Deviation 10.3019
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALT, Taper, n=12, 16	-1.812 International Units per liter (IU/L)	Standard Deviation 15.1544
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALT, Follow-up, n=8, 12	5.938 International Units per liter (IU/L)	Standard Deviation 19.8234
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALP, Week 8, n=176, 181	0.407 International Units per liter (IU/L)	Standard Deviation 11.787
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALP, Taper, n=12, 15	3.480 International Units per liter (IU/L)	Standard Deviation 19.2823
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	ALP, Follow-up, n=7, 12	-3.953 International Units per liter (IU/L)	Standard Deviation 11.6377
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	AST, Week 8, n=176, 183	1.099 International Units per liter (IU/L)	Standard Deviation 6.1029
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	AST, Taper, n=12, 16	0.381 International Units per liter (IU/L)	Standard Deviation 6.0938
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	AST, Follow-up, n=8, 12	2.867 International Units per liter (IU/L)	Standard Deviation 11.0264
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	GGT, Week 8, n=175, 181	-0.694 International Units per liter (IU/L)	Standard Deviation 11.1878
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	GGT, Taper, n=12, 15	-3.133 International Units per liter (IU/L)	Standard Deviation 4.8019
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	GGT, Follow-up, n=7, 12	3.916 International Units per liter (IU/L)	Standard Deviation 25.9888
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	LD, Week 8, n=176, 182	2.879 International Units per liter (IU/L)	Standard Deviation 27.3838
Escitalopram	Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points	LD, Taper, n=13, 13	-8.092 International Units per liter (IU/L)	Standard Deviation 55.0095

Secondary

Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Cholesterol, Week 8, n=175, 181	-0.122 Millimole per liter (mmol/L)	Standard Deviation 0.5855
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Calcium, Taper, n=12, 12	-0.019 Millimole per liter (mmol/L)	Standard Deviation 0.1906
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Calcium, Follow-up, n=8, 11	-0.060 Millimole per liter (mmol/L)	Standard Deviation 0.1032
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Chloride, Week 8, n=173, 182	0.259 Millimole per liter (mmol/L)	Standard Deviation 2.7943
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Chloride, Taper, n=10, 13	-0.498 Millimole per liter (mmol/L)	Standard Deviation 3.2001
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Chloride, Follow-up, n=8, 8	-0.287 Millimole per liter (mmol/L)	Standard Deviation 3.6588
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Calcium, Week 8, n=173, 183	-0.017 Millimole per liter (mmol/L)	Standard Deviation 0.1139
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Cholesterol, Taper, n=12, 14	0.022 Millimole per liter (mmol/L)	Standard Deviation 0.5891
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Cholesterol, Follow-up, n=9, 11	-0.124 Millimole per liter (mmol/L)	Standard Deviation 0.5149
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Glucose, Week 8, n=173, 181	-0.051 Millimole per liter (mmol/L)	Standard Deviation 0.6327
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Glucose, Taper, n=12, 16	0.352 Millimole per liter (mmol/L)	Standard Deviation 0.3822
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Glucose, Follow-up, n=9, 11	-0.194 Millimole per liter (mmol/L)	Standard Deviation 0.4089
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Potassium, Week 8, n=173, 182	-0.021 Millimole per liter (mmol/L)	Standard Deviation 0.3504
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Potassium, Taper, n=10, 13	-0.114 Millimole per liter (mmol/L)	Standard Deviation 0.4165
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Potassium, Follow-up, n=8, 8	-0.110 Millimole per liter (mmol/L)	Standard Deviation 0.6221
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Sodium, Week 8, n=173, 182	-0.205 Millimole per liter (mmol/L)	Standard Deviation 2.4757
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Sodium, Taper, n=10, 13	-0.611 Millimole per liter (mmol/L)	Standard Deviation 3.0799
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Sodium, Follow-up, n=8, 8	-0.175 Millimole per liter (mmol/L)	Standard Deviation 3.9085
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Triglycerides, Week 8, n=175, 181	0.003 Millimole per liter (mmol/L)	Standard Deviation 1.0499
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Triglycerides, Taper, n=13, 15	-0.032 Millimole per liter (mmol/L)	Standard Deviation 0.4359
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Triglycerides, Follow-up, n=9, 11	0.637 Millimole per liter (mmol/L)	Standard Deviation 1.4045
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Urea, Week 8, n=174, 183	-0.068 Millimole per liter (mmol/L)	Standard Deviation 1.3282
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Urea, Taper, n=12, 16	0.517 Millimole per liter (mmol/L)	Standard Deviation 0.9249
Bupropion XL	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Urea, Follow-up, n=8, 11	0.687 Millimole per liter (mmol/L)	Standard Deviation 0.6998
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Urea, Taper, n=12, 16	-0.269 Millimole per liter (mmol/L)	Standard Deviation 1.0223
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Calcium, Week 8, n=173, 183	-0.020 Millimole per liter (mmol/L)	Standard Deviation 0.1225
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Potassium, Week 8, n=173, 182	0.009 Millimole per liter (mmol/L)	Standard Deviation 0.3552
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Calcium, Taper, n=12, 12	0.012 Millimole per liter (mmol/L)	Standard Deviation 0.1091
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Triglycerides, Week 8, n=175, 181	0.022 Millimole per liter (mmol/L)	Standard Deviation 0.5844
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Calcium, Follow-up, n=8, 11	-0.060 Millimole per liter (mmol/L)	Standard Deviation 0.1352
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Potassium, Taper, n=10, 13	0.046 Millimole per liter (mmol/L)	Standard Deviation 0.5095
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Chloride, Week 8, n=173, 182	-0.293 Millimole per liter (mmol/L)	Standard Deviation 2.5913
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Urea, Week 8, n=174, 183	0.015 Millimole per liter (mmol/L)	Standard Deviation 1.1723
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Chloride, Taper, n=10, 13	-0.566 Millimole per liter (mmol/L)	Standard Deviation 2.4684
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Potassium, Follow-up, n=8, 8	0.036 Millimole per liter (mmol/L)	Standard Deviation 0.6556
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Chloride, Follow-up, n=8, 8	-0.178 Millimole per liter (mmol/L)	Standard Deviation 4.6453
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Triglycerides, Taper, n=13, 15	0.574 Millimole per liter (mmol/L)	Standard Deviation 2.0355
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Cholesterol, Week 8, n=175, 181	0.051 Millimole per liter (mmol/L)	Standard Deviation 0.5931
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Sodium, Week 8, n=173, 182	-0.178 Millimole per liter (mmol/L)	Standard Deviation 2.5481
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Cholesterol, Taper, n=12, 14	0.082 Millimole per liter (mmol/L)	Standard Deviation 0.5991
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Urea, Follow-up, n=8, 11	-0.419 Millimole per liter (mmol/L)	Standard Deviation 1.0801
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Cholesterol, Follow-up, n=9, 11	-0.122 Millimole per liter (mmol/L)	Standard Deviation 0.5899
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Sodium, Taper, n=10, 13	0.978 Millimole per liter (mmol/L)	Standard Deviation 1.5853
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Glucose, Week 8, n=173, 181	-0.050 Millimole per liter (mmol/L)	Standard Deviation 0.5871
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Triglycerides, Follow-up, n=9, 11	0.181 Millimole per liter (mmol/L)	Standard Deviation 0.7767
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Glucose, Taper, n=12, 16	0.106 Millimole per liter (mmol/L)	Standard Deviation 0.9661
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Sodium, Follow-up, n=8, 8	0.770 Millimole per liter (mmol/L)	Standard Deviation 3.6011
Escitalopram	Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points	Glucose, Follow-up, n=9, 11	0.025 Millimole per liter (mmol/L)	Standard Deviation 1.2117

