A Fixed Dose Study of 323U66 SR in the Treatment of Major Depressive Disorder (MDD)

NCT01138007 | Completed Phase 3 Results

• 1 other identifier: 113351
• Study Type: interventional
• Target: 572
• Locations: 2 countries
• Sites: 59

Brief Summary

This is a multi-center, placebo-controlled, randomized, double-blind, parallel-comparison study to confirm the efficacy of 323U66 Sustained Release (SR) orally administered to patients with MDD (Major Depressive Disorder) at doses level of 150 mg/day and 300 mg/day for 8 weeks based on the decrease in MADRS (Montgomery-Asberg Depression Rating Scale) total score, and to evaluate the safety based on adverse events, clinical laboratory tests and vital signs.

Conditions

Depressive Disorder, Major

Keywords

Bupropion; 323U66 Sustained Release (SR); MDD (Major Depressive Disorder); IVRS HAM-D; IDS-SR; MADRS

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8/Withdrawal

  The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, Apparent sadness; 2, Reported sadness; 3, Inner tension; 4, Reduced sleep; 5, Reduced appetite; 6, Concentration difficulties; 7, Lassitude; 8, Inability to feel; 9, Pessimistic thoughts; 10, Suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score is 60; 0, no depression; 60, severely depressed. Change from Baseline in the total score was calculated as the value at Week 8/Withdrawal minus the value at Baseline. The least squared means were estimated based on the Analysis of Covariance (ANCOVA) model including Baseline MADRS score and region as covariates.

  Baseline and Week 8/Withdrawal

Secondary Outcomes (8)

• Change From Baseline in the MADRS Total Score at Weeks 1, 2, 4, and 6

  Baseline; Weeks 1, 2, 4, and 6

• Change From Baseline in the MADRS Individual Item Scores at Weeks 1, 2, 4, 6, and 8

  Baseline; Week 1, 2, 4, 6, and 8

• Number of MADRS Responders at Week 8

  Baseline and Week 8

• Number of MADRS Remitters at Week 8

  Week 8

• Number of Clinical Global Impression-Global Improvement (CGI-GI) Responders at Week 8

  Week 8

Study Arms (3)

323U66 SR 150 mg cohort

EXPERIMENTAL

323U66 SR 150 mg tablet is orally administered once in the morning and 323U66 SR 150 mg placebo tablet is orally administered once in the evening throughout the treatment phase.

Drug: 323U66 SR 150 mg tablet; Drug: 323U66 SR 150 mg placebo tablet

323U66 SR 300 mg cohort

EXPERIMENTAL

323U66 SR 150 mg tablet is orally administered once in the morning and 323U66 SR 150 mg placebo tablet is orally administered once in the evening during the first week of the treatment phase. At the second week, 323U66 SR 300mg cohort is up-titrated to a daily dose of 323U66 SR 300 mg, administered as 323U66 SR 150 mg tablet twice daily in the morning and in the evening, and the same daily dose is maintained to administer until the end of the treatment phase.

Drug: 323U66 SR 150 mg tablet; Drug: 323U66 SR 150 mg placebo tablet

Placebo cohort

PLACEBO COMPARATOR

323U66 SR placebo tablet is orally administered twice daily throughout the treatment phase.

Drug: 323U66 SR 150 mg placebo tablet

Interventions

323U66 SR 150 mg tablet DRUG

323U66 SR 150 mg tablet is orally administered once in the morning and/or once in the evening during the teatment phase.

323U66 SR 150 mg cohort; 323U66 SR 300 mg cohort

323U66 SR 150 mg placebo tablet DRUG

323U66 SR 150 mg placebo tablet is orally administered once in the evening and/or once in the morning during the teatment phase.

