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

NCT02191397 | Completed Phase 3 Results

• 1 other identifier: 114589
• Study Type: interventional
• Target: 534
• Locations: 1 country
• Sites: 20

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.

Conditions

Depressive Disorder, Major

Keywords

Escitalopram; Major depressive disorder; Non-inferiority; Bupropion

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline (Week 0) and Week 8

Secondary Outcomes (26)

• Response Rate Based on HAMD-17 Total Score

  Up to Week 8

• Remission Rate Based on HAMD-17 Total Score

  Up to Week 8

• Sustained Response Rate Based on HAMD-17 Total Score

  Up to Week 8

• Sustained Remission Rate Based on HAMD-17 Total Score

  Up to Week 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

Study Arms (2)

Bupropion Treatment Arm

EXPERIMENTAL

Subject will receive bupropion in 3 dose levels along with escitalopram matching placebo to maintain the blind in acute treatment phase. At dose level 1 (Week 0 to Week 1), Subjects will receive bupropion XL 150 milligram (mg) per day for a week. At dose level 2 (Week 1 to Week 4), bupropion XL dose will be increased to 300mg/day for further 3 weeks. At dose level 3 (Week 4 to Week 8), bupropion XL dose will be maintained at 300mg/day. Subjects intolerable to dose level 3 will be allowed to down titrate to dose level 2 at anytime, and maintain the dose until the end of acute treatment phase (Week 8, Visit 7). At the end of acute treatment phase, the dose of bupropion XL will be reduced to 150mg/day for 1 week before discontinuation.

Drug: Bupropion; Drug: Escitalopram Matching Placebo

Escitalopram Treatment Arm

ACTIVE COMPARATOR

Subject will receive escitalopram in 3 dose levels along with bupropion matching placebo to maintain the blind in acute treatment phase. At dose level 1 (Week 0 to Week 1), Subjects will receive escitalopram 10mg/day for a week. At dose level 2 (Week 1 to Week 4), escitalopram dose will be maintained at 10mg/day for further 3 weeks. At dose level 3 (Week 4 to Week 8), escitalopram dose will be increased to 20mg/day. Subjects intolerable to dose level 3 will be allowed to down titrate to dose level 2 at anytime, and maintain the dose until the end of acute treatment phase (Week 8, Visit 7). At the end of acute treatment phase, the dose of escitalopram 20mg/day, the dose will be reduced to 10 mg/day for 1 week before discontinuation, while those receiving 10mg/day will discontinuation directly.

Drug: Bupropion Matching Placebo; Drug: Escitalopram

Interventions

Bupropion DRUG

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

Bupropion Treatment Arm

Bupropion Matching Placebo DRUG

Bupropion hydrochloride matching placebo tablets will be supplied to maintain blinding

Escitalopram Treatment Arm

Escitalopram DRUG

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

Escitalopram Treatment Arm

Escitalopram Matching Placebo DRUG

Escitalopram oxalate matching placebo tablets will be supplied to maintain blinding

Bupropion Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (20)

GSK Investigational Site

Guangzhou, Guangdong, 510180, China

Location

GSK Investigational Site

Nanning, Guangxi, 530021, China

Location

GSK Investigational Site

Guiyang, Guizhou, 550004, China

Location

GSK Investigational Site

Baoding, Hebei, 071000, China

Location

GSK Investigational Site

Harbin, Heilongjiang, 150070, China

Location

GSK Investigational Site

Changshacun, Henan, 410011, China

Location

GSK Investigational Site

Changsha, Hunan, China

Location

GSK Investigational Site

Nanjing, Jiangsu, 210029, China

Location

GSK Investigational Site

Xi'an, Shaanxi, 710032, China

Location

GSK Investigational Site

Taiyuan, Shanxi, China

Location

GSK Investigational Site

Xi’an, Shanxi, China

Location

GSK Investigational Site

Kunming, Yunnan, 650032, China

Location

GSK Investigational Site

Hangzhou, Zhejiang, 310003, China

Location

GSK Investigational Site

Beijing, 100083, China

Location

GSK Investigational Site

Beijing, 100088, China

Location

GSK Investigational Site

Beijing, 100096, China

Location

GSK Investigational Site

Guangzhou, 510370, China

Location

GSK Investigational Site

Shanghai, 200030, China

Location

GSK Investigational Site

Shanghai, 200065, China

Location

GSK Investigational Site

Wuhan, China

Location

Related Publications (1)

• Shen Y, Zhao Q, Yu Y, Tan Y, Zhang H, Xu X, Wang Z, Li Y, Hu J, Zhong J, Li H. Efficacy and safety of bupropion hydrochloride extended-release versus escitalopram oxalate in Chinese patients with major depressive disorder: Results from a randomized, double-blind, non-inferiority trial. J Affect Disord. 2019 Oct 1;257:143-149. doi: 10.1016/j.jad.2019.07.023. Epub 2019 Jul 5.

  PMID: 31301615 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Bupropion; Escitalopram

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals; Propylamines; Amines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2014
• First Posted: July 16, 2014
• Study Start: February 10, 2015
• Primary Completion: October 10, 2016
• Study Completion: October 25, 2016
• Last Updated: February 25, 2020
• Results First Posted: February 18, 2019

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

CN (20)