Secondary

Change From Baseline in Changes in Sexual Function Questionnaire (CSFQ)

CSFQ is a questionnaire about sexual activity and sexual function (sexual intercourse, masturbation, sexual fantasies and other activity). CSFQ is a gender-specific questionnaire. Both male and female versions consist of 14 items, each with 5 possible answers. CSFQ has a score in a range of 14 to 70. Higher score indicates higher sexual activity and sexual function. Value at Day 0 (Week 0) was considered as Baseline value. Change from Baseline at Week 8 was calculated by subtracting the Baseline score from the specific post-Baseline score. Only those participants with data available at the specified time points were analyzed.

Time frame: Baseline (Day 0) and Week 8

Population: Safety Population

Arm	Measure	Value (MEAN)	Dispersion
Bupropion XL	Change From Baseline in Changes in Sexual Function Questionnaire (CSFQ)	3.0 Scores on a scale	Standard Deviation 6.47
Escitalopram	Change From Baseline in Changes in Sexual Function Questionnaire (CSFQ)	0.9 Scores on a scale	Standard Deviation 7.21

Secondary

Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8

CGI-S records the severity of illness at specific time points, with a range of responses from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Participants with zero values (0) representing Not assessed were excluded from analysis. Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was obtained by subtracting the Baseline value from the specific post-Baseline value. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.

Time frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8

Population: PP Population

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Bupropion XL	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-0.7 Scores on a scale	Standard Error 0.05
Bupropion XL	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	-1.6 Scores on a scale	Standard Error 0.07
Bupropion XL	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-1.1 Scores on a scale	Standard Error 0.07
Bupropion XL	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-2.1 Scores on a scale	Standard Error 0.07
Bupropion XL	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-0.3 Scores on a scale	Standard Error 0.04
Escitalopram	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-2.2 Scores on a scale	Standard Error 0.07
Escitalopram	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-0.4 Scores on a scale	Standard Error 0.04
Escitalopram	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-0.8 Scores on a scale	Standard Error 0.05
Escitalopram	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-1.3 Scores on a scale	Standard Error 0.06
Escitalopram	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	-1.7 Scores on a scale	Standard Error 0.07

p-value: 0.80495% CI: [-0.1, 0.13]Mixed model repeated measures analysis

p-value: 0.07995% CI: [-0.02, 0.28]Mixed model repeated measures analysis

p-value: 0.03695% CI: [0.01, 0.38]Mixed model repeated measures analysis

p-value: 0.24895% CI: [-0.08, 0.31]Mixed model repeated measures analysis

p-value: 0.1195% CI: [-0.04, 0.35]Mixed model repeated measures analysis

Secondary

Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8

HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Anxiety/Somatization subscale score was derived as sum of scores of items 10, 11, 12, 13, 15 and 17 from HAMD-17. This subscale has a score in a range of 0 (absence of condition) to 18 (most severe condition). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.

