Schizophrenia
Conditions
Keywords
Schizophrenia, Schizophrenic, Schizophrenias
Brief summary
Evaluate the safety and tolerability of multiple subcutaneous injections of various dosages of risperidone with clinically stable schizophrenia
Detailed description
This will be an open-label, Phase 2A, multiple ascending dose study in 1 to 3 sites, designed to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of multiple subcutaneous injections of 60mg, 90mg, and 120mg doses of risperidone in the RBP-7000 formulation, in subjects with clinically-stable schizophrenia who are on a once daily stable dose of 2mg, 3mg, or 4mg of oral risperidone.
Interventions
DRUGRisperidone
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.
DRUGRBP-7000
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.
Sponsors
Indivior Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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 * Subjects who are known to have AIDS or to be HIV positive * Subjects with suicidal ideation with intent and plan (Columbia-Suicide Severity Rating Scale (C-SSRS) affirmative answers to questions 4 and 5 of the ideation section) or suicide attempts within the last six months as noted on the C-SSRS, or subjects with uncontrolled depression in the opinion of the investigator * Subjects with known diagnosis of type 1 or 2 diabetes or subjects with Hemoglobin A1c \>7.0 at screening * Subjects who have participated in a clinical trial within 30 days prior to study screening * Subjects who meet the DSM-IV-TR criteria for alcohol abuse or dependence within the last six months of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Day 1 to Day 106 | 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. |
| Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Day 1-2, Day 57-58 | 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 |
| Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Day 1-2, Day 57-58 | 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 |
| Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Day 1-2, Day 57-58 | 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 |
| Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Day 1-28, Day 57-84 | 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 |
| Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Total Risperidone PK: Percent Fluctuation Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Total Risperidone PK: Swing Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | Day 1-28, Day 57-84 | 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 |
| Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | Day 1-28, Day 57-84 | 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 |
| Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Day 2-29, Day 58-85 | 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. |
| Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Day 2-29, Day 58-85 | 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 |
| Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Day 2-29, Day 58-85 | 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 |
| Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| Total Risperidone PK: Percent Fluctuation Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| Total Risperidone PK: Swing Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Day 1-2, Day 57-58 | 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 |
| Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Day 1-2, Day 57-58 | 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 |
| Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Day 1-2, Day 57-58 | 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 |
| Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Day 1-28, Day 57-84 | 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 |
| Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Risperidone PK: Percent Fluctuation Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Risperidone PK: Swing Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | Day 1-28, Day 57-84 | 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 |
| Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | Day 1-28, Day 57-84 | 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 |
| Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Day 2-29, Day 58-85 | 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 |
| Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Day 2-29, Day 58-85 | 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 |
| Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Day 2-29, Day 58-85 | 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 |
| Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| Risperidone PK: Percent Fluctuation Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| Risperidone PK: Swing Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Day 1-2, Day 57-58 | 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 |
| 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Day 1-2, Day 57-58 | 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 |
| 9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Day 1-2, Day 57-58 | 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 |
| 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Day 1-28, Day 57-84 | 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 |
| 9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| 9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| 9-hydroxyrisperidone PK: Swing Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Day 1-28, Day 57-84 | 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 |
| 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | Day 1-28, Day 57-84 | 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 |
| 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | Day 1-28, Day 57-84 | 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 |
| 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Day 2-29, Day 58-85 | 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 |
| 9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Day 2-29, Day 58-85 | 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 |
| 9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Day 2-29, Day 58-85 | 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 |
| 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| 9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| 9-hydroxyrisperidone PK: Swing Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
| 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Day 2-29, Day 58-85 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | The switch from oral risperidone to RBP-7000 subcutaneous injections for efficacy markers used the PANSS scores. The PANSS assessment is a medical scale designed to measure symptom severity among patients with schizophrenia. Each item is rated on a scale of 1=absent to 7=extreme. PANSS consists of three components: * The General Psychopathology Scale consists of 16 questions with a total range of 16 (no schizophrenia symptoms) to 112 (extreme schizophrenia symptoms). * Both the Positive Scale and the Negative Scale consists of 7 questions with a total range of 7 (no schizophrenia symptoms) to 49 (extreme symptoms) on each scale. The PANSS range for assuring stability was a total PANSS General Psychopathology Scale score of 70 or less, with no score of 4 on any of the 7 questions in the Positive scale. |
