Study In Patients With Depression Not Responding to Selective Serotonin Re-uptake Inhibitors

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00296517
First received: February 23, 2006
Last updated: November 25, 2009
Last verified: November 2009
  Purpose

This study is designed to evaluate the efficacy and safety in depressive patients who did not respond sufficiently to selective serotonin re-uptake inhibitors (SSRI).


Condition Intervention Phase
Major Depressive Disorder (MDD)
Drug: Placebo
Drug: 323U66 (Bupropion Hydrochloride Sustained Release)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clinical Evaluation of 323U66 SR in Patients With Depression - Placebo-controlled, Double-blind, Comparative Study in Patients With Depression Who Did Not Respond Sufficiently to Selective Serotonin Re-uptake Inhibitors

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline in the Hamilton Depression Scale (HAM-D 17 Items) Total Score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hamilton Depression Scale (HAM-D 17 Items) Total Score [ Time Frame: Week 8 and Week 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in the Hamilton Depression Scale (HAM-D 17 Items) Total Score at Week 8 and Total Score at Week 12 [ Time Frame: Baseline to Week 8 and Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Change From Baseline of the Hamilton Depression (HAM-D 17 Items) Total Score at Weeks 8 and 12. [ Time Frame: Baseline to Week 8 and Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Responders Based on Hamilton Depression (HAM-D 17 Items) Scale Total Score at Weeks 8 and 12 [ Time Frame: Baseline to Week 8 and Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Remitters Based on Hamilton Depression (HAM-D 17 Items) Scale Total Score at Weeks 8 and 12 [ Time Frame: Baseline to Week 8 and Week 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in Each Item of the Hamilton Depression Scale (HAM-D 17 Items) Score at Weeks 8 and 12 [ Time Frame: Baseline to Week 8 and Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Change From Baseline in Each Item of the Hamilton Depression Scale (HAM-D 17 Items) Score at Weeks 8 and 12 [ Time Frame: Baseline to Week 8 and Week 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in Clinical Global Impressions - Severity of Illness (CGI-S) Scale at Weeks 1, 2, 3, 4, and 8 and 12 [ Time Frame: Baseline to Weeks 1, 2, 3, 4, 8, and 12 ] [ Designated as safety issue: No ]
  • Percentage of Responders Based on the Clinical Global Impression - Global Improvement (CGI-I) Scale at Weeks 8 and 12 [ Time Frame: Baseline to Week 8 and Week 12 ] [ Designated as safety issue: No ]
  • Study Continuation Rate as Assessed by the Number of Participants at Risk at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Safety: Adverse Events by Organ System Class, Intensity, and Frequency [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]

Enrollment: 325
Study Start Date: January 2006
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects with Major Depressive Disorder who were randomised to placebo to match Bupropion SR during the treatment period.
Drug: Placebo
Subjects with Major Depressive Disorder who were randomised to placebo to match Bupropion SR during the treatment period.
Experimental: Bupropion SR
Subjects with Major Depressive Disorder who were randomized to take 100mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100mg dose of Bupropion morning and evening. Weeks 3 thru 12 received 150mg dose morning and evening. Week 1=dose level 1, 100 mg. Week 2=dose level 2, 200 mg. Weeks 3 - 12=dose level 3, 300 mg.
Drug: 323U66 (Bupropion Hydrochloride Sustained Release)
Subjects with Major Depressive Disorder who were randomized to take 100mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100mg dose of Bupropion morning and evening. Weeks 3 thru 12 received 150mg dose morning and evening. Week 1=dose level 1, 100 mg. Week 2=dose level 2, 200 mg. Weeks 3 - 12=dose level 3, 300 mg.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • [At the start of the pretreatment phase]
  • Target disease: Patients diagnosed as having the following primary disease on the basis of DSM-IV-TR criteria.
  • Major Depressive Disorder, Single Episode (296.2x) (excluding with psychotic features)
  • Major Depressive Disorder, Recurrent (296.3x) (excluding with psychotic features)
  • HAM-D (17 items) total score is >=16.
  • Patients who have been treated with marketed paroxetine (Paxil®) at 20mg/day to 40mg/day for 4 weeks and more at the start of the pretreatment phase.
  • Age: >=18 years old (at the time of informed consent) , <65 years old (at the start of treatment phase )
  • Gender: Male or female.
  • Inpatients or outpatients: Either
  • Informed consent: The subject himself/herself must give written informed consent. However, if the subject is under 20 at the time of giving consent, both the subject himself/herself and his/her legally acceptable representative must give written informed consent.

