Caplyta versus placebo for adults with social anxiety disorder

Inclusion Criteria:

1. Male and female adults between 18 and 65 years of age (inclusive).
2. Written informed consent given prior to any study procedures.
3. Diagnosis of Social Anxiety Disorder (SAD) according to DSM-5 criteria, as determined by psychiatric evaluation with the Investigator and as confirmed by the MINI at Screening.
4. Minimum total score of 70 on the LSAS at Screening and Baseline visits.
5. Total Hamilton Depression Rating Scale (HAM-D) score of less than 16 at Screening and Baseline.
6. Clinical Global Impression of Severity (CGI-S) score of 4 or greater at Screening and Baseline.
7. All subjects of childbearing potential must commit to an effective form of contraception for the duration of the trial and for at least 4 weeks after it ends.

Effective forms of contraception include: condoms with spermicide, diaphragm with spermicide, hormonal contraceptive agents (oral, transdermal, or injectable), or implantable contraceptive devices.

Abstinence from heterosexual intercourse will also be considered an effective form of contraception, if abstinence is part of the subject's usual lifestyle.

Exclusion Criteria:

1. Subjects with a history of treatment refractory SAD, defined for this study as: a history of two or more failed treatment trials, with an FDA-approved SAD treatment, whereby a treatment trial is defined as a period of at least 6 weeks during which the subject received an adequate dosage of the SAD treatment. The minimum adequate dosage of FDA-approved SAD treatments is defined as follows:

   Paxil®/paroxetine: 20 mg Zoloft®/sertraline: 100 mg Effexor XR®/venlafaxine: 150 mg Luvox®/fluvoxamine: 100 mg
2. Subjects with any Axis I disorder other than SAD (e.g., post-traumatic stress disorder, obsessive compulsive disorder, panic disorder) within 24 weeks of the Baseline visit.

   Subjects with co-morbid MDD, GAD, dysthymia, ADHD, or specific phobias may be allowed if SAD is the primary disorder in terms of clinical severity, as determined by the investigator.
3. Subjects with any history or complication of schizophrenia or bipolar disorder.
4. Subjects with a complication of body dysmorphic disorder.
5. Subjects who are at risk of suicide, including:

   Subjects scoring \>2 on item #3 of the HAM-D at Screening or Baseline Subjects with recent (within the last 6 months prior to screening) suicidal behavior, defined as scoring "yes" on items 4 or 5 in the Suicidal Ideation section of the C-SSRS at Screening or Baseline Subjects who, in the opinion of the investigator, are at significant risk of suicide or suicidal behavior during the course of study participation Subjects with any suicide attempt within the 6 months prior to screening
6. Substance use disorder, as defined by DSM-5 criteria, within 24 weeks of Baseline.
7. Positive Urine Drug Screen at Baseline, unless due to prescribed medication.
8. Systolic blood pressure ≥165 and/or diastolic blood pressure ≥95, as measured at Screening and Baseline visits.
9. Current diagnosis of Diabetes Mellitus (type 1 or 2).
10. Current diagnosis or past history of significant cardiovascular disease.
11. Current hepatic impairment, including screening laboratory results showing:

    transaminases (ALT or AST) greater than 2 times the upper limit of normal (ULN), absolute neutrophil count (ANC) \< 1000, or active Hepatitis B or Hepatitis C.
12. Subjects with a history or complication of cancer or malignant tumor not in remission for at least 5 years. Basal cell skin cancers are not exclusionary.
13. Any history of seizure or seizure disorder, with the exception of a single childhood febrile seizure.
14. Any current unstable and/or clinically significant medical condition, based on history or as evidenced in screening laboratory results or ECG assessments.
15. Subjects with known hypersensitivity or allergy to lumateperone, or for whom Caplyta® is otherwise contraindicated.
16. Subjects receiving a moderate or strong CYP3A4 inhibitor, or any CYP3A4 inducer.
17. Subjects receiving fluoxetine within 28 days of Baseline.
18. Subjects receiving a MAO inhibitor within 14 days of the Baseline visit.
19. Subjects receiving any other psychotropics within 14 days of Baseline (including but not limited to: gabapentin, pregabalin, antipsychotics, SSRIs, SNRIs, benzodiazepines, and sedative hypnotics other than zolpidem).

    Zolpidem (Ambien®) PRN is allowed for insomnia, if not taken more than 3 times per week.

    Subjects on a stable dose of a beta-blocker for hypertension (stable for at least six months prior to Baseline) are not excluded from study participation.
20. Subjects who started psychotherapy or Cognitive Behavioral Therapy (CBT) within 24 weeks of Screening, except for supportive psychotherapy.

    Subjects who have been receiving psychotherapy or CBT for more than 24 weeks prior to Screening are eligible for the study, provided that the therapy continues at the same frequency for the duration of the trial.
21. Subjects who have received any electroconvulsive therapy (ECT) within 12 weeks of Baseline.
22. Subjects who are currently pregnant, lactating, or of childbearing potential and not able and willing to practice an effective method of contraception for the duration of the trial and at least 4 weeks after the final study visit.