| 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) | The switch from oral risperidone to RBP-7000 subcutaneous injections for efficacy markers used CGI scores. The CGI is used in the assessment of global illness severity and change in clinical condition over time in psychiatric patients. Severity of illness is measured on a 7-point scale with 1=normal, not at all ill and 7=among the most extremely ill patients. Global improvement is measured on a 7-point scale with 1=very much improved, 4=no change and 7=very much worse as compared to the severity of illness at baseline. |
| 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) | The switch from oral risperidone to RBP-7000 subcutaneous injections for safety markers used AIMS. The AIMS is a scale that aids in the early detection and ongoing monitoring of tardive dyskinesia, a movement disorder that can result from long-term treatment with antipsychotic medication. By assessing the participant's body movement in specific positions requiring rotation, a psychiatrist is able to determine whether abnormal facial or body movements exist. The total score is the sum of 7 questions assessing movement plus 3 questions representing global assessments on the overall level of involuntary movement severity, incapacitation due to involuntary movement, and patient's awareness of involuntary movement. Each of the 10 questions are scored on a 0 (none) - 4 (extremely severe) scale. Plus two dental status questions are scored on a 0 (no) - 1 (yes) scale. The total score is therefore a scale of 0 (normal) - 42 (advanced tardive dyskinesia). |
| 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) | The switch from oral risperidone to RBP-7000 subcutaneous injections for safety markers used SAS. The SAS is a 10-item scale used to detect the presence of drug induced parkinsonism and extrapyramidal side effects, and evaluates symptom severity. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0 to 4 scale with 0=normal and 4=extreme description of the particular side effect. The total range is 0=no side effects observed to 40 = extreme of each of the 10 side effects. |
| 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) | The BAS is a scale that detects the presence and severity of any drug induced akathisia. The scale measures objective and subjective effects such as restlessness and awareness of restlessness, respectively. Participants are observed while seated, then while standing and engaged in neutral conversation. Symptoms observed during additional situations, such as participant behavior on the ward, may also be rated. Subjective phenomena should be elicited through direct questioning of the participant. The global clinical assessment is reported on a scale of 0 to 5, where 0 = absent and 5 = severe akathisia. |
| Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) 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) | The C-SSRS is a scale developed by the National Institute of Mental Health trial group as a counterpart to the FDA's categorization of suicidal events. It was developed by a careful review and consequent categorization of thoughts and behavior that were statistically identified as significantly related to suicidal behavior. The scale captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors throughout lifetime at screening, baseline, and for the time interval since last administration for repeat administrations during a study. This outcome reports the number of participants with suicidal ideation or behavior. |
Countries
United States
Participant flow
Pre-assignment details
This was an open-label, Phase 2A, multiple-ascending dose study performed at 2 sites in the U.S. Seventy subjects were screened and 45 subjects were enrolled and received RBP-7000.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1, RBP-7000 60 mg 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. | 15 |
| Cohort 2, RBP-7000 90 mg 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. | 15 |
| Cohort 3, RBP-7000 120 mg 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. | 15 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | Cohort 2, RBP-7000 90 mg | Total | Cohort 1, RBP-7000 60 mg | Cohort 3, RBP-7000 120 mg |
|---|---|---|---|---|
| Age, Continuous | 42.5 years STANDARD_DEVIATION 9.93 | 42.6 years STANDARD_DEVIATION 9.16 | 43.7 years STANDARD_DEVIATION 9.98 | 41.7 years STANDARD_DEVIATION 7.96 |
| Body Mass Index | 27.35 kg/m^2 STANDARD_DEVIATION 4.176 | 28.64 kg/m^2 STANDARD_DEVIATION 4.309 | 28.13 kg/m^2 STANDARD_DEVIATION 4.487 | 30.43 kg/m^2 STANDARD_DEVIATION 3.911 |
| Cytochrome P450 2D6 (CYP-2D6) Extensive | 14 Participants | 39 Participants | 11 Participants | 14 Participants |
| Cytochrome P450 2D6 (CYP-2D6) Intermediate | 0 Participants | 4 Participants | 3 Participants | 1 Participants |
| Cytochrome P450 2D6 (CYP-2D6) Poor | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 42 Participants | 14 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 175.50 cm STANDARD_DEVIATION 11.137 | 174.03 cm STANDARD_DEVIATION 9.372 | 172.19 cm STANDARD_DEVIATION 8.731 | 174.41 cm STANDARD_DEVIATION 8.346 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 28 Participants | 7 Participants | 10 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 15 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 7 Participants | 1 Participants |
| Sex: Female, Male Male | 11 Participants | 33 Participants | 8 Participants | 14 Participants |
| Weight | 84.07 kg STANDARD_DEVIATION 13.707 | 86.82 kg STANDARD_DEVIATION 14.98 | 83.76 kg STANDARD_DEVIATION 16.279 | 92.63 kg STANDARD_DEVIATION 14.075 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 11 / 15 | 11 / 15 | 8 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 1 / 15 |
Outcome results
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | 1.1 ratio |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | 1.5 ratio |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | 1.2 ratio |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | 0.997 ratio |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | 1.442 ratio |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | 1.076 ratio |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 1 | 4696.8 hr*ng/mL |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 3 | 5388.2 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 1 | 5222.9 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 3 | 8311.7 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 1 | 7891.0 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 3 | 11786.5 hr*ng/mL |
Primary
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
Time frame: Day 1-2, Day 57-58