[At the end of the pretreatment phase]

  1. HAM-D (17 items) total score is ≥14.
  2. Percentage of change from the start of the pretreatment phase in the HAM-D (17 items) total score is <50%

[At the start of the treatment phase]

  1. HAM-D (17 items) total score is ≥14.
  2. Percentage of change from the start of the pretreatment phase in the HAM-D (17 items) total score is <50%

Exclusion Criteria:

[At the start of the pre-treatment phase]

  • Patients with a complication of glaucoma
  • Patients concomitantly using a drug increasing the risk of bleeding and patients with bleeding tendency or predisposition to bleeding
  • Patients with predisposition to seizure (who currently have or have a past history of seizure, febrile convulsive seizure in infancy, cerebral tumour, cerebrovascular disorder or head injury, who have a family history of idiopathic seizure, patients with diabetes who have been treated with oral hypoglycaemics or insulin, or who use drugs lowering the threshold of seizure).
  • Patients who currently have or have a past history of the following disorders:
  • Anorexia nervosa (DSM-IV-TR 307.1)
  • Bulimia nervosa (DSM-IV-TR 307.51)
  • Patients with a history of manic episode
  • Patients with a past or current DSM- IV-TR diagnosis of schizophrenia or other psychotic disorder
  • Patients with a current DSM-IV-TR Axis II diagnosis (e.g., antisocial or borderline personality disorder)
  • Patients starting psychotherapy (except for supportive psychotherapy not aimed at therapeutic efficacy and unlikely to affect efficacy evaluation) and formal cognitive behaviour therapy within 5 weeks prior to the start of the pre-treatment phase
  • Patients with a diagnosis of substance abuse (alcohol or drug) by the DSM-IV-TR criteria or with a diagnosis of substance dependence within 1 year prior to the start of the pre-treatment phase
  • Patients who have received electroconvulsive therapy within 17 weeks prior to the start of the pre-treatment phase
  • Patients who have taken MAO inhibitors (selegiline hydrochloride) within 2 weeks prior to the start of the pre-treatment phase
  • Patients who have taken another investigational drug within 12 weeks prior to the start of the pre-treatment phase
  • Female patients who are pregnant, possibly pregnant or are nursing, and those who want to become pregnant before 30 days after the last dose of the investigational product
  • Patients who have attempted suicide within 17 weeks prior to the start of the pre-treatment phase, or patients for whom the score of suicide-related item No. 3 of HAM-D is >=3, or patients in whom the risk of suicide is judged to be high by the investigator (sub-investigator)
  • Patients in whom the risk of homicide is judged to be high by the investigator (sub-investigator)
  • Patients with a history of hypersensitivity to 323U66 and/or paroxetine
  • Patients with serious cerebral disease
  • Patients who have ECG or clinical evidence of any cardiac condition that the investigator (sub-investigator) feels may predispose the subject to ischemia or arrhythmia
  • Patients with serious physical symptoms (i.e. cardiac/hepatic/renal disorder, hematopoietic disorder) The index of seriousness is Grade 3 of "Criteria for classification of seriousness of adverse drug reactions to pharmaceutical products, etc." (PAB/PSD No.80 in 1992).
  • Patients with a history or complication of cancer or malignant tumour.
  • Patients whose major depressive disorder is due to direct physiological effects of a general medical condition (for example, hypothyroidism, Parkinson's disease, chronic pain)
  • Patients with systolic blood pressure of >=160 mmHg or diastolic blood pressure of >=100 mmHg
  • Patients who are inappropriate for participating in the study in the judgement of the investigator (sub-investigator)

[At the start of the treatment phase]

  1. Patients whose compliance of paroxetine during the pretreatment phase is less than 70%.
  2. Patients who have ECG or clinical evidence of any cardiac condition that the investigator (sub-investigator) feels may predispose the subject to ischemia or arrhythmia
  3. Patients with systolic blood pressure of >=160 mmHg or diastolic blood pressure of >=100 mmHg
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00296517

  Show 65 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00296517     History of Changes
Other Study ID Numbers: AK1102365, 102365
Study First Received: February 23, 2006
Results First Received: March 19, 2009
Last Updated: November 25, 2009
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
bupropion hydrochloride
SSRI
non-responder
depression
placebo-controlled
double-blind
comparative study

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Serotonin
Bupropion
Serotonin Uptake Inhibitors
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014