Anxiety Disorders,Generalized Anxiety Disorder
Conditions
Brief summary
This is a study in minors (7 to 17 years old) diagnosed with generalized anxiety disorder (GAD) and evaluated using standard questionnaires as having at least moderate severity of GAD. Participating minors will be assigned to receive either the study drug escitalopram or a pill without any drug in it called a placebo. The purpose of this research is to study the safety and effectiveness of escitalopram in minors with GAD.
Interventions
DRUGEscitalopram
8-weeks of treatment followed by 1-week taper down period
OTHERPlacebo
Matching oral administration of inactive substance once daily
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subject's parent/legal representative must give written informed consent, including privacy authorization, prior to study participation. The subject will complete an informed assent prior to study participation. * Subject meets DSM-5 criteria for a primary diagnosis of GAD at screening established by a comprehensive psychiatric evaluation and confirmed/supported using the Mini-International Neuropsychiatric Interview for children and adolescents (MINI Kid). * Male subjects who are sexually active with a partner of childbearing potential must use, with their partner, a condom plus an approved method of highly effective contraception from the time of informed consent until 14 days after the last dose of study drug. * Female subjects who are sexually active and are of childbearing potential must use, with their partner, an approved method of highly effective contraception from the time of informed consent until 14 days after the last dose of study drug. * Female subjects who are not of childbearing potential do not need to use any methods of contraception. This includes preadolescent and adolescent females who have not reached menarche. - Subject must have venous access enough to allow blood sampling and be compliant with blood draws as per the protocol.
Exclusion criteria
* Current diagnosis of MDD, attention-deficit/hyperactivity disorder, or lifetime diagnosis of bipolar disorder, psychotic depression, schizophrenia or other psychotic disorder, feeding and/or eating disorder, obsessive-compulsive disorder, conduct disorder, oppositional defiant disorder, post-traumatic stress disorder, panic disorder, or pervasive development disorder. * Suspected or previously diagnosed intellectual disability disorder. * One or more first-degree relatives with diagnosed bipolar I disorder. * History of seizure disorder (other than febrile seizures). * History of electroconvulsive therapy at any time during the subject's lifetime. * Known hypersensitivity to escitalopram (escitalopram oxalate) or citalopram or any of the inactive ingredients or had frequent or severe allergic reactions to multiple medications. * Taking any medications that are contraindicated to escitalopram (escitalopram oxalate). * Inability to speak, read, or understand English well enough to complete the assessments. * No active suicidal ideation or lifetime history of suicidal behavior as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pediatric Anxiety Rating Scale (PARS) Severity Score | Baseline to Week 8 | The PARS is a clinician-rated instrument for assessing the severity of anxiety symptoms associated with common anxiety disorders including generalized anxiety disorder (GAD) in children. The PARS severity score for GAD will be assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist derived by summing 5 of the 7 severity/impairment/interference items (2, 3, 5, 6, and 7) each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity scores for GAD ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate on the PARS | Week 8 | Response is defined as a 50% improvement on the PARS severity score for GAD |
| Remission Rate on the PARS | Week 8 | Remission is defined as PARS severity score for GAD ≤8 (using 6 PARS items: 2, 3, 4, 5, 6, and 7) |
| Change on the Clinical Global Impression of Severity (CGI-S) | Week 8 | Remission rate on CGI-S at acute treatment endpoint (Week 8). Remission rate is defined as the percentage of subjects having a CGI-S score ≤2 at endpoint. CGI-S is a seven point scale where 1=Normal and 7=Among the most extremely ill patients. |
| Change on the Children's Global Assessment Scale (CGAS) | Week 8 | Remission rate on the CGAS at acute treatment endpoint (Week 8). Functional remission is defined as CGAS \>70. The CGAS used is a 100-point scale ranging from 1 to 100, with higher scores indicating better functioning. |
Countries
United States
Participant flow
Recruitment details
273 participants are included in the Safety Population with 136 participants being randomized to the Placebo group and 137 participants randomized to the Escitalopram group
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching oral administration of placebo once daily
Placebo: Matching oral administration of inactive substance once daily | 136 |
| Escitalopram 10 mg/Day Oral administration with the possibility of dose escalation to 20 mg/day at the investigator's discretion
Escitalopram: 8-weeks of treatment followed by 1-week taper down period | 137 |
| Total | 273 |
Baseline characteristics
| Characteristic | Placebo | Escitalopram 10 mg/Day | Total |
|---|---|---|---|
| Age, Continuous | 12.4 years STANDARD_DEVIATION 2.6 | 12.7 years STANDARD_DEVIATION 2.7 | 12.6 years STANDARD_DEVIATION 2.6 |
| Age, Customized 12 Years to 17 years | 91 Participants | 93 Participants | 184 Participants |
| Age, Customized 7 Years to 11 Years | 45 Participants | 44 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 31 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 114 Participants | 106 Participants | 220 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 13 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 110 Participants | 113 Participants | 223 Participants |
| Sex: Female, Male Female | 93 Participants | 94 Participants | 187 Participants |
| Sex: Female, Male Male | 43 Participants | 43 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 137 | 0 / 136 |
| other Total, other adverse events | 44 / 137 | 27 / 136 |
| serious Total, serious adverse events | 2 / 137 | 1 / 136 |
Outcome results
Primary
Change in Pediatric Anxiety Rating Scale (PARS) Severity Score
The PARS is a clinician-rated instrument for assessing the severity of anxiety symptoms associated with common anxiety disorders including generalized anxiety disorder (GAD) in children. The PARS severity score for GAD will be assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist derived by summing 5 of the 7 severity/impairment/interference items (2, 3, 5, 6, and 7) each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity scores for GAD ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity.