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 1 | 237.0 hr*ng/mL |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 3 | 169.2 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 1 | 251.1 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 3 | 263.4 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 1 | 404.8 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 3 | 342.6 hr*ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 1 | 4927.0 hr*ng/mL |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 3 | 5538.3 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 1 | 5607.5 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 3 | 8546.7 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 1 | 9862.2 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 3 | 11666.9 hr*ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 1 | 7.332 ng/mL |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 3 | 8.242 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 1 | 8.344 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 3 | 12.718 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 3 | 17.361 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 1 | 14.676 ng/mL |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 1 | 7.248 ng/mL |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 3 | 8.315 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 1 | 8.060 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 3 | 12.827 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 1 | 12.177 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 3 | 18.189 ng/mL |
Primary
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
Time frame: Day 1-2, Day 57-58
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 1 | 11.100 ng/mL |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 3 | 9.470 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 1 | 12.900 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 3 | 12.900 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 1 | 17.500 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 3 | 17.450 ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 1 | 12.300 ng/mL |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 3 | 13.450 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 1 | 15.600 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 3 | 21.200 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 1 | 22.400 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 3 | 29.600 ng/mL |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 1 | 12.300 ng/mL |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 3 | 13.450 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 1 | 15.600 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 3 | 21.200 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 1 | 22.300 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 3 | 29.600 ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 1 | 3.940 ng/mL |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 3 | 4.180 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 1 | 4.240 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 3 | 6.580 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 1 | 6.690 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 3 | 8.365 ng/mL |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 1 | 3.940 ng/mL |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 3 | 4.180 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 1 | 4.250 ng/mL |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 3 | 7.660 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 1 | 7.060 ng/mL |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 3 | 11.450 ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 1 | 120.024 percentage of average concentration |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 3 | 121.077 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 1 | 124.696 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 3 | 106.728 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 1 | 142.828 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 3 | 122.701 percentage of average concentration |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 1 | 112.945 percentage of average concentration |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 3 | 106.055 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 1 | 127.274 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 3 | 104.207 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 1 | 141.300 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 3 | 101.956 percentage of average concentration |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Swing Over the PK Profile | Overall, Injection 1 | 1.984 ratio |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Swing Over the PK Profile | Overall, Injection 3 | 2.901 ratio |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Swing Over the PK Profile | Overall, Injection 1 | 2.041 ratio |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Swing Over the PK Profile | Overall, Injection 3 | 2.142 ratio |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Swing Over the PK Profile | Overall, Injection 1 | 2.633 ratio |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Swing Over the PK Profile | Overall, Injection 3 | 2.240 ratio |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 3 | 2.018 ratio |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 1 | 1.936 ratio |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 3 | 1.991 ratio |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 1 | 2.041 ratio |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 1 | 2.633 ratio |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 3 | 1.595 ratio |
Primary
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
Time frame: Day 1-2, Day 57-58
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 1 | 4.000 hours |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 3 | 24.000 hours |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 1 | 6.000 hours |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 3 | 24.000 hours |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 1 | 6.000 hours |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 3 | 24.000 hours |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 1 | 168.000 hours |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 3 | 216.000 hours |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 1 | 168.000 hours |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 3 | 264.000 hours |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 3 | 216.000 hours |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 1 | 192.000 hours |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 1 | 216.000 hours |
| Cohort 1, RBP-7000 60 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 3 | 228.000 hours |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 1 | 168.000 hours |
| Cohort 2, RBP-7000 90 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 3 | 264.000 hours |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 3 | 216.000 hours |
| Cohort 3, RBP-7000 120 mg | 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 1 | 216.000 hours |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | 1.1 ratio |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | 1.7 ratio |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | 1.1 ratio |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | 1.049 ratio |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | 1.214 ratio |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | 1.155 ratio |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 1 | 1198.2 hr*ng/mL |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 3 | 2204.6 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 1 | 1544.9 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 3 | 2494.8 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 1 | 2937.3 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 3 | 3476.6 hr*ng/mL |
