Trial Outcomes & Findings for Paxil Japanese Post Marketing Paediatric Study in Depression (Double-blind, Placebo Controlled Study) (NCT NCT00812812)
NCT ID: NCT00812812
Last Updated: 2017-01-13
Results Overview
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.
TERMINATED
PHASE4
56 participants
Baseline and Week 8
2017-01-13
Participant Flow
This study consisted of 3 phases: a 2-week placebo run-in phase, an 8-week treatment phase, and a 0- to 3-week taper phase. In the run-in phase, placebo was administered once daily for 2 weeks. In the treatment phase, paroxetine or placebo was orally administered once daily for 8 weeks. In the taper phase, the dose was gradually reduced.
Participant milestones
| Measure |
Placebo
Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
27
|
29
|
|
Overall Study
COMPLETED
|
24
|
25
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
| Measure |
Placebo
Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
Baseline Characteristics
Paxil Japanese Post Marketing Paediatric Study in Depression (Double-blind, Placebo Controlled Study)
Baseline characteristics by cohort
| Measure |
Placebo
n=27 Participants
Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
|
Paroxetine
n=29 Participants
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.
|
Total
n=56 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
14.8 Years
STANDARD_DEVIATION 2.62 • n=5 Participants
|
14.4 Years
STANDARD_DEVIATION 1.99 • n=7 Participants
|
14.6 Years
STANDARD_DEVIATION 2.30 • n=5 Participants
|
|
Gender
Female
|
18 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Gender
Male
|
9 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
|
27 participants
n=5 Participants
|
29 participants
n=7 Participants
|
56 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 8Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=27 Participants
Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
|
Paroxetine
n=29 Participants
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.
|
|---|---|---|
|
Change From Baseline in the Children's Depression Rating Scale -Revised (CDRS-R) Total Score at Week 8
|
-11.9 scores on a scale
Standard Error 2.54
|
-16.5 scores on a scale
Standard Error 2.45
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, and 6Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=27 Participants
Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
|
Paroxetine
n=29 Participants
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.
|
|---|---|---|
|
Change From Baseline in the CDRS-R Total Score at Weeks 1, 2, 3, 4, and 6
Week 1, n=27, 29
|
-4.6 scores on a scale
Standard Error 1.10
|
-5.4 scores on a scale
Standard Error 1.06
|
|
Change From Baseline in the CDRS-R Total Score at Weeks 1, 2, 3, 4, and 6
Week 2, n=26, 29
|
-4.9 scores on a scale
Standard Error 1.56
|
-8.8 scores on a scale
Standard Error 1.48
|
|
Change From Baseline in the CDRS-R Total Score at Weeks 1, 2, 3, 4, and 6
Week 3, n=24, 28
|
-10.6 scores on a scale
Standard Error 1.90
|
-12.0 scores on a scale
Standard Error 1.76
|
|
Change From Baseline in the CDRS-R Total Score at Weeks 1, 2, 3, 4, and 6
Week 4, n=25, 27
|
-12.5 scores on a scale
Standard Error 2.24
|
-14.6 scores on a scale
Standard Error 2.15
|
|
Change From Baseline in the CDRS-R Total Score at Weeks 1, 2, 3, 4, and 6
Week 6, n=24, 26
|
-14.2 scores on a scale
Standard Error 2.21
|
-15.7 scores on a scale
Standard Error 2.12
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, and 8Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=27 Participants
Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
|
Paroxetine
n=29 Participants
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.