323U66 SR 150 mg cohort; 323U66 SR 300 mg cohort; Placebo cohort

Eligibility Criteria

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

You may qualify if:

• \[At the start time of the run-in phase\]
• Subject must have a primary diagnosis of major depressive disorder as classified by the DSM-IV-TR criteria as below (however, to exclude those accompanied by comorbid psychiatric disorders), and be showing currently a symptom of depression or depressive status: Major depressive disorder, single episode (296.2x); Major depressive disorder, recurrent (296.3x).
• Subject must have a total score of \>=20 on the IVRS HAM-D (17 items).
• Subject must have a total score of \>=25 on the IDS-SR.
• Subject must have a score of \>=1 on 4 out 5 items on the 5-item subscale of the IDS-SR (Item 19, 20, 21, 22 and 30), and a total score of \>=7 on the 5-item subscale of the IDS-SR.
• Subject must have a CGI-SI score of \>=4 (i.e., Moderately ill or much worse).
• Subject must have the current depressive episode's duration of \>=8 weeks but \<24 months.
• Subject is outpatient.
• Subject must show QTc \<450 millisecond (msec) or \<480msec with Bundle Branch Block - values based on either single ECG values or triplicate ECG averaged QTc values obtained over a brief recording period.
• Subject must show a value less than twice of the upper limit of normal value range of AST (GOT) and ALT (GPT), and a value \<=1.5 times of the upper limit of normal value range of both Al-P and total bilirubin (however, subject who shows \>35% of direct bilirubin with a value \>=1.5 times of the upper limit of normal range of total bilirubin regards eligible).
• Subject must read and write at a level sufficient to provide written informed consent prior to study participation and complete study-related materials. If subject is \<20 years of age at the time of giving consent, both the subject himself / herself and his / her proxy consenter must give written informed consent.
• \[At the start time of the treatment phase\]
• Subject must have a total score of \>=20 of the IVRS-based HAM-D (17 items).
• Subject whose IVRS HAM-D (17 items) total score has not been increased or decreased by \>25% during the run-in phase.
• Subject must have a total score of \>=25 on the IDS-SR.

You may not qualify if:

• \[At the start time of Run-in phase (Visit 1)\]
• Subject has predispositions to seizure: who currently has or has a past history of seizure or seizure disorder, more than a single febrile seizure in infancy, cerebral tumour, or head / brain injury (traumatic); who has a family history of idiopathic seizure; who is diabetic patient with treating by oral hypoglycaemics or insulin; who uses drugs lowering the threshold of seizure.
• Subject has a history or current diagnosis of anorexia nervosa (DSM-IV-TR 307.1) or bulimia (DSM-IV-TR 307.51).
• Subject has a primary DSM-IV diagnosis of, or received treatment for, panic disorder, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), or acute stress disorder within 12 months before the start time of Run-in phase.
• Subject has a DSM-IV diagnosis of schizophrenia, or other psychotic disorder(s) including bipolar disorder.
• Subject has a history of or currently has manic episode(s).
• Subject has any other DSM-IV axis II diagnosis that would suggest non-responsiveness to pharmacotherapy or non-compliance with the protocol (e.g., antisocial, borderline disorder or narcissistic personality disorder).
• Subject starting psychotherapy (except for supportive psychotherapy not aimed at therapeutic efficacy and unlikely to affect efficacy evaluation) or a cognitive behaviour therapy within 12 weeks before start time of the run-in phase.
• Subject received electroconvulsive therapy (ECT) within 24 weeks before start time of the run-in phase.
• Subject took MAO inhibitors (selegiline hydrochloride) within 2 weeks before start time of the run-in phase.
• Subject who has undergone treatment with a depot neuroleptic in the past.
• Subject has systolic blood pressure of \>=160 mmHg or diastolic pressure of \>=100 mmHg.
• Subject 1) is possibly pregnant, 2) is pregnant, lactating, or 3) does not agree to use contraceptive method(s) specified in the protocol to avoid pregnancy during the study (females only). Or subject wants to become pregnant during the study (females only).
• Subject has a history of alcohol / substance abuse or dependence within 12 months before start time of the run-in phase and/or has a positive result in a urine test for illicit drug use at start time of the run-in phase.
• Subject, who in the opinion of the investigator (or sub-investigator), poses a current serious suicidal risk or has made a suicide attempt within the past 6 months.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (59)