Primary
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
Time frame: Day 1-2, Day 57-58
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 1 | 103.8 hr*ng/mL |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 3 | 98.7 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 1 | 87.8 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 3 | 107.1 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 1 | 99.5 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 3 | 127.0 hr*ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 3 | 2144.6 hr*ng/mL |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 1 | 1250.9 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 1 | 1663.4 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 3 | 2647.1 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 1 | 3099.4 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 3 | 3621.2 hr*ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 1 | 1.861 ng/mL |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 3 | 3.191 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 1 | 2.475 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 3 | 3.939 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 1 | 4.612 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 3 | 5.389 ng/mL |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 1 | 1.849 ng/mL |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 3 | 3.402 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 1 | 2.384 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 3 | 3.850 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 1 | 4.533 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 3 | 5.365 ng/mL |
Primary
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
Time frame: Day 1-2, Day 57-58
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 3 | 4.955 ng/mL |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 1 | 6.280 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 1 | 5.460 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 3 | 6.680 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 1 | 6.470 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 3 | 7.145 ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 1 | 6.280 ng/mL |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 3 | 5.720 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 1 | 7.520 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 3 | 7.490 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 1 | 9.270 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 3 | 12.125 ng/mL |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 1 | 3.120 ng/mL |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 3 | 5.220 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 1 | 5.950 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 3 | 7.010 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 1 | 7.950 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 3 | 12.125 ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 1 | 0.829 ng/mL |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 3 | 1.230 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 1 | 1.060 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 3 | 2.100 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 1 | 1.720 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 3 | 2.415 ng/mL |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 1 | 0.829 ng/mL |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 3 | 1.230 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 1 | 1.070 ng/mL |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 3 | 2.100 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 1 | 1.720 ng/mL |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 3 | 2.415 ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 1 | 190.745 percentage of average concentration |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 3 | 147.252 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 1 | 215.048 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 3 | 140.688 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 1 | 173.609 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 3 | 143.652 percentage of average concentration |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 1 | 134.805 percentage of average concentration |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 3 | 136.691 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 1 | 134.898 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 3 | 125.387 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 1 | 141.030 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 3 | 138.380 percentage of average concentration |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Swing Over the PK Profile | Overall, Injection 1 | 4.575 ratio |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Swing Over the PK Profile | Overall, Injection 3 | 4.077 ratio |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Swing Over the PK Profile | Overall, Injection 1 | 4.151 ratio |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Swing Over the PK Profile | Overall, Injection 3 | 2.863 ratio |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Swing Over the PK Profile | Overall, Injection 1 | 4.938 ratio |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Swing Over the PK Profile | Overall, Injection 3 | 3.159 ratio |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 3 | 3.736 ratio |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 1 | 2.644 ratio |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 1 | 2.680 ratio |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 3 | 2.652 ratio |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 1 | 3.813 ratio |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 3 | 2.698 ratio |
Primary
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
Time frame: Day 1-2, Day 57-58
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 1 | 6.000 hours |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 3 | 6.000 hours |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 3 | 6.000 hours |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 1 | 6.000 hours |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 3 | 4.483 hours |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 1 | 4.000 hours |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 1 | 6.000 hours |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 3 | 18.000 hours |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 1 | 168.000 hours |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 3 | 192.000 hours |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 1 | 192.000 hours |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 3 | 180.000 hours |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 1 | 120.000 hours |
| Cohort 1, RBP-7000 60 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 3 | 204.000 hours |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 1 | 216.000 hours |
| Cohort 2, RBP-7000 90 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 3 | 216.00 hours |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 1 | 192.000 hours |
| Cohort 3, RBP-7000 120 mg | Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 3 | 180.000 hours |
Primary
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.