Time frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8

Population: PP Population

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Bupropion XL	Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-2.0 Scores on a scale	Standard Error 0.15
Bupropion XL	Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	-4.0 Scores on a scale	Standard Error 0.17
Bupropion XL	Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-3.0 Scores on a scale	Standard Error 0.19
Bupropion XL	Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-4.8 Scores on a scale	Standard Error 0.16
Bupropion XL	Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-1.3 Scores on a scale	Standard Error 0.12
Escitalopram	Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-5.1 Scores on a scale	Standard Error 0.16
Escitalopram	Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-1.1 Scores on a scale	Standard Error 0.12
Escitalopram	Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-2.4 Scores on a scale	Standard Error 0.14
Escitalopram	Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-3.4 Scores on a scale	Standard Error 0.18
Escitalopram	Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	-4.4 Scores on a scale	Standard Error 0.17

p-value: 0.35895% CI: [-0.5, 0.18]Mixed model repeated measures analysis

p-value: 0.08195% CI: [-0.04, 0.75]Mixed model repeated measures analysis

p-value: 0.06295% CI: [-0.02, 0.99]Mixed model repeated measures analysis

p-value: 0.11895% CI: [-0.1, 0.85]Mixed model repeated measures analysis

p-value: 0.25295% CI: [-0.19, 0.71]Mixed model repeated measures analysis

Secondary

Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8

HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Depressed Mood Subscale is a factor score of item-1 (Depressed Mood) of HAMD-17 scale. This subscale has a score in a range of 0 (absence of depressed mood feelings) to 4 (when participants report virtually only these feeling states in his/her spontaneous verbal and non-verbal communicationtotal score). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.

Time frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8

Population: PP Population

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Bupropion XL	Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-1.1 Scores on a scale	Standard Deviation 0.06
Bupropion XL	Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	-1.5 Scores on a scale	Standard Deviation 0.06
Bupropion XL	Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-1.9 Scores on a scale	Standard Deviation 0.06
Bupropion XL	Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-0.4 Scores on a scale	Standard Deviation 0.04
Bupropion XL	Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-0.7 Scores on a scale	Standard Deviation 0.06
Escitalopram	Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-0.8 Scores on a scale	Standard Deviation 0.05
Escitalopram	Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-0.4 Scores on a scale	Standard Deviation 0.04
Escitalopram	Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	-1.6 Scores on a scale	Standard Deviation 0.06
Escitalopram	Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-1.3 Scores on a scale	Standard Deviation 0.06
Escitalopram	Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-1.9 Scores on a scale	Standard Deviation 0.06

p-value: 0.57995% CI: [-0.09, 0.16]Mixed model repeated measures analysis

p-value: 0.16395% CI: [-0.04, 0.26]Mixed model repeated measures analysis

p-value: 0.0595% CI: [0, 0.34]Mixed model repeated measures analysis

p-value: 0.33795% CI: [-0.09, 0.26]Mixed model repeated measures analysis

p-value: 0.71495% CI: [-0.14, 0.2]Mixed model repeated measures analysis

Secondary

Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8

HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Retardation subscale score was derived as sum of scores of items 1, 7, 8 and 14 from HAMD-17. This subscale has a score in a range of 0 (absence of condition) to 14 (most severe condition). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.

Time frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8

Population: PP Population

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Bupropion XL	Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-1.8 Scores on a scale	Standard Error 0.13
Bupropion XL	Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	-3.9 Scores on a scale	Standard Error 0.16
Bupropion XL	Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-2.9 Scores on a scale	Standard Error 0.15
Bupropion XL	Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-4.7 Scores on a scale	Standard Error 0.17
Bupropion XL	Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-1.0 Scores on a scale	Standard Error 0.1
Escitalopram	Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-4.9 Scores on a scale	Standard Error 0.16
Escitalopram	Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-1.0 Scores on a scale	Standard Error 0.1
Escitalopram	Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-2.0 Scores on a scale	Standard Error 0.13
Escitalopram	Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-3.1 Scores on a scale	Standard Error 0.15
Escitalopram	Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	-3.9 Scores on a scale	Standard Error 0.16

p-value: 0.57395% CI: [-0.2, 0.35]Mixed model repeated measures analysis

p-value: 0.20995% CI: [-0.13, 0.58]Mixed model repeated measures analysis

p-value: 0.42795% CI: [-0.25, 0.58]Mixed model repeated measures analysis

p-value: 0.85195% CI: [-0.4, 0.48]Mixed model repeated measures analysis

p-value: 0.3795% CI: [-0.25, 0.66]Mixed model repeated measures analysis

Secondary

Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8

HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Sleep Disorder subscale score was derived as sum of scores of items 4, 5 and 6 from HAMD-17. This subscale has a score in a range of 0 (absence of condition) to 6 (most severe condition). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.

Time frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8

Population: PP Population

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Bupropion XL	Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-0.8 Scores on a scale	Standard Error 0.11
Bupropion XL	Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	-1.8 Scores on a scale	Standard Error 0.11
Bupropion XL	Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-1.4 Scores on a scale	Standard Error 0.11
Bupropion XL	Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-2.3 Scores on a scale	Standard Error 0.11
Bupropion XL	Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-0.6 Scores on a scale	Standard Error 0.1
Escitalopram	Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-2.4 Scores on a scale	Standard Error 0.11
Escitalopram	Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-0.7 Scores on a scale	Standard Error 0.09
Escitalopram	Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-1.2 Scores on a scale	Standard Error 0.1
Escitalopram	Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-1.6 Scores on a scale	Standard Error 0.11
Escitalopram	Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	-2.0 Scores on a scale	Standard Error 0.11

