Paxil Japanese Post Marketing Paediatric Study in Depression (Double-blind, Placebo Controlled Study)

Study Overview
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Brief Summary
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This study is designed to compare the efficacy of oral paroxetine 10 to 40 mg/day (initial dose:10 mg/day) versus placebo administered once daily (after evening meal) for 8 weeks in children and adolescents with major depressive disorder (MDD) based on the change from baseline to Week 8/end-of-study in the CDRS-R total score in a randomized, double-blind, placebo-controlled parallel-group study.

Official Title
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A Randomised, Double-blind, Placebo Controlled, Parallel Group , Flexible Dose Study to Evaluate the Efficacy and Safety of Paxil® Tablets in Children and Adolescents With Major Depressive Disorder<Post-marketing Clinical Study>

Conditions
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Depressive Disorder

Intervention / Treatment
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* Drug: paroxetine 10mg tablet
* Drug: paroxetine 20mg tablet
* Drug: matched placebo to paroxetine 10mg
* Drug: matched placebo to paroxetine 20mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: run-in period: A subject will be considered eligible for the study only if all of the following criteria apply at start of placebo run-in period. Patients who are diagnosed with the following depressive disorders according to the DSM-IV-TR criteria, and currently presents with a depressive episodes. Depressive disorders: MDD, single episode (296.2), MDD, recurrent (296.3) 7 years and older and under 18 years old (at the time of consent obtained) Patients with a total raw summary score on the CDRS-R of 45 or greater at the Week -2 visit. Patients whose legally acceptable representative (e.g., caretaker, custodian) is able to give written consent to participation to this study. Patients aged 12 and above at the time of consent obtained should be able to sign the informed consent on one's own. Efforts should be exerted in obtaining the informed assent in writing from patients aged less than 12. Patients with ideal body weight +/- 2SD Gender: Male or female treatment period: Subjects who meet the following criteria at Week 0 (Baseline) may be progressed to the Treatment period: - Patients with a total raw summary score on the CDRS-R at Week 0 visit of 45 or greater. Exclusion Criteria run-in period: A subject will not be eligible for inclusion to this study if any of the following criteria applies at start of run-in period: Patients who in the investigator's judgment presented with a clinically predominant Axis I disorder other than MDD (e.g. dysthymic disorder, eating disorders, Specific phobia, PTSD, OCD, Panic disorder, etc) Patients with any history of a psychotic episode or psychotic disorder (including schizophrenia ), or complication of these diseases. Patients with a history of a bipolar disorder, or complication of these diseases. Patients with Attention-Deficit, or Hyperactivity Disorder Patients with Mental Retardation or Pervasive Development Disorder Patients diagnosed with Substance Abuse or Dependence within 12 weeks prior to the Screening visit Patients with past treatment experience with the investigational drug (i.e. paroxetine) Patients treated with electroconvulsive therapy in the immediate 12 weeks prior to the Screening visit Patients with past history of serotonin syndrome and neuroleptic malignant syndrome. Patients with CDRS-R score of suicidal ideation of 3 or greater. Or patients whose C-SSRS assessment suggests that they are or have been at significant risk for harming themselves or have actually harmed themselves, or who, in the opinion of the chief investigator (subinvestigator), are at significant risk for harming self. Patients with past history of suicide attempt, self harm(excluding no suicidal intent  ), or an intentional overdose (excluding obviously unintentional overdose) Patients who have been treated with other clinical trial investigational drug (including post-marketing clinical trial) in the immediate past 3 months of the Week -2 visit. Patients who have taken antidepressant medication 1 week prior to screening. Patients with complicated disease of glaucoma. Patients with convulsive disorders such as epilepsy or past history of these diseases. Patients regularly using drugs (e.g. NSAIDs) that would increase the risk of haemorrhage, or patients with bleeding tendency or haemorrhagic diathesis. Patients with severe renal and hepatic disorder. Patients with serious organic disorder in the brain. Patients with chronic hepatitis type B and/or C which is positive of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibody. Patients with a current history of carcinoma or malignant tumor, or complication of these diseases. Female patients who are pregnant, lactating, or who might be pregnant, or who wish to be pregnant during the study period Patients in the opinion of the chief investigator (subinvestigator) judged as not eligible for the study. Patients with clinical significant comorbid impulsivity symptoms.