Date

2021-06-29

Protocol

Protocol changed

Item Changed

Inclusion criteria

Previous Version

1.Age 18 years or older 2.Male or female not of childbearing potential unless using adequate contraception as determined by their Health Care Provider. 3.Meets current DSM-5 criteria for schizophrenia. Other psychiatric disorders may be present only as lifetime diagnoses if they are not relevant to the current episode of schizophrenia. 4.Has been diagnosed with schizophrenia within the past 10 years. 5.Has shown treatment-resistance according to psychiatric history, with the last failed treatment documented in the patient’s clinical records. 6.Has a Clinical Global Impression – Severity of disease (CGI-S) rating of moderately ill to severely ill (score of 4 to 6 [scale 1-7]). 7.Has a PANSS total score ? 70 at screening and baseline. 8.Has a score of 4 (moderate) or more on at least 2 of the following 4 PANSS symptoms of psychosis: P2 (Conceptual Disorganization), P3 (Hallucinatory Behavior), P6 (Suspiciousness/Persecution) and G9 (Unusual Thought Content); and a total score of at least 20 on the combined total of the PANSS symptom items: P1 (Delusions), P2 (Conceptual Disorganization), P3 (Hallucinatory Behavior), P4 (Excitement), P6 (Suspiciousness/Persecution), P7 (Hostility), and G9 (Unusual thought content). 9.Has a Global Assessment of Functioning (GAF) scale total score ? 50. 10.Is in need of anti-psychotic treatment and is currently receiving mono-therapy at a stable dose (minimally for 4 weeks prior to screening) at a minimal recommended therapeutic or higher dose of one antipsychotic (atypical or typical, other than clozapine). 11.Current level of schizophrenic symptoms has been present for at least one month, but not exceeding one year. 12.Patient is cooperative, able to take oral medication, able to understand the instructions and willing to complete all aspects of the study, and is capable of doing so. 13.Patient is residing with a caregiver at his/her home, or is either in a residential care facility or residing alone, with a caregiver available to help ensure compliance with dosing and scheduled office visits in either situation. 14.Patient has provided written informed consent prior to participating in the study. 15.Patient agrees to be hospitalized overnight if required for trial purposes or if the investigator deems it necessary to ensure the safety of the patient.

Next Version

The patient must meet all the following inclusion criteria to be eligible for enrollment into the study: Demographics 1. Age - 18 years, or older. 2. Sex – male, or female. For inclusion, female patients must be post-menopausal (age 50 or older with confirmed amenorrhea for >12 months), surgically sterilized, or protected with highly effective contraception, i.e. barrier method in combination with an oral hormonal contraceptive, or long-acting hormonal contraceptive alone (see guidelines in Appendix 5). Psychiatric 3. Meets current DSM-5 criteria for schizophrenia. Other psychiatric disorders may be present only as lifetime diagnoses if they are not relevant to the current episode of schizophrenia. [see Exclusion criteria below] 4. Has been diagnosed with schizophrenia within the past 15 years. 5. Has shown treatment-resistance according to psychiatric history, within the past 10 years, with the last failed treatment documented in the patient’s clinical records. “Treatment-resistant Schizophrenia” (TRS) is defined as a persistence of significant clinical symptoms despite adequate doses of two standard antipsychotic medications (other than clozapine) from two different chemical classes, including at least one atypical antipsychotic, for at least 6 weeks of treatment each. The last failed treatment trial must be documented. 6. Has a Clinical Global Impression – Severity of disease (CGI-S) rating of moderately ill to severely ill (score of 4 to 6 [scale 1-7]). 7. Has a PANSS total score ? 70 at screening and baseline. 8. Has a score of 4 (moderate) or more on at least 2 of the following 4 PANSS symptoms of psychosis: P2 (Conceptual Disorganization), P3 (Hallucinatory Behavior), P6 (Suspiciousness/Persecution) and G9 (Unusual Thought Content); and a total score of at least 20 on the combined total of the PANSS symptom items: P1 (Delusions), P2 (Conceptual Disorganization), P3 (Hallucinatory Behavior), P4 (Excitement), P6 (Suspiciousness/Persecution), P7 (Hostility), and G9 (Unusual thought content). 9. Has a Global Assessment of Functioning (GAF) scale total score ? 50. 10. Is in need of anti-psychotic treatment and is currently receiving mono-therapy at a stable dose (minimally for 4 weeks prior to screening) at a minimal recommended therapeutic or higher dose of one antipsychotic (atypical or typical, other than clozapine). Current use of quetiapine at a dose of 150 mg or less at night as a soporific will not be considered polypharmacy. 11. Current level of symptoms has been present for at least one month, but not exceeding one year. Procedural 12. Patient is cooperative, able to take oral medication, able to understand the instructions and willing to complete all aspects of the study, and is capable of doing so. 13. Patient is residing with a caregiver at his/her home, or is either in a residential care facility or residing alone, with a caregiver available to help ensure compliance with dosing and scheduled office visits in either situation. 14. Patient has provided written informed consent prior to participating in the study. 15. Patient agrees to be hospitalized overnight if required for trial purposes or if the investigator deems it necessary to ensure the safety of the patient.