p-value: 0.43895% CI: [-0.16, 0.37]Mixed model repeated measures analysis

p-value: 0.01495% CI: [0.07, 0.66]Mixed model repeated measures analysis

p-value: 0.20795% CI: [-0.11, 0.5]Mixed model repeated measures analysis

p-value: 0.13795% CI: [-0.07, 0.54]Mixed model repeated measures analysis

p-value: 0.29995% CI: [-0.14, 0.46]Mixed model repeated measures analysis

Secondary

Change From Baseline in Hematocrit at the Indicated Time Points

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Bupropion XL	Change From Baseline in Hematocrit at the Indicated Time Points	Hematocrit, Week 8, n=176, 183	0.0016 Proportion of red blood cells in blood	Standard Deviation 0.06088
Bupropion XL	Change From Baseline in Hematocrit at the Indicated Time Points	Hematocrit, Taper, n=13, 16	-0.0051 Proportion of red blood cells in blood	Standard Deviation 0.02105
Bupropion XL	Change From Baseline in Hematocrit at the Indicated Time Points	Hematocrit, Follow-up, n=10, 8	-0.0076 Proportion of red blood cells in blood	Standard Deviation 0.04403
Escitalopram	Change From Baseline in Hematocrit at the Indicated Time Points	Hematocrit, Week 8, n=176, 183	-0.0044 Proportion of red blood cells in blood	Standard Deviation 0.02587
Escitalopram	Change From Baseline in Hematocrit at the Indicated Time Points	Hematocrit, Taper, n=13, 16	0.0017 Proportion of red blood cells in blood	Standard Deviation 0.02601
Escitalopram	Change From Baseline in Hematocrit at the Indicated Time Points	Hematocrit, Follow-up, n=10, 8	0.0051 Proportion of red blood cells in blood	Standard Deviation 0.01509

Secondary

Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Hemoglobin, Week 8, n=176, 183	-0.22 Gram per Liter (G/L)	Standard Deviation 7.621
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Hemoglobin, Taper, n=13, 16	-1.54 Gram per Liter (G/L)	Standard Deviation 5.868
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Hemoglobin, Follow-up, n=10, 8	-3.10 Gram per Liter (G/L)	Standard Deviation 12.449
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Total protein, Week 8, n=174, 183	-0.640 Gram per Liter (G/L)	Standard Deviation 5.2784
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Total protein, Taper, n=12, 15	1.197 Gram per Liter (G/L)	Standard Deviation 6.9347
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Total protein, Follow-up, n=8, 12	-4.650 Gram per Liter (G/L)	Standard Deviation 5.5131
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Albumin, Week 8, n=175, 183	-0.254 Gram per Liter (G/L)	Standard Deviation 3.0207
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Albumin, Taper, n=12, 15	-0.086 Gram per Liter (G/L)	Standard Deviation 3.9688
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Albumin, Follow-up, n=8, 12	-1.925 Gram per Liter (G/L)	Standard Deviation 2.0084
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	MCHC, Week 8, n=176, 183	-0.09 Gram per Liter (G/L)	Standard Deviation 8.933
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	MCHC, Taper, n=13, 16	0.54 Gram per Liter (G/L)	Standard Deviation 8.828
Bupropion XL	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	MCHC, Follow-up, n=10, 8	-2.10 Gram per Liter (G/L)	Standard Deviation 9.398
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	MCHC, Taper, n=13, 16	2.25 Gram per Liter (G/L)	Standard Deviation 9.03
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Hemoglobin, Week 8, n=176, 183	-1.16 Gram per Liter (G/L)	Standard Deviation 7.874
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Albumin, Week 8, n=175, 183	-0.678 Gram per Liter (G/L)	Standard Deviation 2.8483
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Hemoglobin, Taper, n=13, 16	1.38 Gram per Liter (G/L)	Standard Deviation 8.057
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	MCHC, Week 8, n=176, 183	0.76 Gram per Liter (G/L)	Standard Deviation 9.821
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Hemoglobin, Follow-up, n=10, 8	0.38 Gram per Liter (G/L)	Standard Deviation 6.163
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Albumin, Taper, n=12, 15	-0.027 Gram per Liter (G/L)	Standard Deviation 4.2372
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Total protein, Week 8, n=174, 183	-0.891 Gram per Liter (G/L)	Standard Deviation 4.0339
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	MCHC, Follow-up, n=10, 8	-2.88 Gram per Liter (G/L)	Standard Deviation 5.055
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Total protein, Taper, n=12, 15	2.000 Gram per Liter (G/L)	Standard Deviation 8.7513
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Albumin, Follow-up, n=8, 12	-1.577 Gram per Liter (G/L)	Standard Deviation 3.6313
Escitalopram	Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	Total protein, Follow-up, n=8, 12	-1.227 Gram per Liter (G/L)	Standard Deviation 4.8619

Secondary

Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Bupropion XL	Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points	MCH, Week 8, n=176, 183	-0.032 Picograms	Standard Deviation 0.7431
Bupropion XL	Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points	MCH, Taper, n=13, 16	0.269 Picograms	Standard Deviation 0.7941
Bupropion XL	Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points	MCH, Follow-up, n=10, 8	-0.050 Picograms	Standard Deviation 1.1909
Escitalopram	Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points	MCH, Week 8, n=176, 183	0.049 Picograms	Standard Deviation 0.7052
Escitalopram	Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points	MCH, Taper, n=13, 16	0.262 Picograms	Standard Deviation 0.7571
Escitalopram	Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points	MCH, Follow-up, n=10, 8	-0.250 Picograms	Standard Deviation 0.4598

Secondary

Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Bupropion XL	Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points	MCV, Week 8, n=176, 183	4.668 Femtoliter	Standard Deviation 62.5158
Bupropion XL	Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points	MCV, Taper, n=13, 16	0.508 Femtoliter	Standard Deviation 2.2291
Bupropion XL	Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points	MCV, Follow-up, n=10, 8	0.320 Femtoliter	Standard Deviation 3.3565
Escitalopram	Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points	MCV, Week 8, n=176, 183	-0.090 Femtoliter	Standard Deviation 2.4759
Escitalopram	Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points	MCV, Taper, n=13, 16	0.181 Femtoliter	Standard Deviation 2.1201
Escitalopram	Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points	MCV, Follow-up, n=10, 8	0.287 Femtoliter	Standard Deviation 1.1205

Secondary

Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8

MADRS is a 10-point rating scale. Each item is scored on a scale of 0-6, with a total score range of 0-60. Higher score indicates worst symptoms. This scale is mainly used to assess the efficacy of antidepressant treatment. The ratings were based on the signs and symptoms during the preceding week prior to the visit. Values at Day0, Week 0 was considered as Baseline value. The observed MADRS total score was considered as missing if any item is missing. Change from Baseline in MADRS was obtained by subtracting the Baseline value from the specific post-Baseline value. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.

