A Study in Pediatric Participants With Generalized Anxiety Disorder

Phase 3

Completed

Conditions: Anxiety Neuroses
Neuroses, Anxiety
Anxiety States, Neurotic

Interventions: Drug: Duloxetine
Drug: Placebo

Registration Number: NCT01226511

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this study is to find out if duloxetine \[30-120 milligrams (mg)\] given once a day by mouth for 10 weeks to children and adolescents, is better than placebo when treating Generalized Anxiety Disorder (GAD).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 281

Inclusion Criteria

Diagnosed with GAD on clinical exam as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and supported by the Mini International Neuropsychiatric Interview for children and adolescents (MINI-Kid)
Diagnosis of moderate or greater severity of GAD as determined by the following:
- Presence of 4 or more symptoms identified on the generalized anxiety subsection of the Pediatric Anxiety Rating Scale (PARS) symptom checklist at screening and randomization. Two of which are excessive worry and dread or fearful anticipation (nonspecific)
- PARS severity score of 15 or more at screening and randomization for symptoms identified on the generalized anxiety subsection of PARS symptom checklist at screening and randomization
- Clinical Global Impressions of Severity (CGI-S) rating of 4 or more at screening and randomization
- Presence of significant social, academic, and/or familial dysfunction as determined by the Children's Global Assessment Scale (CGAS) score of 60 or less at screening and randomization
Female participants must test negative for pregnancy during screening Furthermore, female participants must agree to abstain from sexual activity or to use a reliable method of birth control as determined by the investigator during the study
Participant's parent/legal representative and participant, if capable, are judged to be reliable by the investigator to keep all appointments for clinical visits, tests, and procedures required by the protocol
Participant's parent/legal representative and participant, if capable, must have a degree of understanding such that they can communicate intelligently with the investigator and study coordinator
Participants must be capable of swallowing study drug whole (without opening the capsule, crushing, dissolving, dividing, et cetera)
Participants must have venous access sufficient to allow blood sampling and are compliant with blood draws as per the protocol

Exclusion Criteria

Current diagnosis of major depressive disorder (MDD)
Participants for whom the primary focus of treatment is separation anxiety or social phobia (participants with secondary separation anxiety or social phobia are allowed to participate)
Have current primary diagnosis of any DSM-IV-TR Axis I disorder except GAD, or a current secondary DSM-IV-TR Axis 1 disorder that requires any pharmacologic treatment (other than those disorders listed below). Primary is defined as the disorder that is the primary focus of treatment
Have a history of DSM-IV-TR-defined substance abuse or dependence within the past year, excluding caffeine and nicotine
Have a current or previous diagnosis of bipolar disorder, psychotic depression, schizophrenia or other psychotic disorder, anorexia, bulimia, obsessive compulsive disorder, post-traumatic stress disorder, panic disorder, or pervasive development disorder, as judged by the investigator
Have 1 or more first-degree relatives (parents or siblings) with diagnosed bipolar I disorder
Have a serious or unstable medical illness, psychological condition, clinically significant laboratory or electrocardiogram (ECG) result, hypersensitivity to duloxetine, or its active ingredients, frequent or severe allergic reactions to multiple medications, uncontrolled narrow-angle glaucoma, acute liver injury (for example, hepatitis) or severe cirrhosis (Child-Pugh Class C), or a history of any seizure disorder (other than febrile seizures)
Have a significant suicide attempt within 1 year of screening or are currently at risk of suicide in the opinion of the investigator
Have initiated, stopped, or changed the type or intensity of psychotherapy within 6 weeks prior to screening. Participants who require a change to psychotherapy between weeks 1 through 10 will be excluded
Have a weight less than 20 kilograms at any time during the screening period
Female participants who are pregnant, nursing or have recently given birth

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Duloxetine	Duloxetine	30-120 mg flexible dosing once daily for 10 weeks. At the end of the 10 week blinded treatment period, participants may participate in an 18 week extension
Placebo	Duloxetine	Administered once daily for 10 weeks. At the end of the 10 week blinded treatment period, placebo participants receive duloxetine in the 18 week extension
Placebo	Placebo	Administered once daily for 10 weeks. At the end of the 10 week blinded treatment period, placebo participants receive duloxetine in the 18 week extension

Primary Outcome Measures

Name	Time	Method
Change From Baseline to 10-Week Endpoint in the Pediatric Anxiety Rating Scale (PARS) Severity Score Evaluated for Symptoms Identified on the Generalized Anxiety Subsection of the PARS Symptom Checklist	Baseline, 10 weeks	PARS severity score for GAD was assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist. PARS severity score for GAD was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 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. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for baseline, pooled investigator, age category, visit, treatment, treatment\visit, age category\visit, and baseline\*visit.