|
|---|---|---|
|
Number of Clinical Global Impression - Global Improvement (CGI-GI) Responders at Weeks 1, 2, 3, 4, 6, and 8
Week 1, n=27, 29
|
4 participants
|
4 participants
|
|
Number of Clinical Global Impression - Global Improvement (CGI-GI) Responders at Weeks 1, 2, 3, 4, 6, and 8
Week 2, n=26, 29
|
4 participants
|
7 participants
|
|
Number of Clinical Global Impression - Global Improvement (CGI-GI) Responders at Weeks 1, 2, 3, 4, 6, and 8
Week 3, n=24, 28
|
7 participants
|
9 participants
|
|
Number of Clinical Global Impression - Global Improvement (CGI-GI) Responders at Weeks 1, 2, 3, 4, 6, and 8
Week 4, n=25, 27
|
13 participants
|
12 participants
|
|
Number of Clinical Global Impression - Global Improvement (CGI-GI) Responders at Weeks 1, 2, 3, 4, 6, and 8
Week 6, n=24, 26
|
12 participants
|
13 participants
|
|
Number of Clinical Global Impression - Global Improvement (CGI-GI) Responders at Weeks 1, 2, 3, 4, 6, and 8
Week 8 (OC), n=24, 25
|
11 participants
|
14 participants
|
|
Number of Clinical Global Impression - Global Improvement (CGI-GI) Responders at Weeks 1, 2, 3, 4, 6, and 8
Week 8 (LOCF), n=27, 29
|
11 participants
|
15 participants
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 6, and 8Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=27 Participants
Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
|
Paroxetine
n=29 Participants
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.
|
|---|---|---|
|
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-SI) Score at Weeks 1, 2, 3, 4, 6, and 8
Week 1, n=27, 29
|
-0.1 scores on a scale
Standard Deviation 0.32
|
-0.2 scores on a scale
Standard Deviation 0.41
|
|
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-SI) Score at Weeks 1, 2, 3, 4, 6, and 8
Week 2, n=26, 29
|
-0.1 scores on a scale
Standard Deviation 0.48
|
-0.5 scores on a scale
Standard Deviation 0.69
|
|
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-SI) Score at Weeks 1, 2, 3, 4, 6, and 8
Week 3, n=24, 28
|
-0.3 scores on a scale
Standard Deviation 0.62
|
-0.6 scores on a scale
Standard Deviation 0.57
|
|
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-SI) Score at Weeks 1, 2, 3, 4, 6, and 8
Week 4, n=25, 27
|
-0.5 scores on a scale
Standard Deviation 0.82
|
-0.7 scores on a scale
Standard Deviation 0.76
|
|
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-SI) Score at Weeks 1, 2, 3, 4, 6, and 8
Week 6, n=24, 26
|
-0.5 scores on a scale
Standard Deviation 0.66
|
-0.8 scores on a scale
Standard Deviation 0.82
|
|
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-SI) Score at Weeks 1, 2, 3, 4, 6, and 8
Week 8 (OC), n=24, 25
|
-0.5 scores on a scale
Standard Deviation 0.72
|
-1.0 scores on a scale
Standard Deviation 0.89
|
|
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-SI) Score at Weeks 1, 2, 3, 4, 6, and 8
Week 8 (LOCF), n=27, 29
|
-0.4 scores on a scale
Standard Deviation 0.75
|
-0.9 scores on a scale
Standard Deviation 0.88
|
SECONDARY outcome
Timeframe: Week 8 or Withdrawal (up to Week 8)Population: 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).
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).
Outcome measures
| Measure |
Placebo
n=18 Participants
Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
|
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.