Time frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8

Population: PP Population

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Bupropion XL	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-7.0 Scores on a scale	Standard Error 0.47
Bupropion XL	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 196	-15.5 Scores on a scale	Standard Error 0.59
Bupropion XL	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-11.2 Scores on a scale	Standard Error 0.58
Bupropion XL	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-18.6 Scores on a scale	Standard Error 0.57
Bupropion XL	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-3.6 Scores on a scale	Standard Error 0.34
Escitalopram	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	-19.5 Scores on a scale	Standard Error 0.55
Escitalopram	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	-3.8 Scores on a scale	Standard Error 0.33
Escitalopram	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	-8.3 Scores on a scale	Standard Error 0.45
Escitalopram	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	-12.4 Scores on a scale	Standard Error 0.56
Escitalopram	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 196	-16.3 Scores on a scale	Standard Error 0.57

p-value: 0.62795% CI: [-0.7, 1.16]Mixed model repeated measures analysis

p-value: 0.03795% CI: [0.08, 2.66]Mixed model repeated measures analysis

p-value: 0.14395% CI: [-0.4, 2.78]Mixed model repeated measures analysis

p-value: 0.3395% CI: [-0.81, 2.4]Mixed model repeated measures analysis

p-value: 0.27895% CI: [-0.69, 2.4]Mixed model repeated measures analysis

Secondary

Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Bupropion XL	Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points	RBC Count, Taper, n=13, 16	-0.088 10^12 cells per liter	Standard Deviation 0.1599
Bupropion XL	Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points	RBC Count, Week 8, n=176, 183	-0.009 10^12 cells per liter	Standard Deviation 0.2711
Bupropion XL	Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points	RBC Count, Follow-up, n=10, 8	-0.132 10^12 cells per liter	Standard Deviation 0.4018
Escitalopram	Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points	RBC Count, Week 8, n=176, 183	-0.049 10^12 cells per liter	Standard Deviation 0.2563
Escitalopram	Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points	RBC Count, Taper, n=13, 16	-0.007 10^12 cells per liter	Standard Deviation 0.256
Escitalopram	Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points	RBC Count, Follow-up, n=10, 8	0.036 10^12 cells per liter	Standard Deviation 0.1859

Secondary

Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Bupropion XL	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Total bilirubin, Taper, n=12, 15	-3.457 Micromoles per liter (µmol/L)	Standard Deviation 6.5521
Bupropion XL	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Direct bilirubin, Follow-up, n=8, 12	-0.102 Micromoles per liter (µmol/L)	Standard Deviation 1.1192
Bupropion XL	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Direct bilirubin, Week 8, n=175, 180	-0.072 Micromoles per liter (µmol/L)	Standard Deviation 1.3659
Bupropion XL	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Creatinine, Week 8, n=174, 183	7.507 Micromoles per liter (µmol/L)	Standard Deviation 10.6852
Bupropion XL	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Total bilirubin, Follow-up, n=8, 12	0.382 Micromoles per liter (µmol/L)	Standard Deviation 4.0151
Bupropion XL	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Creatinine, Taper, n=12, 15	6.675 Micromoles per liter (µmol/L)	Standard Deviation 6.9134
Bupropion XL	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Direct bilirubin, Taper, n=11, 15	-1.554 Micromoles per liter (µmol/L)	Standard Deviation 3.7607
Bupropion XL	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Creatinine, Follow-up, n=8, 11	4.237 Micromoles per liter (µmol/L)	Standard Deviation 8.9291
Bupropion XL	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Total bilirubin, Week 8, n=175, 181	-0.812 Micromoles per liter (µmol/L)	Standard Deviation 4.7591
Escitalopram	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Creatinine, Follow-up, n=8, 11	1.618 Micromoles per liter (µmol/L)	Standard Deviation 9.6668
Escitalopram	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Total bilirubin, Week 8, n=175, 181	-0.071 Micromoles per liter (µmol/L)	Standard Deviation 4.8022
Escitalopram	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Total bilirubin, Taper, n=12, 15	1.198 Micromoles per liter (µmol/L)	Standard Deviation 3.9442
Escitalopram	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Total bilirubin, Follow-up, n=8, 12	0.338 Micromoles per liter (µmol/L)	Standard Deviation 3.471
Escitalopram	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Direct bilirubin, Week 8, n=175, 180	-0.006 Micromoles per liter (µmol/L)	Standard Deviation 1.231
Escitalopram	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Direct bilirubin, Taper, n=11, 15	0.654 Micromoles per liter (µmol/L)	Standard Deviation 1.7145
Escitalopram	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Direct bilirubin, Follow-up, n=8, 12	0.382 Micromoles per liter (µmol/L)	Standard Deviation 0.907
Escitalopram	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Creatinine, Week 8, n=174, 183	0.307 Micromoles per liter (µmol/L)	Standard Deviation 9.0811
Escitalopram	Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points	Creatinine, Taper, n=12, 15	0.880 Micromoles per liter (µmol/L)	Standard Deviation 10.3281

