Paxil Japanese Post Marketing Paediatric Study in Depress... | NCT00812812

Status Module

Label	Type	Description	Intervention Names
paroxetine group	Experimental	paroxetine 10-40mg/day	Drug: paroxetine 10mg tablet Drug: paroxetine 20mg tablet Drug: matched placebo to paroxetine 10mg Drug: matched placebo to paroxetine 20mg
placebo group	Placebo Comparator	matched placebo to paroxetine	Drug: matched placebo to paroxetine 10mg Drug: matched placebo to paroxetine 20mg

Name	Type	Description	Arm Group Labels	Other Names
paroxetine 10mg tablet	Drug	1 or 2 tablet(s) once a day	paroxetine group

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Aichi		445-0064	Japan
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
	Background	GSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing the attached study results summary with a conclusion.

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

ID	Type	URL	Comment
112487	Statistical Analysis Plan	View IPD

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
FG001	Paroxetine	Paroxetine at the initial dose of 10 milligrams (mg) was orally administered once daily for the first 2 weeks of the treatment phase (total of 8 weeks). During the next 6 weeks, paroxetine 10 to 20 mg for participants aged 7 to 11 years or 10 to 40 mg for participants aged 12 to 17 years was orally administered. The dose was up-titrated by one level at a time (an increment of 10 mg/day) at intervals of at least 2 weeks based on clinical judgment. During the taper phase, (0 to 3 weeks), the last dose level in the treatment phase was reduced by 10 mg/day at intervals of 1 week to the final dose level of 10 mg/day.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Full Analysis Set (FAS): all participants who entered the treatment phase, but excluding participants without the target indication, participants who received no tablet of the treatment phase medication, or participants who had no post-baseline CDRS-R data. The analysis was performed on the last observation carried forward (LOCF) dataset.

Posted

Least Squares Mean

Standard Error

scores on a scale

Baseline and Week 8

ID	Title	Description
OG000	Placebo	Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
OG001	Paroxetine	Paroxetine at the initial dose of 10 milligrams (mg) was orally administered once daily for the first 2 weeks of the treatment phase. In the next 6 weeks, paroxetine 10 to 20 mg for participants aged 7 to 11 years or 10 to 40 mg for participants aged 12 to 17 years was orally administered. The dose was up-titrated by one level at a time (an increment of 10 mg/day) at intervals of at least 2 weeks based on clinical judgment. During the taper phase (0 to 3 weeks), the last dose level in the treatment phase was reduced by 10 mg/day at intervals of 1 week to the final dose level of 10 mg/day.

Units	Counts
Participants	OG00027 OG00129

Title

Denominators

Categories

Title	Measurements
	OG000-11.9± 2.54 OG001-16.5± 2.45

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.198		Mean Difference (Net)	-4.6			2-Sided	95	-11.7	2.5			Mean difference was estimated as paroxetine minus placebo.	No	Superiority or Other

Secondary

Change From Baseline in the CDRS-R Total Score at Weeks 1, 2, 3, 4, and 6

FAS. The analysis was performed on the observed case (OC) dataset. Participants whose observation was missing at a particular visit were not included in the analysis for that week.

Posted

Least Squares Mean

Standard Error

scores on a scale

Baseline and Weeks 1, 2, 3, 4, and 6

ID	Title	Description
OG000	Placebo	Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
OG001	Paroxetine	Paroxetine at the initial dose of 10 mg was orally administered once daily for the first 2 weeks of the treatment phase. In the next 6 weeks, paroxetine 10 to 20 mg for participants aged 7 to 11 years or 10 to 40 mg for participants aged 12 to 17 years was orally administered. The dose was up-titrated by one level at a time (an increment of 10 mg/day) at intervals of at least 2 weeks based on clinical judgment. During the taper phase (0 to 3 weeks), the last dose level in the treatment phase was reduced by 10 mg/day at intervals of 1 week to the final dose level of 10 mg/day.

Secondary

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.

FAS. The analysis was performed on the OC dataset. Participants whose observation was missing at a particular visit were not included in the analysis for that week. The analysis of data at Week 8 was also performed on the LOCF dataset.