Time frame: Day 1 to Day 106
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | 1 or more TEAEs | 11 Participants |
| Cohort 1, RBP-7000 60 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Serious, related TEAE | 0 Participants |
| Cohort 1, RBP-7000 60 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Serious TEAEs | 0 Participants |
| Cohort 1, RBP-7000 60 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | No TEAEs | 4 Participants |
| Cohort 1, RBP-7000 60 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Death | 0 Participants |
| Cohort 1, RBP-7000 60 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE causing discontinuation | 0 Participants |
| Cohort 1, RBP-7000 60 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Related TEAEs | 6 Participants |
| Cohort 2, RBP-7000 90 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Serious TEAEs | 0 Participants |
| Cohort 2, RBP-7000 90 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | No TEAEs | 4 Participants |
| Cohort 2, RBP-7000 90 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | 1 or more TEAEs | 11 Participants |
| Cohort 2, RBP-7000 90 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Related TEAEs | 11 Participants |
| Cohort 2, RBP-7000 90 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Serious, related TEAE | 0 Participants |
| Cohort 2, RBP-7000 90 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE causing discontinuation | 0 Participants |
| Cohort 2, RBP-7000 90 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Death | 0 Participants |
| Cohort 3, RBP-7000 120 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Serious, related TEAE | 0 Participants |
| Cohort 3, RBP-7000 120 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | 1 or more TEAEs | 8 Participants |
| Cohort 3, RBP-7000 120 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Death | 0 Participants |
| Cohort 3, RBP-7000 120 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE causing discontinuation | 0 Participants |
| Cohort 3, RBP-7000 120 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Serious TEAEs | 1 Participants |
| Cohort 3, RBP-7000 120 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | Related TEAEs | 4 Participants |
| Cohort 3, RBP-7000 120 mg | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | No TEAEs | 7 Participants |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | 1.1 ratio |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | 1.6 ratio |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) | 1.2 ratio |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | 0.976 ratio |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | 1.525 ratio |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) | 1.105 ratio |
Primary
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.
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 1 | 6186.9 hr*ng/mL |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 3 | 8236.4 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 1 | 7735.1 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 3 | 10988.6 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 1 | 10001.4 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) | Secondary Peak, Injection 3 | 15484.3 hr*ng/mL |
Primary
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
Time frame: Day 1-2, Day 57-58
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 1 | 335.4 hr*ng/mL |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 3 | 276.5 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 1 | 437.5 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 3 | 415.1 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 1 | 466.2 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) | Initial Peak, Injection 3 | 497.5 hr*ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 1 | 6506.0 hr*ng/mL |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 3 | 8567.1 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 1 | 8293.8 hr*ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 3 | 11047.7 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 1 | 12594.7 hr*ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) | Overall, Injection 3 | 15982.6 hr*ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 1 | 9.682 ng/mL |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 3 | 12.749 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 1 | 12.342 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 3 | 16.440 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 1 | 18.742 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile | Overall, Injection 3 | 23.784 ng/mL |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 1 | 9.548 ng/mL |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 3 | 12.710 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 1 | 11.937 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 3 | 16.958 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 1 | 15.434 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) | Secondary Peak, Injection 3 | 23.896 ng/mL |
Primary
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
Time frame: Day 1-2, Day 57-58