Secondary Outcome Measures

Name	Time	Method
Response Rate at Endpoint for Generalized Anxiety Disorder (GAD) Using Pediatric Anxiety Rating Scale (PARS) Severity Score for GAD	Baseline, 10 weeks	Response rate was defined as the percentage of participants having a 50% improvement from baseline to endpoint on the PARS severity score for GAD. PARS severity score for GAD was assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist. PARS severity score for GAD was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 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.
Change From Baseline to 10-Week Endpoint on the Pediatric Anxiety Rating Scale (PARS) Severity Total Score Evaluated for All Symptoms Identified on the PARS Symptom Checklist Symptoms	Baseline, 10 weeks	PARS severity total score was assessed for all symptoms identified on the PARS symptom checklist. PARS severity total score was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity total scores ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for treatment, pooled investigator, visit, baseline, age category, treatment\visit, baseline\visit, and age category\*visit.
Change From Baseline to 10-Week Endpoint on the Clinical Global Impression of Severity (CGI-S) Scale	Baseline, 10 weeks	The CGI-S scale evaluated the severity of illness at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicated a greater severity of illness. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for treatment, pooled investigator, visit, baseline, age category, treatment\visit, baseline\visit, and age category\*visit.
Remission Rate at Endpoint for Generalized Anxiety Disorder (GAD) Using Clinical Global Impressions of Severity (CGI-S) Scale	10 weeks	Remission rate was defined as the percentage of participants having a CGI-S score ≤2 at endpoint. The CGI-S scale evaluated the severity of illness at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicated a greater severity of illness.
Percentage of Participants During the 10-Week Period With Treatment-Emergent (New or Worsening) Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	Baseline up to 10 weeks	The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Results reported as percentage of participants with treatment-emergent (new or worsening) suicidal ideation from baseline=(number of participants with changes compared to baseline/total number of participants at risk)\*100.
Percentage of Participants During the 18-Week Extension Period With Treatment-Emergent (New or Worsening) Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	10 weeks up to 28 weeks	The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Reported as percentage of participants with treatment-emergent (new or worsening) suicidal behavior from baseline=(number of participants with changes compared to baseline/total number of participants at risk)\*100.
Change From Baseline to 10-Week Endpoint in the Children's Global Assessment Scale (CGAS)	Baseline, 10 weeks	The CGAS was a clinician-rated assessment of general functioning. CGAS raw scores ranged from 1 (greatest impairment) to 100 (superior functioning). Lower scores indicated a lower level of functioning and greater impairment. Least squares (LS) mean from an analysis of covariance (ANCOVA) was adjusted for treatment, pooled investigator, baseline, and age category.
Percentage of Participants During the 10-Week Period With Treatment-Emergent (New or Worsening) Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	Baseline up to 10 weeks	The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Reported as percentage of participants with treatment-emergent (new or worsening) suicidal behavior from baseline=(number of participants with changes compared to baseline/total number of participants at risk)\*100.
Change From 10-Week to 28-Week Endpoint in the Pediatric Anxiety Rating Scale (PARS) Severity Score Evaluated for Symptoms Identified on the Generalized Anxiety Subsection of the PARS Symptom Checklist	10 weeks, 28 weeks	PARS severity score for GAD was assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist. PARS severity score for GAD was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 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. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for pooled investigator, visit, baseline, age category, baseline\visit, and age category\visit within reporting groups.
Change From 10-Week to 28-Week Endpoint on the Pediatric Anxiety Rating Scale (PARS) Severity Total Score Evaluated for All Symptoms Identified on the PARS Symptom Checklist Symptoms	10 weeks, 28 weeks	PARS severity total score was assessed for all symptoms identified on the PARS symptom checklist. PARS severity total score was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity total scores ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for pooled investigator, visit, baseline, age category, baseline\visit, and age category\visit within reporting groups.
Change From 10-Week to 28-Week Endpoint on the Clinical Global Impression of Severity (CGI-S) Scale	10 weeks, 28 weeks	The CGI-S scale evaluated the severity of mental illness at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicated a greater severity of illness. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for pooled investigator, visit, baseline, age category, baseline\visit, and age category\visit within reporting groups.
Percentage of Participants During the 18-Week Extension Period With Treatment-Emergent (New or Worsening) Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	10 weeks up to 28 weeks	The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Results reported as percentage of participants with treatment-emergent (new or worsening) suicidal ideation from baseline=(number of participants with changes compared to baseline/total number of participants at risk)\*100.
Change From 10-Week to 28-Week Endpoint in the Children's Global Assessment Scale (CGAS)	10 weeks, 28 weeks	The CGAS was a clinician-rated assessment of general functioning. CGAS raw scores ranged from 1 (greatest impairment) to 100 (superior functioning). Lower scores indicated a lower level of functioning and greater impairment. Least squares (LS) mean from an analysis of covariance (ANCOVA) was adjusted for pooled investigator, baseline, and age category within reporting groups.

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇿🇦
Pretoria, South Africa