Acute and Long-Term Antidepressant Treatment Success in Adolescents With Anxiety (AtLAS-A)

Study Overview
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Brief Summary
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Acute, double-blind, adaptively randomized treatment with duloxetine or escitalopram, followed by open-label naturalistic follow-up.

Detailed Description
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To identify predictors of the magnitude and trajectory of response to flexibly-dosed duloxetine and escitalopram response in adolescents with anxiety, including those with depressive symptoms. And also to examine long-term predictors of sustained response and relapse in adolescents. To examine predictors of developing depressive disorders in anxious adolescents.

Official Title
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Acute, Double-blind, Adaptively Randomized Treatment With Duloxetine or Escitalopram, Followed by Open-label Naturalistic Follow-up.

Conditions
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Anxiety, Depressive Symptoms

Intervention / Treatment
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* Drug: Duloxetine
* Drug: Escitalopram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written, informed assent and consent. Patients, parent/guardian/LAR must be fluent in the English. 12 to 17 years of age, inclusive, at Screening. Patients must meet DSM-512 criteria for generalized, social and/or separation anxiety disorder and/or panic disorder, confirmed by the MINI-KID. Caregiver who is willing to consent to be responsible for safety monitoring of the patient, provide information about the patient's condition, oversee the administration of the investigational product. No clinically significant abnormalities on physical examination. Negative pregnancy test at Screening in females. Negative urine drug screen at Screening. Sexually active patients must practice a reliable method of contraception (Section 15.0) that will continue for the duration of the study and for a minimum of 30 days following the end of study participation. Reliable methods of contraception are defined below; other forms of contraceptives (pharmacological and/or non-pharmacological) are not accepted: Surgical sterilization Oral contraceptives (e.g. estrogren-progestin combination or progestin) Transdermally-delivered contraceptives (e.g., Ortho-Evra), depot injections (e.g., Depo-Provera) Vaginal contraceptive ring (e.g., NuvaRing), contraceptive implants (e.g., Implanon, Norplant II/Jadelle) An intrauterine device Diaphragm plus condom. Exclusion Criteria: DSM-512 diagnosis other than generalized anxiety, social anxiety, separation anxiety or panic disorder(s) that is the primary focus of treatment. A history of intellectual disability. Suicide risk as determined by either: (1) any suicide attempt within the past 6 months and/or (2) significant risk at Visit 1 (Screening) or Visit 2 (Baseline), as judged by the Investigator. Allergy, intolerance, non-response or hypersensitivity to escitalopram or duloxetine. Subjects taking other medications that require a taper or washout of more than 5 days. Patients who have initiated/terminated psychotherapy/behavior therapy within 1 month before Visit 2 (Baseline), or who plan to initiate/change said therapies during the course of the study will be excluded; if the patient is engaged in psychotherapy, it must have been stable for 1 month prior to baseline. A clinically-significant medical illness. QTc >450 in males / >460 in females (prolonged QTc based on American Heart Association recommendations for Standardization and Interpretation of the EKG81 Alcohol or substance use disorder within the past 6 months (nicotine use is permitted). Positive urine pregnancy test/pregnancy or breast feeding. A positive urine drug screen. Patients who are unable to swallow capsules.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Duloxetine<br>Patients randomized to duloxetine, treatment will be initiated at 30 mg qAM through Week 4 (V5) (consistent with the registration trial for duloxetine in pediatric patients with generalized anxiety disorder). Then, duloxetine will be increased to 60 mg qAM at Week 4 (V5) and will be continued at this dose until Week 6 (V6) or the end of the acute phase of the study. Beginning at Week 6 (V6), duloxetine may be increased to 90 mg daily and at Week 8 (V7), may be increased to 120 mg daily. | Drug: Duloxetine<br>* Encapsulated duloxetine 30 mg, 60 mg; once-daily<br>* Other names: Irenka;|
| Active Comparator: Escitalopram<br>Patients randomized to escitalopram, will initiate treatment at 5 mg qAM for 1 week and then 10 mg qAM (the recommended starting dose for adolescents 12-17 years and the dose used in the pediatric registration trials). After Week 4 (V5), escitalopram will be increased to 15 mg and this dose will be continued until either Week 6 (V6) or the end of the acute phase of the study; however, at Week 6 (V6), escitalopram may be increased to 20 mg qAM based on efficacy. | Drug: Escitalopram<br>* Encapsulated escitalopram 5 mg, 10 mg, 15 mg, 20 mg; once-daily<br>* Other names: Lexapro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline 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 in children and adolescents. The PARS score is derived by summing 5 of the 7 severity/impairment/interference items (2, 3, 5, 6, and 7) | Baseline to Week 24 months (Early Term) | 
| Change from Baseline in the Clinical Global Impression of Severity (CGI-S) | CGI-S is a seven point scale where 1=Normal and 7=Among the most extremely ill patients. | Baseline to Week 10 (Early Term) |