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 1 | 16.343 ng/mL |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 3 | 14.549 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 1 | 19.415 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 3 | 16.973 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 1 | 24.400 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak | Initial Peak, Injection 3 | 22.852 ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 1 | 16.878 ng/mL |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 3 | 17.885 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 1 | 22.825 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 3 | 30.804 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 1 | 32.235 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile | Overall, Injection 3 | 38.300 ng/mL |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 1 | 16.867 ng/mL |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 3 | 17.885 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 1 | 21.415 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 3 | 30.804 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 1 | 32.235 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) | Secondary Peak, Injection 3 | 38.300 ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 1 | 4.867 ng/mL |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 3 | 5.028 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 1 | 5.642 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 3 | 10.534 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 1 | 9.159 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile | Overall, Injection 3 | 11.938 ng/mL |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 1 | 4.867 ng/mL |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 3 | 5.028 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 1 | 5.642 ng/mL |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 3 | 10.534 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 1 | 9.159 ng/mL |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak | Secondary Peak, Injection 3 | 13.735 ng/mL |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 1 | 151.211 percentage of average concentration |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 3 | 108.226 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 1 | 135.238 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 3 | 102.396 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 1 | 153.386 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Percent Fluctuation Over the PK Profile | Overall, Injection 3 | 114.008 percentage of average concentration |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 1 | 122.350 percentage of average concentration |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 3 | 101.788 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 1 | 122.042 percentage of average concentration |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 3 | 101.666 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 1 | 151.294 percentage of average concentration |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Percent Fluctuation Over the Secondary Peak | Secondary Peak, Injection 3 | 96.489 percentage of average concentration |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Swing Over the PK Profile | Overall, Injection 1 | 2.502 ratio |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Swing Over the PK Profile | Overall, Injection 3 | 2.588 ratio |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Swing Over the PK Profile | Overall, Injection 1 | 2.150 ratio |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Swing Over the PK Profile | Overall, Injection 3 | 2.052 ratio |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Swing Over the PK Profile | Overall, Injection 1 | 2.928 ratio |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Swing Over the PK Profile | Overall, Injection 3 | 2.019 ratio |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 1 | 2.048 ratio |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 3 | 2.412 ratio |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 1 | 2.017 ratio |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 3 | 1.914 ratio |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 1 | 2.928 ratio |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Swing Over the Secondary Peak | Secondary Peak, Injection 3 | 1.679 ratio |
Primary
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
Time frame: Day 1-2, Day 57-58
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 1 | 6.000 hours |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 3 | 17.917 hours |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 1 | 6.000 hours |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 3 | 24.000 hours |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 1 | 6.000 hours |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak | Initial Peak, Injection 3 | 24.000 hours |
Primary
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
Time frame: Day 1-28, Day 57-84
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 1 | 168.000 hours |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 3 | 216.00 hours |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 3 | 264.067 hours |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 1 | 215.833 hours |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 1 | 192.000 hours |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile | Overall, Injection 3 | 216.000 hours |
Primary
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
Time frame: Day 2-29, Day 58-85
Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 1 | 168.000 hours |
| Cohort 1, RBP-7000 60 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 3 | 228.000 hours |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 1 | 264.000 hours |
| Cohort 2, RBP-7000 90 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 3 | 264.067 hours |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 1 | 192.000 hours |
| Cohort 3, RBP-7000 120 mg | Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak | Secondary Peak, Injection 3 | 216.000 hours |
Secondary
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
The switch from oral risperidone to RBP-7000 subcutaneous injections for efficacy markers used CGI scores. The CGI is used in the assessment of global illness severity and change in clinical condition over time in psychiatric patients. Severity of illness is measured on a 7-point scale with 1=normal, not at all ill and 7=among the most extremely ill patients. Global improvement is measured on a 7-point scale with 1=very much improved, 4=no change and 7=very much worse as compared to the severity of illness at baseline.
