The Safety and Efficacy of Escitalopram in Pediatric Patients With Major Depressive Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Forest Laboratories
ClinicalTrials.gov Identifier:
NCT00107120
First received: April 5, 2005
Last updated: April 4, 2012
Last verified: April 2012
Results First Received: April 21, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Major Depressive Disorder
Interventions: Drug: Escitalopram
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment period was from April 1, 2005 through March, 2007 at 40 centers in the US.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
2 week screening with one-week single-blind placebo. Patients meeting selection criteria at baseline were randomized to once daily escitalopram 10-20mg/day or placebo (1:1).

Reporting Groups
  Description
Escitalopram Once daily oral administration of escitalopram tablets - 1 tablet (10mg) for the first three weeks, then 1 tablet (10mg or 20mg) depending on therapeutic response and tolerability.
Placebo Once daily oral administration of placebo tablets

Participant Flow:   Overall Study
    Escitalopram     Placebo  
STARTED     155 [1]   157 [1]
COMPLETED     126     133  
NOT COMPLETED     29     24  
Adverse Event                 4                 1  
Lack of Efficacy                 5                 5  
Protocol Violation                 3                 0  
Withdrawal by Subject                 8                 9  
Lost to Follow-up                 8                 6  
Pregnancy                 0                 1  
moving away from site                 1                 1  
death of parent                 0                 1  
[1] Safety Population defined as all patients who took at least one dose of double-blind study drug



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Escitalopram Once daily oral administration of escitalopram tablets - 1 tablet (10mg) for the first three weeks, then 1 tablet (10mg or 20mg) depending on therapeutic response and tolerability.
Placebo Once daily oral administration of placebo tablets
Total Total of all reporting groups

Baseline Measures
    Escitalopram     Placebo     Total  
Number of Participants  
[units: participants]
  155     157     312  
Age  
[units: participants]
     
<=18 years     155     157     312  
Between 18 and 65 years     0     0     0  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  14.7  ± 1.6     14.5  ± 1.5     14.6  ± 1.6  
Gender  
[units: participants]
     
Female     92     92     184  
Male     63     65     128  
Region of Enrollment  
[units: participants]
     
United States     155     157     312  



  Outcome Measures
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1.  Primary:   Change in Children's Depression Rating Scale - Revised (CDRS-R) Total Score   [ Time Frame: Baseline to end of week 8 ]

Measure Type Primary
Measure Title Change in Children's Depression Rating Scale - Revised (CDRS-R) Total Score
Measure Description Change from baseline to week 8 in Children's Depression Rating Scale total score. The scale measures 17 depressive symptoms, of which 3 are rated 1-5 and 14 are rated 1-7 (1 = no symptom difficulties; 5 or 7 = severe clinically significant difficulties) for a total score range of 17-113.
Time Frame Baseline to end of week 8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Efficacy analyses used Intent-To-Treat Population, which consisted of all patients who received at least 1 dose of double-blind study drug & who had at least 1 post-baseline assessment of the CDRS-R. LOCF technique was used to impute missing data. 1 escitalopram pt. did not have a post-baseline CDRS-R total score.

Reporting Groups
  Description
Escitalopram Once daily oral administration of escitalopram tablets - 1 tablet (10mg) for the first three weeks, then 1 tablet (10mg or 20mg) depending on therapeutic response and tolerability.
Placebo Once daily oral administration of placebo tablets

Measured Values
    Escitalopram     Placebo  
Number of Participants Analyzed  
[units: participants]
  154     157  
Change in Children's Depression Rating Scale - Revised (CDRS-R) Total Score  
[units: Change in total score at endpoint]
Mean ± Standard Error
  -22.4  ± 1.1     -18.4  ± 1.1  


Statistical Analysis 1 for Change in Children's Depression Rating Scale - Revised (CDRS-R) Total Score
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.022
Least Square Means Difference [4] -3.4
Standard Error of the mean ± 1.458
95% Confidence Interval ( -6.2 to -0.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The null hypothesis is that there is no difference in the Change from Baseline to Week 8 in CDRS-R total score between treatment groups. The power calculation was based on the change from baseline to Week 8 in CDRS-R total score (LOCF approach). Assuming an effect size (treatment group difference relative to standard deviation) of 0.325, a sample size of approximately 150 patients per treatment group was used to provide at least 80% power at a significance level of 0.05 using a two-sided test.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  The model included study center and treatment as factors and baseline core as covariate
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided at 5% level of significance p < 0.05 considered significant
[4] Other relevant estimation information:
  Differences are Escitalopram-Placebo



2.  Secondary:   Clinical Global Impressions - Improvement   [ Time Frame: CGI-I score at the end of Week 8 ]

Measure Type Secondary
Measure Title Clinical Global Impressions - Improvement
Measure Description Clinical Global Impressions - Improvement score at the end of week 8. The scale rates improvement or worsening of patient mental health relative to baseline on a scale from 1 (very much improved) to 7 (very much worse).
Time Frame CGI-I score at the end of Week 8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Intent-To-Treat Population was used. The Last Observation Carried Forward (LOCF) technique was used to impute missing data.

Reporting Groups
  Description
Escitalopram Once daily oral administration of escitalopram tablets - 1 tablet (10mg) for the first three weeks, then 1 tablet (10mg or 20mg) depending on therapeutic response and tolerability.
Placebo Once daily oral administration of placebo tablets

Measured Values
    Escitalopram     Placebo  
Number of Participants Analyzed  
[units: participants]
  154     157  
Clinical Global Impressions - Improvement  
[units: Score on scale]
Mean ± Standard Error
  2.2  ± 0.1     2.5  ± 0.1  


Statistical Analysis 1 for Clinical Global Impressions - Improvement
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.008
Least Square Means Difference [4] -0.344
Standard Error of the mean ± 0.1128
95% Confidence Interval ( -0.595 to 0.092 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Missing values were imputed using the LOCF approach.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  The model included treatment and center as factors and baseline CGI-Severity score as covariate.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided at 5% level of significance
[4] Other relevant estimation information:
  Differences are Escitalopram-Placebo



3.  Other Pre-specified:   Children's Global Assessment Scale   [ Time Frame: At baseline and end of week 8 ]

Measure Type Other Pre-specified
Measure Title Children's Global Assessment Scale
Measure Description Change from baseline to week 8 in CGAS score which rates the patient's general level of functioning for the past 14 days on a scale of 1 (most impaired) to 100 (healthiest).
Time Frame At baseline and end of week 8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Intent-To-Treat Population was used. The Last Observation Carried Forward (LOCF) technique was used to impute missing data.

Reporting Groups
  Description
Escitalopram Once daily oral administration of escitalopram tablets - 1 tablet (10mg) for the first three weeks, then 1 tablet (10mg or 20mg) depending on therapeutic response and tolerability.
Placebo Once daily oral administration of placebo tablets

Measured Values
    Escitalopram     Placebo  
Number of Participants Analyzed  
[units: participants]
  154     157  
Children's Global Assessment Scale  
[units: Change in score]
Mean ± Standard Error
  14.7  ± 1.0     12.4  ± 1.0  


Statistical Analysis 1 for Children's Global Assessment Scale
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.103
Least Square Means Difference [4] 2.169
Standard Error of the mean ± 1.324
95% Confidence Interval ( -0.439 to 4.777 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA on the Change from Baseline to Week 8 in CGAS score. The model included treatment and center as factors and baseline score as covariate. Missing values were imputed using the LOCF approach.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Two-sided at 5% level of significance
[4] Other relevant estimation information:
  Differences are Escitalopram-Placebo




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


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