Long Term Study of RBP 7000 in the Treatment of Subjects With Schizophrenia

An Open-Label, Long-Term Safety and Tolerability Study of RBP-7000 in the Treatment of Subjects With Schizophrenia

This is a Phase 3, open label study administering RBP-7000 in the treatment of patients with schizophrenia. Study will assess the long-term safety and tolerability of RBP-7000 subcutaneous (SC) injections in subjects with schizophrenia and to continue collecting clinical outcome data with RBP-7000 SC injections in subjects with schizophrenia using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Illness (CGI-S) scale.

Patients to be screened must be diagnosed with schizophrenia with a designated score based on the PANSS, as confirmed by a State, Assessability, Face, Ecological and Rule (SAFER) interview. "De novo" patients are patients who are already receiving 3- or 4-mg oral risperidone/day and will not have to complete the "run-in" or "conversion" phases (see below) and will be assigned to receive RBP-7000 after eligibility has been confirmed. Patients who completed the double-blind, placebo-controlled, efficacy study of RBP-7000 (RB-US-09-0010, NCT02109562), conducted in patients with acute schizophrenia (referred to as "roll-over" patients) will be screened.

All patients will be assigned the 120 mg dose of RBP-7000, which is subject to a one-time down-titration to 90-mg RBP-7000 for tolerability, at the investigator's discretion. Patients receiving the 90-mg dose of RBP-7000 who exhibit a worsening in psychiatric symptoms, confirmed by a total PANSS score >70 or a 20% increase in the PANSS score from the previous assessment at the 120-mg dose level (before the dose was decreased to 90 mg), can receive a one-time, up-titration back to 120-mg RBP-7000 at the discretion of the investigator.

"De novo" patients entering into the study are those patients who did not participate in study RB-US-09-0010 (NCT02109562) and are allocated into three groups with different pre-study procedures to prepare for the treatment period:

• "Run-in" patients are patients who are not already receiving oral risperidone (as no other antipsychotic medications are allowed during study participation) and will begin a 14-day run-in period by titrating up to a dose of 3 or 4 mg oral risperidone/day before the first injection of RBP-7000.
• "Conversion" patients are patients who are receiving oral risperidone doses other than 3 or 4mg/day and will begin a 7-day conversion period to achieve an oral risperidone dose level of 3 or 4-mg before the first injection of RBP-7000, only if clinically indicated.
• De novo patients taking an oral risperidone dose of 3 or 4 mg/day prestudy will (once screened/enrolled) receive the first injection of RBP-7000.

"Roll-over" patients entering into the study are patients who completed 56 days of double-blind treatment in Study RB-US-09-0010. These patients will be eligible to enter the current study provided that continuation of treatment is clinically warranted, as judged by the investigator, and that there have been no significant protocol deviations or clinically relevant adverse events (AEs) that would preclude inclusion in this study. Roll-over patients will not undergo the complete screening process and will not require either a run-in or conversion period with oral risperidone. On Day 1 of the open-label study (which is Day 57 of Study RB-US-09-0010), patients will receive their first injection (120 mg) of open label RBP-7000.

Inclusion Criteria:

"De Novo" Patients

• Diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual, Edition 4, text revision (DSM-IV-TR) criteria
• Total PANSS score <=70 at the time of screening (Visit 1)
• Otherwise healthy on the basis of physical examinatIon
• Provided written informed consent

"Roll-over Patients

• Provided written consent to participate in this study
• Be considered eligible to enroll based on End of Study (EOS) (Day 57 of Study RB-US-09-0010) assessments and the medical judgment of the investigator

Exclusion Criteria:

"De Novo" Patients

• Patients taking daily oral risperidone at a dose plus/minus 6 mg/day

• Patients taking any risperidone or 9-hydroxyrisperidone long-acting injectable formulation within 120 days of study screening (Visit 1)

• Patients who have received a long-acting injectable antipsychotic within 120 days of screening (Visit 1)

• Patients with evidence or history (in the past six months prior to screening) of a significant hepatic disorder that may either compromise patient safety or interfere with the safety and/or outcome evaluation of the study drug, including:

  • Acute or chronic hepatitis, including but not limited to hepatitis B or C
  • Total bilirubin greater than 1.5 times the upper limit of normal (ULN), or
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2 times ULN

• Patients with a history of drug-induced leukopenia

• Patients with other medical conditions including, but not limited to, history of heart attack (myocardial infarction) or brain injury (traumatic injury with loss of consciousness and/or cerebrovascular accident), and clinically significant low blood pressure or arrhythmias as interpreted by the primary investigator (PI) or medically qualified sub-investigator

• Patients with epilepsy or other seizure disorders, Parkinson's disease or dementia

"Roll-over" Patients

• Patients requiring an inpatient treatment setting at the end of Study RB-US-09-0010
• Patients with an unstable medical condition developed during Study RB-US-09-0010
• Women of childbearing potential who have a positive pregnancy test at screening (Visit 1), who are pregnant or breastfeeding, seeking pregnancy, or failing to use adequate contraceptive methods during the study