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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Depressive Disorder

Treatments: Drug: 323U66 (Bupropion Hydrochloride Sustained Release); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00296517

AK1102365

Details and patient eligibility

About

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).

Enrollment: 325 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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325 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Subjects with Major Depressive Disorder who were randomised to placebo to match Bupropion SR during the treatment period.

Treatment:

Drug: Placebo

Bupropion SR

Experimental group

Description:

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.

Treatment:

Drug: 323U66 (Bupropion Hydrochloride Sustained Release)