Posted

Number

participants

Weeks 1, 2, 3, 4, 6, and 8

ID	Title	Description
OG000	Placebo	Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
OG001	Paroxetine	Paroxetine at the initial dose of 10 mg was orally administered once daily for the first 2 weeks of the treatment phase. In the next 6 weeks, paroxetine 10 to 20 mg for participants aged 7 to 11 years or 10 to 40 mg for participants aged 12 to 17 years was orally administered. The dose was up-titrated by one level at a time (an increment of 10 mg/day) at intervals of at least 2 weeks based on clinical judgment. During the taper phase (0 to 3 weeks), the last dose level in the treatment phase was reduced by 10 mg/day at intervals of 1 week to the final dose level of 10 mg/day.

Secondary

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.

Posted

Mean

Standard Deviation

scores on a scale

Baseline and Weeks 1, 2, 3, 4, 6, and 8

ID	Title	Description
OG000	Placebo	Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
OG001	Paroxetine	Paroxetine at the initial dose of 10 mg was orally administered once daily for the first 2 weeks of the treatment phase. In the next 6 weeks, paroxetine 10 to 20 mg for participants aged 7 to 11 years or 10 to 40 mg for participants aged 12 to 17 years was orally administered. The dose was up-titrated by one level at a time (an increment of 10 mg/day) at intervals of at least 2 weeks based on clinical judgment. During the taper phase (0 to 3 weeks), the last dose level in the treatment phase was reduced by 10 mg/day at intervals of 1 week to the final dose level of 10 mg/day.

Secondary

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).

All participants who received paroxetine and 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).

Posted

Mean

Standard Deviation

nanograms per milliliter (ng/mL)

Week 8 or Withdrawal (up to Week 8)

ID	Title	Description
OG000	Paroxetine	Paroxetine at the initial dose of 10 mg was orally administered once daily for the first 2 weeks of the treatment phase. In the next 6 weeks, paroxetine 10 to 20 mg for participants aged 7 to 11 years or 10 to 40 mg for participants aged 12 to 17 years was orally administered. The dose was up-titrated by one level at a time (an increment of 10 mg/day) at intervals of at least 2 weeks based on clinical judgment. During the taper phase (0 to 3 weeks), the last dose level in the treatment phase was reduced by 10 mg/day at intervals of 1 week to the final dose level of 10 mg/day.

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA version 13.1	Systematic Assessment	EG0004 affected27 at risk EG0016 affected29 at risk
Influenza	Infections and infestations	MedDRA version 13.1	Systematic Assessment	EG0002 affected27 at risk EG0011 affected29 at risk
Suicidal ideation	Psychiatric disorders	MedDRA version 13.1	Systematic Assessment	EG0003 affected27 at risk EG0010 affected29 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA version 13.1	Systematic Assessment	EG0002 affected27 at risk EG0011 affected29 at risk
Headache	Nervous system disorders	MedDRA version 13.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected29 at risk

ID	Term
D019964	Mood Disorders
D001523	Mental Disorders

ID	Term
D017374	Paroxetine
D013607	Tablets

ID	Term
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D004304	Dosage Forms
D004364	Pharmaceutical Preparations

ID	Title	Description
BG000	Placebo	Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
BG001	Paroxetine	Paroxetine at the initial dose of 10 milligrams (mg) was orally administered once daily for the first 2 weeks of the treatment phase. In the next 6 weeks, paroxetine 10 to 20 mg for participants aged 7 to 11 years or 10 to 40 mg for participants aged 12 to 17 years was orally administered. The dose was up-titrated by one level at a time (an increment of 10 mg/day) at intervals of at least 2 weeks based on clinical judgment. During the taper phase (0 to 3 weeks), the last dose level in the treatment phase was reduced by 10 mg/day at intervals of 1 week to the final dose level of 10 mg/day.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).			0	27	9	27
EG001	Paroxetine	Paroxetine at the initial dose of 10 mg was orally administered once daily for the first 2 weeks of the treatment phase. In the next 6 weeks, paroxetine 10 to 20 mg for participants aged 7 to 11 years or 10 to 40 mg for participants aged 12 to 17 years was orally administered. The dose was up-titrated by one level at a time (an increment of 10 mg/day) at intervals of at least 2 weeks based on clinical judgment. During the taper phase (0 to 3 weeks), the last dose level in the treatment phase was reduced by 10 mg/day at intervals of 1 week to the final dose level of 10 mg/day.			0	29	9	29