Secondary

Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	WBC count, Week 8, n=176, 183	-0.032 Giga cells per liter (GI/L)	Standard Deviation 1.6278
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	WBC count, Taper, n=13, 16	0.065 Giga cells per liter (GI/L)	Standard Deviation 1.5513
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	WBC count, Follow-up, n=10, 8	-0.743 Giga cells per liter (GI/L)	Standard Deviation 1.4455
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Total Neutrophils, Week 8, n=176, 183	0.101 Giga cells per liter (GI/L)	Standard Deviation 1.4835
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Total Neutrophils, Taper, n=13, 16	0.306 Giga cells per liter (GI/L)	Standard Deviation 1.6222
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Total Neutrophils, Follow-up, n=10, 8	-0.869 Giga cells per liter (GI/L)	Standard Deviation 1.4578
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Lymphocytes, Week 8, n=176, 183	-0.154 Giga cells per liter (GI/L)	Standard Deviation 0.4833
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Lymphocytes, Taper, n=13, 16	-0.242 Giga cells per liter (GI/L)	Standard Deviation 0.4843
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Lymphocytes, Follow-up, n=10, 8	0.042 Giga cells per liter (GI/L)	Standard Deviation 0.3937
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Basophil, Week 8, n=176, 182	0.001 Giga cells per liter (GI/L)	Standard Deviation 0.0173
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Basophil, Taper, n=13, 16	0.001 Giga cells per liter (GI/L)	Standard Deviation 0.0091
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Basophil, Follow-up, n=10, 8	-0.003 Giga cells per liter (GI/L)	Standard Deviation 0.0163
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Eosinophil, Week 8, n=176, 182	-0.004 Giga cells per liter (GI/L)	Standard Deviation 0.0788
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Eosinophil, Taper, n=13, 16	-0.012 Giga cells per liter (GI/L)	Standard Deviation 0.0592
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Eosinophil, Follow-up, n=10, 8	-0.005 Giga cells per liter (GI/L)	Standard Deviation 0.0627
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Monocyte, Week 8, n=176, 182	0.021 Giga cells per liter (GI/L)	Standard Deviation 0.118
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Monocyte, Taper, n=13, 16	-0.001 Giga cells per liter (GI/L)	Standard Deviation 0.1023
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Monocyte, Follow-up, n=10, 8	0.058 Giga cells per liter (GI/L)	Standard Deviation 0.1292
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Platelet count, Week 8, n=176, 183	7.73 Giga cells per liter (GI/L)	Standard Deviation 32.725
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Platelet count, Taper, n=13, 16	17.15 Giga cells per liter (GI/L)	Standard Deviation 35.126
Bupropion XL	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Platelet count, Follow-up, n=10, 8	28.50 Giga cells per liter (GI/L)	Standard Deviation 35.6
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Basophil, Taper, n=13, 16	0.001 Giga cells per liter (GI/L)	Standard Deviation 0.0131
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	WBC count, Week 8, n=176, 183	-0.073 Giga cells per liter (GI/L)	Standard Deviation 1.6282
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Platelet count, Week 8, n=176, 183	0.56 Giga cells per liter (GI/L)	Standard Deviation 29.492
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	WBC count, Taper, n=13, 16	-0.715 Giga cells per liter (GI/L)	Standard Deviation 1.8547
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Basophil, Follow-up, n=10, 8	-0.012 Giga cells per liter (GI/L)	Standard Deviation 0.0087
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	WBC count, Follow-up, n=10, 8	0.427 Giga cells per liter (GI/L)	Standard Deviation 0.9032
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Monocyte, Taper, n=13, 16	-0.031 Giga cells per liter (GI/L)	Standard Deviation 0.0917
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Total Neutrophils, Week 8, n=176, 183	-0.165 Giga cells per liter (GI/L)	Standard Deviation 1.554
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Eosinophil, Week 8, n=176, 182	0.010 Giga cells per liter (GI/L)	Standard Deviation 0.0899
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Total Neutrophils, Taper, n=13, 16	-0.772 Giga cells per liter (GI/L)	Standard Deviation 1.5656
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Platelet count, Follow-up, n=10, 8	5.38 Giga cells per liter (GI/L)	Standard Deviation 24.784
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Total Neutrophils, Follow-up, n=10, 8	0.424 Giga cells per liter (GI/L)	Standard Deviation 0.747
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Eosinophil, Taper, n=13, 16	0.006 Giga cells per liter (GI/L)	Standard Deviation 0.0488
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Lymphocytes, Week 8, n=176, 183	0.072 Giga cells per liter (GI/L)	Standard Deviation 0.419
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Monocyte, Follow-up, n=10, 8	0.010 Giga cells per liter (GI/L)	Standard Deviation 0.092
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Lymphocytes, Taper, n=13, 16	0.077 Giga cells per liter (GI/L)	Standard Deviation 0.5053
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Eosinophil, Follow-up, n=10, 8	0.019 Giga cells per liter (GI/L)	Standard Deviation 0.0813
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Lymphocytes, Follow-up, n=10, 8	0.022 Giga cells per liter (GI/L)	Standard Deviation 0.4388
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Platelet count, Taper, n=13, 16	7.19 Giga cells per liter (GI/L)	Standard Deviation 22.448
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Basophil, Week 8, n=176, 182	0.002 Giga cells per liter (GI/L)	Standard Deviation 0.0218
Escitalopram	Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points	Monocyte, Week 8, n=176, 182	0.003 Giga cells per liter (GI/L)	Standard Deviation 0.1113

Secondary

Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious AE (SAE)

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants who received any of the study treatment and had any non-serious AE or SAE were considered for analysis. Safety Population comprised of all participants who took at least one dose of the study medication.

