Clinical trial NCT00296517: Study In Patients With Depression Not Responding to Selective Serotonin Re-uptake Inhibitors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depressive Disorder
Keywords: depression
double-blind
placebo-controlled
bupropion hydrochloride
SSRI
comparative study
non-responder
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-02-27
Enrollment: 325
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility 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

Primary outcomes:
measure: Change From Baseline in the Hamilton Depression Scale (HAM-D 17 Items) Total Score
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Hamilton Depression Scale (HAM-D 17 Items) Total Score
timeFrame: Week 8 and Week 12
measure: Change From Baseline in the Hamilton Depression Scale (HAM-D 17 Items) Total Score at Week 8 and Total Score at Week 12
timeFrame: Baseline to Week 8 and Week 12
measure: Percentage of Change From Baseline of the Hamilton Depression (HAM-D 17 Items) Total Score at Weeks 8 and 12.
timeFrame: Baseline to Week 8 and Week 12
measure: Percentage of Responders Based on Hamilton Depression (HAM-D 17 Items) Scale Total Score at Weeks 8 and 12
timeFrame: Baseline to Week 8 and Week 12
measure: Percentage of Remitters Based on Hamilton Depression (HAM-D 17 Items) Scale Total Score at Weeks 8 and 12
timeFrame: Baseline to Week 8 and Week 12
measure: Change From Baseline in Each Item of the Hamilton Depression Scale (HAM-D 17 Items) Score at Weeks 8 and 12
timeFrame: Baseline to Week 8 and Week 12
measure: Percentage of Change From Baseline in Each Item of the Hamilton Depression Scale (HAM-D 17 Items) Score at Weeks 8 and 12
timeFrame: Baseline to Week 8 and Week 12
measure: Change From Baseline in Clinical Global Impressions - Severity of Illness (CGI-S) Scale at Weeks 1, 2, 3, 4, and 8 and 12
timeFrame: Baseline to Weeks 1, 2, 3, 4, 8, and 12
measure: Percentage of Responders Based on the Clinical Global Impression - Global Improvement (CGI-I) Scale at Weeks 8 and 12
timeFrame: Baseline to Week 8 and Week 12
measure: Study Continuation Rate as Assessed by the Number of Participants at Risk at Week 12
timeFrame: Week 12
measure: Safety: Adverse Events by Organ System Class, Intensity, and Frequency
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukushima
country: Japan
facility: GSK Investigational Site
city: Fukushima
country: Japan
facility: GSK Investigational Site
city: Fukushima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ishikawa
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Nara
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tottori
country: Japan
facility: GSK Investigational Site
city: Tottori
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: