Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy

NCT01677377 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RB-US-09-0009
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

Evaluate the safety and tolerability of multiple subcutaneous injections of various dosages of risperidone with clinically stable schizophrenia

Conditions

Schizophrenia

Keywords

Schizophrenia; Schizophrenic; Schizophrenias

Outcome Measures

Primary Outcomes (58)

• Summary of Participants With Treatment-Emergent Adverse Events (TEAE)

  An adverse event (AE) is defined as any study-related event that represents a change (positive or negative) in frequency or severity from a baseline (prestudy) event (if any), regardless of the presence of causal relationship or medical significance. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the first study dose date. AEs are determined by the Investigator to be related or not related to the study drug. A serious AE (SAE) is defined by federal regulation as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Although a subject may have had 2 or more adverse experiences the subject is counted only once in a category. The same subject may appear in different categories.

  Day 1 to Day 106

• Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] AUC0-24 calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-2, Day 57-58

• Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Cmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-2, Day 57-58

• Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Tmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-2, Day 57-58

• Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] AUCtau calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The average of plasma concentrations calculated as AUCtau/ tau (tau = 28 days) Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Total Risperidone PK: Percent Fluctuation Over the PK Profile

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Total Risperidone PK: Swing Over the PK Profile

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Accumulation index in terms of AUC calculated as ratio of AUCtau injection 3 / injection 1. Tau = 28 days. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Accumulation index in terms of Cmax calculated as ratio of Cmax injection 3 / injection 1. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Area under plasma concentration-time curve from 24 hours (Day 2) to the last quantifiable collection during dosing interval (28 days); calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 at time of study drug administration.

  Day 2-29, Day 58-85

• Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The average of plasma concentrations in the plateau, calculated as AUC Day 2-29/time Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: Secondary Peak, Injection 1 (Day 2 - Day 29) Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Total Risperidone PK: Percent Fluctuation Over the Secondary Peak

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Total Risperidone PK: Swing Over the Secondary Peak

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak

  Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)

  AUC0-24 calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-2, Day 57-58

• Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak

  Cmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-2, Day 57-58

• Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak

  Tmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-2, Day 57-58

• Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)

  AUCtau calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile

  The average of plasma concentrations calculated as AUCtau/ tau (tau = 28 days) Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile

  Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile

  Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Risperidone PK: Percent Fluctuation Over the PK Profile

  The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Risperidone PK: Swing Over the PK Profile

  The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile

  Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))

  Accumulation index in terms of AUC calculated as ratio of AUCtau injection 3 / injection 1. Tau = 28 days. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))

  Accumulation index in terms of Cmax calculated as ratio of Cmax injection 3 / injection 1. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)

  Area under plasma concentration-time curve from 24 hours (Day 2) to the last quantifiable collection during dosing interval (28 days); calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)

  The average of plasma concentrations in the plateau, calculated as AUC Day 2-29/time Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)

  Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: Secondary Peak, Injection 1 (Day 2 - Day 29) Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak

  Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Risperidone PK: Percent Fluctuation Over the Secondary Peak

  The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Risperidone PK: Swing Over the Secondary Peak

  The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak

  Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)

  AUC0-24 calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-2, Day 57-58

• 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak

  Cmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-2, Day 57-58

• 9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak

  Tmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-2, Day 57-58

• 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)

  AUCtau calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• 9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile

  The average of plasma concentrations calculated as AUCtau/ tau (tau = 28 days) Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile

  Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile

  Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• 9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile

  The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• 9-hydroxyrisperidone PK: Swing Over the PK Profile

  The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile

  Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))

  Accumulation index in terms of AUC calculated as ratio of AUCtau injection 3 / injection 1. Tau = 28 days. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))

  Accumulation index in terms of Cmax calculated as ratio of Cmax injection 3 / injection 1. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 1-28, Day 57-84

• 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)

  Area under plasma concentration-time curve from 24 hours (Day 2) to the last quantifiable collection during dosing interval (28 days); calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• 9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)

  The average of plasma concentrations in the plateau, calculated as AUC Day 2-29/time Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• 9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)

  Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: Secondary Peak, Injection 1 (Day 2 - Day 29) Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak

  Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• 9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak

  The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• 9-hydroxyrisperidone PK: Swing Over the Secondary Peak

  The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

• 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak

  Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration

  Day 2-29, Day 58-85

Secondary Outcomes (6)

• Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106

  Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)

• Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106

  Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)

• Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106

  Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)

• Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106

  Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)

• Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106

  Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)

Study Arms (3)

Cohort 1, RBP-7000 60 mg

EXPERIMENTAL

Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.