Time frame: Baseline to Week 8
Population: The modified Intent-to-treat (mITT) Population was defined as all subjects who were randomized and received at least 1 dose of study medication and had both baseline and at least 1 post-baseline primary efficacy measure (ie, PARS severity score).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Pediatric Anxiety Rating Scale (PARS) Severity Score | -6.38 score on a scale | Standard Error 0.494 |
| Escitalopram 10 mg/Day | Change in Pediatric Anxiety Rating Scale (PARS) Severity Score | -7.81 score on a scale | Standard Error 0.484 |
p-value: 0.028195% CI: [-2.69, -0.15]mixed-effects model for repeated measure
Secondary
Change on the Children's Global Assessment Scale (CGAS)
Remission rate on the CGAS at acute treatment endpoint (Week 8). Functional remission is defined as CGAS \>70. The CGAS used is a 100-point scale ranging from 1 to 100, with higher scores indicating better functioning.
Time frame: Week 8
Population: The modified Intent-to-treat (mITT) Population was defined as all subjects who were randomized and received at least 1 dose of study medication and had both baseline and at least 1 post-baseline primary efficacy measure (ie, PARS severity score).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change on the Children's Global Assessment Scale (CGAS) | 16.2 score on a scale | Standard Deviation 12.9 |
| Escitalopram 10 mg/Day | Change on the Children's Global Assessment Scale (CGAS) | 18.1 score on a scale | Standard Deviation 13.1 |
Secondary
Change on the Clinical Global Impression of Severity (CGI-S)
Remission rate on CGI-S at acute treatment endpoint (Week 8). Remission rate is defined as the percentage of subjects having a CGI-S score ≤2 at endpoint. CGI-S is a seven point scale where 1=Normal and 7=Among the most extremely ill patients.
Time frame: Week 8
Population: The modified Intent-to-treat (mITT) Population was defined as all subjects who were randomized and received at least 1 dose of study medication and had both baseline and at least 1 post-baseline primary efficacy measure (ie, PARS severity score).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change on the Clinical Global Impression of Severity (CGI-S) | -1.2 score on a scale | Standard Deviation 1.1 |
| Escitalopram 10 mg/Day | Change on the Clinical Global Impression of Severity (CGI-S) | -1.3 score on a scale | Standard Deviation 1 |
Secondary
Remission Rate on the PARS
Remission is defined as PARS severity score for GAD ≤8 (using 6 PARS items: 2, 3, 4, 5, 6, and 7)
Time frame: Week 8
Population: The modified Intent-to-treat (mITT) Population was defined as all subjects who were randomized and received at least 1 dose of study medication and had both baseline and at least 1 post-baseline primary efficacy measure (ie, PARS severity score).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Remission Rate on the PARS | 22 Participants |
| Escitalopram 10 mg/Day | Remission Rate on the PARS | 22 Participants |
p-value: 0.692895% CI: [0.56, 2.387]generalized linear mixed model (GLMMIX)
Secondary
Response Rate on the PARS
Response is defined as a 50% improvement on the PARS severity score for GAD
Time frame: Week 8
Population: The modified Intent-to-treat (mITT) Population was defined as all subjects who were randomized and received at least 1 dose of study medication and had both baseline and at least 1 post-baseline primary efficacy measure (ie, PARS severity score).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Response Rate on the PARS | 39 Participants |
| Escitalopram 10 mg/Day | Response Rate on the PARS | 49 Participants |
p-value: 0.452195% CI: [0.695, 2.258]generalized linear mixed model (GLMMIX)