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Bupropion XL	Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious AE (SAE)	Any non-serious AE	151 Participants
Bupropion XL	Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious AE (SAE)	Any SAE	10 Participants
Escitalopram	Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious AE (SAE)	Any non-serious AE	150 Participants
Escitalopram	Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious AE (SAE)	Any SAE	11 Participants

Secondary

Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range

ECG was recorded at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). PR interval \<110 or \>220 millisecond (msec); QRS interval \<60 or \>120 msec and corrected QT (QTc) interval \>450 msec were considered as values outside of clinical concern range and were presented as 'High' or 'Low' values. Number of participants with ECG data outside of clinical concern range at any post-Baseline visit are presented. Only those participants with data available at the specified time points were analyzed.

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (NUMBER)
Bupropion XL	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	PR interval, high, Any visit post-randomization	0 Participants
Bupropion XL	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	PR interval, low,Any visit post-randomization	5 Participants
Bupropion XL	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	QRS interval, high, Any visit post-randomization	2 Participants
Bupropion XL	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	QRS interval, low, Any visit post-randomization	0 Participants
Bupropion XL	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	QTc interval, high, Any visit post-randomization	1 Participants
Bupropion XL	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	QTc interval, low, Any visit post-randomization	0 Participants
Escitalopram	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	QTc interval, high, Any visit post-randomization	3 Participants
Escitalopram	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	PR interval, high, Any visit post-randomization	0 Participants
Escitalopram	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	QRS interval, low, Any visit post-randomization	1 Participants
Escitalopram	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	PR interval, low,Any visit post-randomization	2 Participants
Escitalopram	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	QTc interval, low, Any visit post-randomization	0 Participants
Escitalopram	Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range	QRS interval, high, Any visit post-randomization	3 Participants

Secondary

Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)

C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. It consists of 10 items, each with two possible answers (yes/no). Suicidal ideation was interpreted if yes answer at any time during treatment to any one of the five suicidal ideation questions (item 1-5) on the C-SSRS. Suicidal behavior was interpreted if a yes answer at any time during treatment to any one of the five suicidal behavior questions (item 6-10) on the C-SSRS. Suicidal ideation or behavior is interpreted if a yes answer at any time during treatment to any one of the ten suicidal ideation and behavior questions (item 1-10) on the C-SSRS. Number of participants with at least one on-treatment C-SSRS assessment were analyzed. Only those participants with data available at the specified time points were analyzed.

Time frame: Baseline and up to Taper visit (Week 9)

Population: Safety Population

Arm	Measure	Group	Value (NUMBER)
Bupropion XL	Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)	Suicidal Ideation or Behavior	50 Participants
Bupropion XL	Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)	Suicidal Ideation	50 Participants
Bupropion XL	Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)	Suicidal Behavior	2 Participants
Bupropion XL	Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)	Self-Injurious Behavior, no suicidal attempt	1 Participants
Escitalopram	Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)	Self-Injurious Behavior, no suicidal attempt	1 Participants
Escitalopram	Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)	Suicidal Ideation or Behavior	43 Participants
Escitalopram	Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)	Suicidal Behavior	1 Participants
Escitalopram	Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)	Suicidal Ideation	43 Participants

Secondary

Number of Participants With Urinalysis Data Outside the Normal Range

Urine samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Number of participants with urine specific gravity and potential of hydrogen (pH) outside (higher or lower) the normal range are presented. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (NUMBER)
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, low, Follow-up, n=7, 14	2 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, low, Screening, n=265, 266	37 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, high,Screening, n=265, 255	20 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, low,Screening, n=265, 255	1 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity,high, Week 8, n=171, 173	9 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity,low, Week 8, n=171, 173	0 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, high, Taper, n=18, 28	0 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, low, Taper, n=18, 28	0 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, high, Follow-up, n=7, 14	0 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, low, Follow-up, n=7, 14	0 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, high, Screening, n=265, 266	7 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, high, Week 8, n=172, 178	5 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, low, Week 8, n=172, 178	23 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, high, Taper, n=18, 28	0 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, low, Taper, n=18, 28	2 Participants
Bupropion XL	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, high, Follow-up, n=7, 14	0 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, low, Follow-up, n=7, 14	2 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, low, Follow-up, n=7, 14	0 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, high, Taper, n=18, 28	1 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, high,Screening, n=265, 255	12 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, high, Screening, n=265, 266	18 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, low,Screening, n=265, 255	1 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, low, Screening, n=265, 266	28 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity,high, Week 8, n=171, 173	7 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, high, Follow-up, n=7, 14	0 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity,low, Week 8, n=171, 173	1 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, high, Week 8, n=172, 178	9 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, high, Taper, n=18, 28	0 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, low, Taper, n=18, 28	2 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, low, Taper, n=18, 28	1 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine pH, low, Week 8, n=172, 178	20 Participants
Escitalopram	Number of Participants With Urinalysis Data Outside the Normal Range	Urine specific gravity, high, Follow-up, n=7, 14	3 Participants

Secondary

Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range

Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were taken at Screening (within 14 days prior to dosing), randomization visit (Week 0) and at Weeks 1, 2, 4, 6, 8, Taper visit (Week 9) and Follow-up visit (Week 10). SBP \<30 or \>170 millimeter of mercury (mmHg); DBP \<20 or \>110 mmHg and heart rate \<40 or \>120 beats per minute (bpm) were considered as values outside of clinical concern range and were presented as 'High' or 'Low' values. Number of participants with vital signs outside of clinical concern range at any post-Baseline visit are presented. Only those participants with data available at the specified time points were analyzed.

