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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02191397
• Date of registration: 14/07/2014
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Study to Evaluate the Efficacy, Safety and Tolerability of Bupropion Hydrochloride Extended-release Tablet, and Escitalopram Oxalate Capsule in Subjects With Major Depressive Disorder
• Scientific title: 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
• Date of first enrolment: February 10, 2015
• Target sample size: 534
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02191397
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

China

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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) <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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Depressive Disorder, Major

Intervention(s)

Drug: Bupropion

Drug: Bupropion Matching Placebo

Drug: Escitalopram

Drug: Escitalopram Matching Placebo

Primary Outcome(s)

Mean Change in Hamilton Depression Rating Scale - 17 (HAMD-17) Total Score From Baseline to End of Acute Treatment Phase (Week 8) [Time Frame: Baseline (Week 0) and Week 8]

Secondary Outcome(s)

Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points [Time Frame: Up to Week 10]

Number of Participants With Urinalysis Data Outside the Normal Range [Time Frame: Up to Week 10]

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 [Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8]

Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points [Time Frame: Up to Week 10]

Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8 [Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8]

Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS) [Time Frame: Baseline and up to Taper visit (Week 9)]

Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points [Time Frame: Up to Week 10]

Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8 [Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8]

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]

Sustained Remission Rate Based on HAMD-17 Total Score [Time Frame: Up to Week 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 [Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8]

Response Rate Based on HAMD-17 Total Score [Time Frame: Up to Week 8]

Sustained Response Rate Based on HAMD-17 Total Score [Time Frame: Up to Week 8]

Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8 [Time Frame: Baseline (Week 0) and 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 [Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 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 [Time Frame: Up to Week 10]

Change From Baseline in Changes in Sexual Function Questionnaire (CSFQ) [Time Frame: Baseline (Day 0) and Week 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 [Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8]

Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points [Time Frame: Up to Week 10]

Remission Rate Based on HAMD-17 Total Score [Time Frame: Up to Week 8]

Change From Baseline in Hematocrit at the Indicated Time Points [Time Frame: Up to Week 10]

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]

Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious AE (SAE) [Time Frame: Up to Week 10]

Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range [Time Frame: Up to Week 10]

Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points [Time Frame: Up to Week 10]

Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range [Time Frame: Up to Week 10]

Secondary ID(s)

114589

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/02/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02191397