Phase 3
N=534
Study to Evaluate the Efficacy, Safety and Tolerability of Bupropion Hydrochloride Extended-release Tablet, and Escitalopram Oxalate Capsule in Subjects With Major Depressive Disorder
Depressive Disorder, Major
Bottom Line
View on ClinicalTrials.gov: NCT02191397 ↗Enrolled (actual)
534
Serious AEs
3.9%
Results posted
Feb 2019
Primary outcome: Primary: Mean Change in Hamilton Depression Rating Scale - 17 (HAMD-17) Total Score From Baseline to End of Acute Treatment Phase (Week 8) — -14.5; -15.4 Scores on a scale — p=0.139
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Bupropion (Drug); Bupropion Matching Placebo (Drug); Escitalopram (Drug); Escitalopram Matching Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Oct 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change in Hamilton Depression Rating Scale - 17 (HAMD-17) Total Score From Baseline to End of Acute Treatment Phase (Week 8) |
-14.5; -15.4 | 0.139 |
| SECONDARY Response Rate Based on HAMD-17 Total Score |
69.6; 72.9 | 0.479 |
| SECONDARY Remission Rate Based on HAMD-17 Total Score |
39.7; 47.2 | 0.129 |
| SECONDARY Sustained Response Rate Based on HAMD-17 Total Score |
51.6; 56.3 | 0.354 |
| SECONDARY Sustained Remission Rate Based on HAMD-17 Total Score |
25.5; 28.6 | 0.489 |
| SECONDARY Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8 |
-3.6; -3.8; -7.0; -8.3; -11.2; -12.4 | 0.627 |
| SECONDARY Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8 |
-0.4; -0.4; -0.7; -0.8; -1.1; -1.3 | 0.579 |
| 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 |
-1.3; -1.1; -2.0; -2.4; -3.0; -3.4 | 0.358 |
| 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 |
-1.0; -1.0; -1.8; -2.0; -2.9; -3.1 | 0.573 |
| 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 |
-0.6; -0.7; -0.8; -1.2; -1.4; -1.6 | 0.438 |
| SECONDARY Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8 |
-0.3; -0.4; -0.7; -0.8; -1.1; -1.3 | 0.804 |
| 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 |
6; 7.5; 21.4; 22.1; 38.6; 52.5 | 0.545 |
| SECONDARY Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious AE (SAE) |
151; 150; 10; 11 | — |
| SECONDARY Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points |
-0.22; -1.16; -1.54; 1.38; -3.10; 0.38 | — |
| SECONDARY Change From Baseline in Hematocrit at the Indicated Time Points |
0.0016; -0.0044; -0.0051; 0.0017; -0.0076; 0.0051 | — |
| SECONDARY Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points |
-0.032; -0.073; 0.065; -0.715; -0.743; 0.427 | — |
| SECONDARY Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points |
-0.812; -0.071; -3.457; 1.198; 0.382; 0.338 | — |
| 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 |
2.254; 1.315; 7.993; -1.812; -7.337; 5.938 | — |
| SECONDARY Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points |
-0.017; -0.020; -0.019; 0.012; -0.060; -0.060 | — |
| SECONDARY Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points |
-0.032; 0.049; 0.269; 0.262; -0.050; -0.250 | — |
| SECONDARY Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points |
4.668; -0.090; 0.508; 0.181; 0.320; 0.287 | — |
| SECONDARY Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points |
-0.009; -0.049; -0.088; -0.007; -0.132; 0.036 | — |
| SECONDARY Number of Participants With Urinalysis Data Outside the Normal Range |
20; 12; 1; 1; 9; 7 | — |
| SECONDARY Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range |
0; 0; 5; 2; 2; 3 | — |
| SECONDARY Change From Baseline in Changes in Sexual Function Questionnaire (CSFQ) |
3.0; 0.9 | — |
| SECONDARY Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS) |
50; 43; 50; 43; 2; 1 | — |
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.
Eligibility Criteria
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) 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin =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.
Data sourced from ClinicalTrials.gov (NCT02191397). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.