Study of ITI-1284 as an Adjunctive Treatment in Patients With Generalized Anxiety Disorder

A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of ITI-1284 as an Adjunctive Treatment in Patients With Generalized Anxiety Disorder Who Have an Inadequate Response to Generalized Anxiety Disorder Treatment

This is a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of ITI-1284 compared with placebo as adjunctive therapy to GAD treatment in patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) criteria for GAD who have an inadequate response to ongoing GAD treatment.

Inclusion Criteria:

1. Provide written informed consent before the initiation of any study specific procedures;

2. Male or female patients ≥ 18 years of age;

3. At Screening, meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) diagnostic criteria for moderate or severe GAD (current GAD) as confirmed by the Investigator or Sponsor-approved rater using the Structured Clinical Interview for DSM-5 Clinical Trials Version (SCID-5-CT), and meets all of the following at Screening and Baseline:

   1. HAM-A Total score of ≥ 22;
   2. HAM-A Items 1 (anxious mood) and 2 (tension) scores ≥ 2;
   3. CGI-S score of ≥ 4;

4. History of inadequate response (< 50% improvement in anxiety symptoms as measured by the modified Antidepressant Treatment Response Questionnaire [ATRQ] for GAD) to at least 1 GAD-approved treatment (ie, one of the following GAD-approved treatments: paroxetine, venlafaxine XR, duloxetine, escitalopram, or buspirone) taken at an adequate dose (at least a minimum total daily dose of paroxetine 20 milligrams [mg], venlafaxine XR 75 mg, duloxetine 60 mg, escitalopram 10 mg, or buspirone 20 mg) and duration (ie, daily for at least 6 weeks) for the treatment of ongoing GAD symptoms;

5. Currently having an inadequate response to one of the following GAD-approved treatments: paroxetine, venlafaxine XR, duloxetine, escitalopram, or buspirone taken at an adequate dose (at least a minimum total daily dose of paroxetine 20 mg, venlafaxine XR 75 mg, duloxetine 60 mg, escitalopram 10 mg, or buspirone 20 mg) and duration (ie, for at least 6 weeks prior to Screening) and agrees to continue the same dosing regimen for the duration of the study.

NOTE: The current GAD-approved treatment must be different from the GAD treatment identified as the historical failure.

Exclusion Criteria:

1. Within the patient's lifetime, has one of the following confirmed DSM-5-TR psychiatric diagnoses:

   1. Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder;
   2. Bipolar Disorder;

2. MADRS total score > 18 at Screening or Baseline;

3. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during his/her participation in the study or

   1. At Screening, the patient scores "yes" on Suicidal Ideation Items 4 or 5 of the C-SSRS within 6 months prior to Screening or, at Baseline, the patient scores "yes" on Suicidal Ideation Items 4 or 5 since the Screening Visit;
   2. At Screening, the patient has had 1 or more suicidal attempts within the 2 years prior to Screening;
   3. At Screening or Baseline MADRS Item 10 score ≥ 5; or
   4. The patient is considered to be an imminent danger to him/herself or others based on the assessment of the Investigator.

4. Lifetime history of failure to respond to > 3 of the approved treatments for GAD (ie, paroxetine, venlafaxine XR, duloxetine, escitalopram, or buspirone) at an adequate dose (at least a minimum total daily dose of paroxetine 20 mg, venlafaxine XR 75 mg, duloxetine 60 mg, escitalopram 10 mg, or buspirone 20 mg) and for an adequate duration (ie, at least 6 weeks).