(e.g. Personality Disorder, Conduct Disorder) treatment period: Subjects for whom any of the following categories apply at Week 0 (start of the treatment period) will not be progressed to the treatment phase. Patients with CDRS-R score of suicidal ideation of 3 or greater, or patients who, in the opinion of the chief investigator (sub investigator), are at significant risk for harming self Patients with variation of the CDRS-R total raw summary score at Week 0 of +/-25% or greater compared to that of Week -2. Patients with drug compliance of Drug 1 (run-in placebo) from Week -2 to Week 0 less than 80%. Patients, in the opinion of the chief investigator (sub investigator) judged as not appropriate for the study.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: paroxetine group<br>paroxetine 10-40mg/day | Drug: paroxetine 10mg tablet<br>* 1 or 2 tablet(s) once a day<br>* Other names: Paxil;Drug: paroxetine 20mg tablet<br>* 1 tablet once a day<br>* Other names: Paxil;Drug: matched placebo to paroxetine 10mg<br>* 2 tablets once a day<br>Drug: matched placebo to paroxetine 20mg<br>* 1 tablet once a day<br>|
| Placebo Comparator: placebo group<br>matched placebo to paroxetine | Drug: matched placebo to paroxetine 10mg<br>* 2 tablets once a day<br>Drug: matched placebo to paroxetine 20mg<br>* 1 tablet once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Children's Depression Rating Scale -Revised (CDRS-R) Total Score at Week 8 | The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 questions. Each question is graded on a 5- or 7-point scale. The highest possible score is 113 (the most severe measure of depression), and the lowest is 17 (not suffering from depression). CDRS-R scores were assessed by the investigator. The change from Baseline in the CDRS-R total score was calculated as the total score at Week 8 minus the total score at Baseline. The data were adjusted with the total score at Baseline. | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the CDRS-R Total Score at Weeks 1, 2, 3, 4, and 6 | The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 questions. Each question is graded on a 5- or 7-point scale. The highest possible score is 113 (the most severe measure of depression), and the lowest is 17 (not suffering from depression). CDRS-R scores were assessed by the investigator. The change from Baseline in the CDRS-R total score was calculated as the total score at Week 8 minus the total score at Baseline. The data were adjusted with the total score at Baseline. | Baseline and Weeks 1, 2, 3, 4, and 6 | 
| Number of Clinical Global Impression - Global Improvement (CGI-GI) Responders at Weeks 1, 2, 3, 4, 6, and 8 | CGI-GI is assessed on an 8-grade scale: 0, not assessed; 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; and 7, very much worse. CGI-GI was assessed by the investigator. Participants who were rated as 1 (very much improved) or 2 (much improved) were categorized as CGI-GI responders. | Weeks 1, 2, 3, 4, 6, and 8 | 
| Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-SI) Score at Weeks 1, 2, 3, 4, 6, and 8 | CGI-SI is assessed on an 8-grade scale: 0, not assessed; 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; and 7, among the most extremely ill. CGI-SI was assessed by the investigator. The change from Baseline in CGI-SI score was calculated as the score at Weeks 1, 2, 3, 4, 6, and 8 minus the score at Baseline. | Baseline and Weeks 1, 2, 3, 4, 6, and 8 | 
| Plasma Paroxetine Concentrations at 12 Hours and 24 Hours After Administration of Study Drug at Week 8 or Withdrawal | Summary statistics for the plasma paroxetine concentrations at each time point were calculated by the dosage just before blood sampling using data from participants in whom plasma samples were collected at either 12 hours (plus or minus 2 hours) or 24 hours (plus or minus 2 hours) after the last administration of the study drug at Week 8 or Withdrawal (up to Week 8). | Week 8 or Withdrawal (up to Week 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDRS-R, paroxetine, selective serotonin reuptake inhibitor, children and adolescents