Drug: Risperidone; Drug: RBP-7000

Cohort 2, RBP-7000 90 mg

EXPERIMENTAL

Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.

Drug: Risperidone; Drug: RBP-7000

Cohort 3, RBP-7000 120 mg

EXPERIMENTAL

Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.

Drug: Risperidone; Drug: RBP-7000

Interventions

Risperidone DRUG

Oral risperidone was supplied as 2, 3, or 4 mg tablets in blister packs or bottles and taken daily only during the oral dosing periods of the study, days -14 through -8 (if applicable), days -7 through -1, and days 85 through 87.

Also known as: Risperdal

Cohort 1, RBP-7000 60 mg; Cohort 2, RBP-7000 90 mg; Cohort 3, RBP-7000 120 mg

RBP-7000 DRUG

RBP-7000 60 mg, 90 mg, and 120 mg were a mixture of the ATRIGEL® Delivery System and 60 mg, 90 mg, or 120 mg risperidone, respectively. Treatment was delivered as subcutaneous injections on study days 1, 29 and 57.

Also known as: risperidone in Atrigel

Cohort 1, RBP-7000 60 mg; Cohort 2, RBP-7000 90 mg; Cohort 3, RBP-7000 120 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female
• \> 18 to \< 65 years
• Diagnosis of paranoid, residual, or undifferentiated schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM-IV-TR) criteria
• Status: clinically stable subjects defined as subjects with no hospitalizations for acute exacerbations within 3 months of screening and screening total Positive and Negative Syndrome Scale (PANSS) score \< 60
• Subjects who have given written informed consent

You may not qualify if:

• Subjects taking any risperidone sustained release formulation within the 60 days prior to study screening
• Subjects taking the following concurrent medication/over-the-counter products:
• Inducers or inhibitors of cytochrome P450 2D6 (CYP-2D6) within 14 days or 7 half - lives (whichever occurs last) prior to study screening
• Bupropion, chlorpheniramine, cimetidine, clomipramine, doxepin, or quinidine within 30 days prior to study screening
• Clozapine, phenothiazines, aripiprazole, haloperidol, or any other antipsychotic other than oral risperidone within 14 days prior to study screening
• Selective serotonin reuptake inhibitors (e.g., fluoxetine, paroxetine) or serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine, desvenlafaxine, duloxetine) within 30 days prior to study screening
• Opioids or opioid-containing analgesics within 14 days prior to study screening
• Medications, in addition to those listed above, which may be expected to significantly interfere with the metabolism or excretion of risperidone and/or 9-hydroxyrisperidone, that may be associated with a significant drug interaction with risperidone, or that may pose a significant risk to subjects' participation in the study
• Subjects with a history of cancer (with the exception of resected basal cell or squamous cell carcinoma of the skin) unless they have been disease free for \>5 years
• Subjects with another active medical condition or organ disease that may either compromise subject safety and/or outcome evaluation of the study drug
• Subjects with evidence or history of a significant hepatic disorder that may either compromise subject safety or interfere with the safety and/or outcome evaluation of the study drug. Individuals with acute hepatitis (including but not limited to B or C); or individuals with 1) total bilirubin \>1.5x the upper limit of normal and/or 2) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2x upper limit of normal (ULN) will be excluded
• Subjects with hepatitis C antibody and AST, ALT, or alkaline phosphatase \>2x and total bilirubin \>1.3 mg/dL will be excluded
• Subjects with a history of renal disease, or a creatinine clearance of less than 80 mL/min (as determined by the Cockcroft Gault formula)
• Subjects with an international normalized ratio \>2.0 at screening
• Subjects with corrected QT interval (Bazett's - QTcB) \>450 msec (male) or \>470 msec (female) at screening. Subjects with a QTc above these levels due to a benign right bundle branch block can be included in the study at the discretion of the PI

Sponsors & Collaborators

• Indivior Inc.: lead

Study Sites (2)

Woodland International Research Group, Inc.

Little Rock, Alaska, 72211, United States

Location

Ocean View Psychiatric Health Facility

Long Beach, California, 90806, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Director, Clinical Development
• Organization: Indivior, Inc.

804-379-1090

Study Officials

• Philippa Whitelaw, Sr. Dir of Proj Deliver

  Pharmaceutical Research Associates

  STUDY DIRECTOR

• Ashley Huston, PMP

  Pharmaceutical Research Associates

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2012
• First Posted: September 3, 2012
• Study Start: August 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: October 23, 2018
• Results First Posted: October 23, 2018

Record last verified: 2018-10

Locations

US (2)