GSK Investigational Site

Aichi, 470-1141, Japan

Location

GSK Investigational Site

Aichi, 479-0837, Japan

Location

GSK Investigational Site

Fukuoka, 802-0006, Japan

Location

GSK Investigational Site

Fukuoka, 810-0001, Japan

Location

GSK Investigational Site

Fukuoka, 810-0004, Japan

Location

GSK Investigational Site

Fukuoka, 810-0022, Japan

Location

GSK Investigational Site

Fukuoka, 812-0011, Japan

Location

GSK Investigational Site

Fukuoka, 815-0041, Japan

Location

GSK Investigational Site

Fukushima, 960-0102, Japan

Location

GSK Investigational Site

Fukushima, 961-0021, Japan

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GSK Investigational Site

Fukushima, 963-0207, Japan

Location

GSK Investigational Site

Hiroshima, 731-0121, Japan

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GSK Investigational Site

Hyōgo, 673-0891, Japan

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GSK Investigational Site

Ibaraki, 311-3193, Japan

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GSK Investigational Site

Kanagawa, 214-0014, Japan

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GSK Investigational Site

Kanagawa, 221-0835, Japan

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GSK Investigational Site

Kanagawa, 231-0023, Japan

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GSK Investigational Site

Kanagawa, 244-0816, Japan

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GSK Investigational Site

Kanagawa, 251-0055, Japan

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GSK Investigational Site

Kumamoto, 861-8002, Japan

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GSK Investigational Site

Kyoto, 616-8421, Japan

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GSK Investigational Site

Nara, 639-0225, Japan

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GSK Investigational Site

Osaka, 545-0001, Japan

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GSK Investigational Site

Osaka, 573-0032, Japan

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GSK Investigational Site

Osaka, 576-0054, Japan

Location

GSK Investigational Site

Osaka, 589-0011, Japan

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GSK Investigational Site

Osaka, 596-0076, Japan

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GSK Investigational Site

Saga, 842-0192, Japan

Location

GSK Investigational Site

Saga, 843-0023, Japan

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GSK Investigational Site

Saga, 847-0053, Japan

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GSK Investigational Site

Saitama, 341-0018, Japan

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GSK Investigational Site

Shizuoka, 420-0839, Japan

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GSK Investigational Site

Tochigi, 321-0953, Japan

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GSK Investigational Site

Tokyo, 102-0071, Japan

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GSK Investigational Site

Tokyo, 110-0003, Japan

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GSK Investigational Site

Tokyo, 125-0041, Japan

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GSK Investigational Site

Tokyo, 141-0021, Japan

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GSK Investigational Site

Tokyo, 142-0051, Japan

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GSK Investigational Site

Tokyo, 150-0001, Japan

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GSK Investigational Site

Tokyo, 151-0053, Japan

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GSK Investigational Site

Tokyo, 154-0004, Japan

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GSK Investigational Site

Tokyo, 154-0012, Japan

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GSK Investigational Site

Tokyo, 160-0022, Japan

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GSK Investigational Site

Tokyo, 160-0023, Japan

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GSK Investigational Site

Tokyo, 164-0012, Japan

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GSK Investigational Site

Tokyo, 166-0011, Japan

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GSK Investigational Site

Tokyo, 170-0002, Japan

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GSK Investigational Site

Tokyo, 173-0004, Japan

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GSK Investigational Site

Tokyo, 180-0005, Japan

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GSK Investigational Site

Gyeonggi-do, 431-070, South Korea

Location

GSK Investigational Site

Incheon, 405-760, South Korea

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GSK Investigational Site

Seoul, 110-746, South Korea

Location

GSK Investigational Site

Seoul, 135-710, South Korea

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GSK Investigational Site

Seoul, 136-705, South Korea

Location

GSK Investigational Site

Seoul, 137-701, South Korea

Location

GSK Investigational Site

Seoul, 138-736, South Korea

Location

GSK Investigational Site

Seoul, 143-729, South Korea

Location

GSK Investigational Site

Seoul, 150-713, South Korea

Location

GSK Investigational Site

Seoul, 156-707, South Korea

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Tablets

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

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: June 3, 2010
• First Posted: June 7, 2010
• Study Start: June 17, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 7, 2012
• Last Updated: August 10, 2018
• Results First Posted: May 6, 2013

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

JP (49); KR (10)