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

The study will be conducted in 3 periods:

• Screening Period (up to 3 weeks) during which patient eligibility will be assessed and the washout of prohibited medications will occur.
• Double-blind Treatment Period (6 weeks) during which patients will be randomized in a 1:1:1 ratio to receive one of the 3 treatments (ITI-1284 10 mg, ITI-1284 20 mg, or placebo).
• Safety Follow-up Period (1 week) during which all patients will return for a safety follow-up visit.

Inclusion criteria

• Provide written informed consent before the initiation of any study specific procedures;
• Male or female patients ≥ 18 years of age;
• At Screening, meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) diagnostic criteria for moderate or severe 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:

• HAM-A Total score of ≥ 22;
• HAM-A Items 1 (anxious mood) and 2 (tension) scores ≥ 2;
• CGI-S score of ≥ 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 the minimum GAD-approved dose per package insert) and duration (ie, daily for at least 6 weeks) for the treatment of ongoing GAD symptoms;
• 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 the minimum GAD-approved dose per package insert) 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

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

• Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder;
• Bipolar Disorder;
• MADRS total score > 18 at Screening or Baseline;
• In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during his/her participation in the study or

• 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;
• At Screening, the patient has had 1 or more suicidal attempts within the 2 years prior to Screening;
• At Screening or Baseline MADRS Item 10 score ≥ 5; or
• The patient is considered to be an imminent danger to him/herself or others based on the assessment of the Investigator.
• 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 (ie, at least the minimum dose approved for GAD per package insert) and for an adequate duration (ie, at least 6 weeks).