Time frame: Up to Week 10

Population: Safety Population

Arm	Measure	Group	Value (NUMBER)
Bupropion XL	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	SBP, high, Any visit post-Baseline	1 Participants
Bupropion XL	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	SBP, low,Any visit post-Baseline	0 Participants
Bupropion XL	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	DBP, high, Any visit post-Baseline	0 Participants
Bupropion XL	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	DBP, low, Any visit post-Baseline	0 Participants
Bupropion XL	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	HR, high, Any visit post-Baseline	0 Participants
Bupropion XL	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	HR, low, Any visit post-Baseline	0 Participants
Escitalopram	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	HR, high, Any visit post-Baseline	1 Participants
Escitalopram	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	SBP, high, Any visit post-Baseline	0 Participants
Escitalopram	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	DBP, low, Any visit post-Baseline	0 Participants
Escitalopram	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	SBP, low,Any visit post-Baseline	0 Participants
Escitalopram	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	HR, low, Any visit post-Baseline	0 Participants
Escitalopram	Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range	DBP, high, Any visit post-Baseline	0 Participants

Secondary

Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8

For CGI-I rating, the raters indicated their assessment of the participant's total improvement or worsening compared to the participant's condition at the Baseline visit, whether or not the improvement or worsening was thought to be treatment related. Scores ranges from 0 to 7 where 0 represents Not assessed, and the remaining values 1-7 represent Very much improved (1) to Very much worse (7). Participants with score 0 were excluded from analysis. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.

Time frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8

Population: PP Population

Arm	Measure	Group	Value (NUMBER)
Bupropion XL	Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	21.4 Percentage of Participants
Bupropion XL	Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	67.8 Percentage of Participants
Bupropion XL	Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	38.6 Percentage of Participants
Bupropion XL	Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	80.7 Percentage of Participants
Bupropion XL	Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	6 Percentage of Participants
Escitalopram	Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Week 8, n=176, 188	83.5 Percentage of Participants
Escitalopram	Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Week 1, n=184, 199	7.5 Percentage of Participants
Escitalopram	Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Week 2, n=182, 199	22.1 Percentage of Participants
Escitalopram	Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Week 4, n=184, 198	52.5 Percentage of Participants
Escitalopram	Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8	Week 6, n=183, 197	71.6 Percentage of Participants

p-value: 0.54595% CI: [0.35, 1.75]GEE model repeated measures

p-value: 0.82295% CI: [0.58, 1.54]GEE model repeated measures

p-value: 0.00795% CI: [0.38, 0.86]GEE model repeated measures

p-value: 0.41795% CI: [0.54, 1.29]GEE model repeated measures

p-value: 0.48595% CI: [0.49, 1.4]GEE model repeated measures

Secondary

Remission Rate Based on HAMD-17 Total Score

Time frame: Up to Week 8

Population: PP Population

Arm	Measure	Value (NUMBER)
Bupropion XL	Remission Rate Based on HAMD-17 Total Score	39.7 Percentage of Participants
Escitalopram	Remission Rate Based on HAMD-17 Total Score	47.2 Percentage of Participants

p-value: 0.12995% CI: [0.48, 1.1]GEE model

Secondary

Response Rate Based on HAMD-17 Total Score

HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Response was defined as decrease in HAMD-17 total scores at end of acute treatment phase (Week 8) relative to Baseline by at least 50%. Non-responder Imputation was used in calculation of rates.

Time frame: Up to Week 8

Population: PP Population

Arm	Measure	Value (NUMBER)
Bupropion XL	Response Rate Based on HAMD-17 Total Score	69.6 Percentage of Participants
Escitalopram	Response Rate Based on HAMD-17 Total Score	72.9 Percentage of Participants

p-value: 0.47995% CI: [0.55, 1.33]GEE model

Secondary

Sustained Remission Rate Based on HAMD-17 Total Score

HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Sustained remission was defined as remission at end of acute treatment phase and an earlier visit and non-missing HAMD-17 total scores at all visits between these two visits \<=8.

Time frame: Up to Week 8

Population: PP Population

Arm	Measure	Value (NUMBER)
Bupropion XL	Sustained Remission Rate Based on HAMD-17 Total Score	25.5 Percentage of Participants
Escitalopram	Sustained Remission Rate Based on HAMD-17 Total Score	28.6 Percentage of Participants

p-value: 0.48995% CI: [0.54, 1.34]GEE model

Secondary

Sustained Response Rate Based on HAMD-17 Total Score

HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Sustained response was defined as response at end of acute treatment phase and an earlier visit and the decrease from Baseline in non-missing HAMD-17 total scores at all visits between these two visits by at least 40%.

Time frame: Up to Week 8

Population: PP Population

Arm	Measure	Value (NUMBER)
Bupropion XL	Sustained Response Rate Based on HAMD-17 Total Score	51.6 Percentage of Participants
Escitalopram	Sustained Response Rate Based on HAMD-17 Total Score	56.3 Percentage of Participants

p-value: 0.35495% CI: [0.55, 1.24]GEE model

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Study to Evaluate the Efficacy, Safety and Tolerability of Bupropion Hydrochloride Extended-release Tablet, and Escitalopram Oxalate Capsule in Subjects With Major Depressive Disorder

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Study design

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Exclusion criteria

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Secondary

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Baseline characteristics

Adverse events

Outcome results

Mean Change in Hamilton Depression Rating Scale - 17 (HAMD-17) Total Score From Baseline to End of Acute Treatment Phase (Week 8)

Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points

Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points

Change From Baseline in Changes in Sexual Function Questionnaire (CSFQ)

Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8

Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8

Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8

Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8

Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8

Change From Baseline in Hematocrit at the Indicated Time Points

Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points

Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points

Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points

Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8

Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points

Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points

Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points

Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious AE (SAE)

Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range

Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)

Number of Participants With Urinalysis Data Outside the Normal Range

Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range

Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 (Very Much Improved) or 2 (Much Improved) at Weeks 1, 2, 4, 6 and 8

Remission Rate Based on HAMD-17 Total Score

Response Rate Based on HAMD-17 Total Score

Sustained Remission Rate Based on HAMD-17 Total Score

Sustained Response Rate Based on HAMD-17 Total Score