|
|---|---|---|
|
Plasma Paroxetine Concentrations at 12 Hours and 24 Hours After Administration of Study Drug at Week 8 or Withdrawal
paroxetine 10 mg, 12 hours, n=4
|
4.4683 nanograms per milliliter (ng/mL)
Standard Deviation 2.16507
|
—
|
|
Plasma Paroxetine Concentrations at 12 Hours and 24 Hours After Administration of Study Drug at Week 8 or Withdrawal
paroxetine 10 mg, 24 hours, n=3
|
8.9713 nanograms per milliliter (ng/mL)
Standard Deviation 7.81518
|
—
|
|
Plasma Paroxetine Concentrations at 12 Hours and 24 Hours After Administration of Study Drug at Week 8 or Withdrawal
paroxetine 20 mg, 12 hours, n=1
|
49.5820 nanograms per milliliter (ng/mL)
Standard Deviation 0
|
—
|
|
Plasma Paroxetine Concentrations at 12 Hours and 24 Hours After Administration of Study Drug at Week 8 or Withdrawal
paroxetine 20 mg, 24 hours, n=3
|
18.2713 nanograms per milliliter (ng/mL)
Standard Deviation 9.78765
|
—
|
|
Plasma Paroxetine Concentrations at 12 Hours and 24 Hours After Administration of Study Drug at Week 8 or Withdrawal
paroxetine 30 mg, 12 hours, n=2
|
64.4285 nanograms per milliliter (ng/mL)
Standard Deviation 23.34372
|
—
|
|
Plasma Paroxetine Concentrations at 12 Hours and 24 Hours After Administration of Study Drug at Week 8 or Withdrawal
paroxetine 40 mg, 12 hours, n=3
|
108.9133 nanograms per milliliter (ng/mL)
Standard Deviation 9.01693
|
—
|
|
Plasma Paroxetine Concentrations at 12 Hours and 24 Hours After Administration of Study Drug at Week 8 or Withdrawal
paroxetine 40 mg, 24 hours, n=2
|
67.9855 nanograms per milliliter (ng/mL)
Standard Deviation 4.08778
|
—
|
Adverse Events
Placebo
Paroxetine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=27 participants at risk
Participants took placebo once daily in the treatment phase (8 weeks) and the taper phase (0 to 3 weeks).
|
Paroxetine
n=29 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
14.8%
4/27 • Serious adverse events (SAEs) and non-serious AEs were collected during the treatment (8 weeks at maximum) and taper phases (3 weeks at maximum). SAEs were also collected during the follow-up phase (2 weeks after the last dose of investigational product).
|
20.7%
6/29 • Serious adverse events (SAEs) and non-serious AEs were collected during the treatment (8 weeks at maximum) and taper phases (3 weeks at maximum). SAEs were also collected during the follow-up phase (2 weeks after the last dose of investigational product).
|
|
Infections and infestations
Influenza
|
7.4%
2/27 • Serious adverse events (SAEs) and non-serious AEs were collected during the treatment (8 weeks at maximum) and taper phases (3 weeks at maximum). SAEs were also collected during the follow-up phase (2 weeks after the last dose of investigational product).
|
3.4%
1/29 • Serious adverse events (SAEs) and non-serious AEs were collected during the treatment (8 weeks at maximum) and taper phases (3 weeks at maximum). SAEs were also collected during the follow-up phase (2 weeks after the last dose of investigational product).
|
|
Psychiatric disorders
Suicidal ideation
|
11.1%
3/27 • Serious adverse events (SAEs) and non-serious AEs were collected during the treatment (8 weeks at maximum) and taper phases (3 weeks at maximum). SAEs were also collected during the follow-up phase (2 weeks after the last dose of investigational product).
|
0.00%
0/29 • Serious adverse events (SAEs) and non-serious AEs were collected during the treatment (8 weeks at maximum) and taper phases (3 weeks at maximum). SAEs were also collected during the follow-up phase (2 weeks after the last dose of investigational product).
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
7.4%
2/27 • Serious adverse events (SAEs) and non-serious AEs were collected during the treatment (8 weeks at maximum) and taper phases (3 weeks at maximum). SAEs were also collected during the follow-up phase (2 weeks after the last dose of investigational product).
|
3.4%
1/29 • Serious adverse events (SAEs) and non-serious AEs were collected during the treatment (8 weeks at maximum) and taper phases (3 weeks at maximum). SAEs were also collected during the follow-up phase (2 weeks after the last dose of investigational product).
|
|
Nervous system disorders
Headache
|
0.00%
0/27 • Serious adverse events (SAEs) and non-serious AEs were collected during the treatment (8 weeks at maximum) and taper phases (3 weeks at maximum). SAEs were also collected during the follow-up phase (2 weeks after the last dose of investigational product).
|
6.9%
2/29 • Serious adverse events (SAEs) and non-serious AEs were collected during the treatment (8 weeks at maximum) and taper phases (3 weeks at maximum). SAEs were also collected during the follow-up phase (2 weeks after the last dose of investigational product).
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER