Study to Evaluate the Efficacy, Safety and Tolerability of Bupropion Hydrochloride Extended-release Tablet, and Escitalopram Oxalate Capsule in Subjects With Major Depressive Disorder
CompletedPhase 3Results postedLast updated 25 February 2020
What this trial tests
Phase 3 trial testing Bupropion in Depressive Disorder, Major in 534 participants. Completed in 25 October 2016.
18 and older, any sex, with Depressive Disorder, Major. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Mean Change in Hamilton Depression Rating Scale - 17 (HAMD-17) Total Score From Baseline to End of Acute Treatment Phase (Week 8)Primary· 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 ov
Group
Value
95% CI
Bupropion XL
-14.5
± 0.41
Escitalopram
-15.4
± 0.39
Response Rate Based on HAMD-17 Total ScoreSecondary· 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 t
Group
Value
95% CI
Bupropion XL
69.6
Escitalopram
72.9
Remission Rate Based on HAMD-17 Total ScoreSecondary· 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.
Group
Value
95% CI
Bupropion XL
39.7
Escitalopram
47.2
Sustained Response Rate Based on HAMD-17 Total ScoreSecondary· 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 decr
Group
Value
95% CI
Bupropion XL
51.6
Escitalopram
56.3
Sustained Remission Rate Based on HAMD-17 Total ScoreSecondary· 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-mi
Group
Value
95% CI
Bupropion XL
25.5
Escitalopram
28.6
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8Secondary· 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
Week 1, n=184, 199
Group
Value
95% CI
Bupropion XL
-3.6
± 0.34
Escitalopram
-3.8
± 0.33
Week 2, n=182, 199
Group
Value
95% CI
Bupropion XL
-7.0
± 0.47
Escitalopram
-8.3
± 0.45
Week 4, n=184, 198
Group
Value
95% CI
Bupropion XL
-11.2
± 0.58
Escitalopram
-12.4
± 0.56
Week 6, n=183, 196
Group
Value
95% CI
Bupropion XL
-15.5
± 0.59
Escitalopram
-16.3
± 0.57
Week 8, n=176, 188
Group
Value
95% CI
Bupropion XL
-18.6
± 0.57
Escitalopram
-19.5
± 0.55
Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8Secondary· 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 consid
Week 1, n=184, 199
Group
Value
95% CI
Bupropion XL
-0.4
± 0.04
Escitalopram
-0.4
± 0.04
Week 2, n=182, 199
Group
Value
95% CI
Bupropion XL
-0.7
± 0.06
Escitalopram
-0.8
± 0.05
Week 4, n=184, 198
Group
Value
95% CI
Bupropion XL
-1.1
± 0.06
Escitalopram
-1.3
± 0.06
Week 6, n=183, 197
Group
Value
95% CI
Bupropion XL
-1.5
± 0.06
Escitalopram
-1.6
± 0.06
Week 8, n=176, 188
Group
Value
95% CI
Bupropion XL
-1.9
± 0.06
Escitalopram
-1.9
± 0.06
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 8Secondary· 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 respons
Week 1, n=184, 199
Group
Value
95% CI
Bupropion XL
-1.3
± 0.12
Escitalopram
-1.1
± 0.12
Week 2, n=182, 199
Group
Value
95% CI
Bupropion XL
-2.0
± 0.15
Escitalopram
-2.4
± 0.14
Week 4, n=184, 198
Group
Value
95% CI
Bupropion XL
-3.0
± 0.19
Escitalopram
-3.4
± 0.18
Week 6, n=183, 197
Group
Value
95% CI
Bupropion XL
-4.0
± 0.17
Escitalopram
-4.4
± 0.17
Week 8, n=176, 188
Group
Value
95% CI
Bupropion XL
-4.8
± 0.16
Escitalopram
-5.1
± 0.16
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 8Secondary· 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
Week 1, n=184, 199
Group
Value
95% CI
Bupropion XL
-1.0
± 0.10
Escitalopram
-1.0
± 0.10
Week 2, n=182, 199
Group
Value
95% CI
Bupropion XL
-1.8
± 0.13
Escitalopram
-2.0
± 0.13
Week 4, n=184, 198
Group
Value
95% CI
Bupropion XL
-2.9
± 0.15
Escitalopram
-3.1
± 0.15
Week 6, n=183, 197
Group
Value
95% CI
Bupropion XL
-3.9
± 0.16
Escitalopram
-3.9
± 0.16
Week 8, n=176, 188
Group
Value
95% CI
Bupropion XL
-4.7
± 0.17
Escitalopram
-4.9
± 0.16
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 8Secondary· 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 po
Week 1, n=184, 199
Group
Value
95% CI
Bupropion XL
-0.6
± 0.10
Escitalopram
-0.7
± 0.09
Week 2, n=182, 199
Group
Value
95% CI
Bupropion XL
-0.8
± 0.11
Escitalopram
-1.2
± 0.10
Week 4, n=184, 198
Group
Value
95% CI
Bupropion XL
-1.4
± 0.11
Escitalopram
-1.6
± 0.11
Week 6, n=183, 197
Group
Value
95% CI
Bupropion XL
-1.8
± 0.11
Escitalopram
-2.0
± 0.11
Week 8, n=176, 188
Group
Value
95% CI
Bupropion XL
-2.3
± 0.11
Escitalopram
-2.4
± 0.11
Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8Secondary· 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.
Week 1, n=184, 199
Group
Value
95% CI
Bupropion XL
-0.3
± 0.04
Escitalopram
-0.4
± 0.04
Week 2, n=182, 199
Group
Value
95% CI
Bupropion XL
-0.7
± 0.05
Escitalopram
-0.8
± 0.05
Week 4, n=184, 198
Group
Value
95% CI
Bupropion XL
-1.1
± 0.07
Escitalopram
-1.3
± 0.06
Week 6, n=183, 197
Group
Value
95% CI
Bupropion XL
-1.6
± 0.07
Escitalopram
-1.7
± 0.07
Week 8, n=176, 188
Group
Value
95% CI
Bupropion XL
-2.1
± 0.07
Escitalopram
-2.2
± 0.07
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 8Secondary· 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
Week 1, n=184, 199
Group
Value
95% CI
Bupropion XL
6
Escitalopram
7.5
Week 2, n=182, 199
Group
Value
95% CI
Bupropion XL
21.4
Escitalopram
22.1
Week 4, n=184, 198
Group
Value
95% CI
Bupropion XL
38.6
Escitalopram
52.5
Week 6, n=183, 197
Group
Value
95% CI
Bupropion XL
67.8
Escitalopram
71.6
Week 8, n=176, 188
Group
Value
95% CI
Bupropion XL
80.7
Escitalopram
83.5
Adverse events — posted to ClinicalTrials.gov
Time frame: Adverse events (AEs) were collected from the start of study treatment and until the end safety follow-up visit (up to Week 10). SAEs were recorded from the time the consent form is signed until the follow-up visit (up to Week 10)..
Reporting threshold: 0%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
Bupropion XL
Serious: 10/266 (4%)
Deaths: 1/266
Escitalopram
Serious: 11/268 (4%)
Deaths: 0/268
Serious adverse events (19 terms)
Reaction
System
Bupropion XL
Escitalopram
Depression
Psychiatric disorders
—
—
Blood pressure increased
Investigations
—
—
Brain neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
—
—
Depression suicidal
Psychiatric disorders
—
—
Electrolyte imbalance
Metabolism and nutrition disorders
—
—
Intentional self-injury
Psychiatric disorders
—
—
Lacrimal structure injury
Injury, poisoning and procedural complications
—
—
Major depression
Psychiatric disorders
—
—
Muscle injury
Injury, poisoning and procedural complications
—
—
Overdose
Injury, poisoning and procedural complications
—
—
Radial nerve injury
Injury, poisoning and procedural complications
—
—
Rib fracture
Injury, poisoning and procedural complications
—
—
Somatic symptom disorder
Psychiatric disorders
—
—
Tinnitus
Ear and labyrinth disorders
—
—
Upper respiratory tract infection
Infections and infestations
—
—
Conjunctivitis
Infections and infestations
—
—
Pneumonia
Infections and infestations
—
—
Suicide attempt
Psychiatric disorders
—
—
Urticaria
Skin and subcutaneous tissue disorders
—
—
Other adverse events (166 terms — click to expand)
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.
Publications & conference data
No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.
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Sponsor: as reported to ClinicalTrials.gov by GlaxoSmithKline
Last refreshed: 25 February 2020
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