Time frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
Population: Safety
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 84: Global improvement | 4.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Baseline: Severity of illness | 3.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 56: Severity of illness | 3.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 28: Global improvement | 4.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 28: Severity of illness | 3.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 56: Global improvement | 4.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 106: Global improvement | 4.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 84: Severity of illness | 3.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 106: Severity of illness | 3.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 84: Severity of illness | 3.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 84: Global improvement | 4.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Baseline: Severity of illness | 3.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 106: Severity of illness | 3.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 106: Global improvement | 4.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 28: Global improvement | 4.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 56: Severity of illness | 3.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 56: Global improvement | 4.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 28: Severity of illness | 3.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 56: Severity of illness | 3.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 106: Global improvement | 4.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Baseline: Severity of illness | 3.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 28: Severity of illness | 3.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 28: Global improvement | 4.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 56: Global improvement | 4.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 84: Severity of illness | 3.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 84: Global improvement | 4.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 | Day 106: Severity of illness | 3.0 units on a scale |
Secondary
Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106
The switch from oral risperidone to RBP-7000 subcutaneous injections for safety markers used AIMS. The AIMS is a scale that aids in the early detection and ongoing monitoring of tardive dyskinesia, a movement disorder that can result from long-term treatment with antipsychotic medication. By assessing the participant's body movement in specific positions requiring rotation, a psychiatrist is able to determine whether abnormal facial or body movements exist. The total score is the sum of 7 questions assessing movement plus 3 questions representing global assessments on the overall level of involuntary movement severity, incapacitation due to involuntary movement, and patient's awareness of involuntary movement. Each of the 10 questions are scored on a 0 (none) - 4 (extremely severe) scale. Plus two dental status questions are scored on a 0 (no) - 1 (yes) scale. The total score is therefore a scale of 0 (normal) - 42 (advanced tardive dyskinesia).
Time frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
Population: Safety
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 84 | 0.5 units on a scale |
| Cohort 1, RBP-7000 60 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 56 | 1.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Baseline | 1.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 28 | 1.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 106 | 1.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 56 | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Baseline | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 28 | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 84 | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 106 | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 106 | 0.5 units on a scale |
| Cohort 3, RBP-7000 120 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 84 | 1.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Baseline | 1.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 56 | 1.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 | Day 28 | 1.0 units on a scale |
Secondary
Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106
The BAS is a scale that detects the presence and severity of any drug induced akathisia. The scale measures objective and subjective effects such as restlessness and awareness of restlessness, respectively. Participants are observed while seated, then while standing and engaged in neutral conversation. Symptoms observed during additional situations, such as participant behavior on the ward, may also be rated. Subjective phenomena should be elicited through direct questioning of the participant. The global clinical assessment is reported on a scale of 0 to 5, where 0 = absent and 5 = severe akathisia.
Time frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
Population: Safety
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 84 | 0.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 56 | 0.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Baseline | 0.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 28 | 0.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 106 | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 56 | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Baseline | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 28 | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 84 | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 106 | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 106 | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 84 | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Baseline | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 56 | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 | Day 28 | 0.0 units on a scale |
Secondary
Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106
The C-SSRS is a scale developed by the National Institute of Mental Health trial group as a counterpart to the FDA's categorization of suicidal events. It was developed by a careful review and consequent categorization of thoughts and behavior that were statistically identified as significantly related to suicidal behavior. The scale captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors throughout lifetime at screening, baseline, and for the time interval since last administration for repeat administrations during a study. This outcome reports the number of participants with suicidal ideation or behavior.
Time frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
Population: Safety
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Baseline: Suicidal ideation or behavior | 0 Participants |
| Cohort 1, RBP-7000 60 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 106: Suicidal ideation or behavior | 0 Participants |
| Cohort 1, RBP-7000 60 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 28: Suicidal ideation or behavior | 0 Participants |
| Cohort 1, RBP-7000 60 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 84: Suicidal ideation or behavior | 0 Participants |
| Cohort 1, RBP-7000 60 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 56: Suicidal ideation or behavior | 1 Participants |
| Cohort 2, RBP-7000 90 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 56: Suicidal ideation or behavior | 0 Participants |
| Cohort 2, RBP-7000 90 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 84: Suicidal ideation or behavior | 0 Participants |
| Cohort 2, RBP-7000 90 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 106: Suicidal ideation or behavior | 0 Participants |
| Cohort 2, RBP-7000 90 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 28: Suicidal ideation or behavior | 1 Participants |
| Cohort 2, RBP-7000 90 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Baseline: Suicidal ideation or behavior | 0 Participants |
| Cohort 3, RBP-7000 120 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 56: Suicidal ideation or behavior | 0 Participants |
| Cohort 3, RBP-7000 120 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Baseline: Suicidal ideation or behavior | 0 Participants |
| Cohort 3, RBP-7000 120 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 28: Suicidal ideation or behavior | 1 Participants |
| Cohort 3, RBP-7000 120 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 106: Suicidal ideation or behavior | 0 Participants |
| Cohort 3, RBP-7000 120 mg | Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 | Day 84: Suicidal ideation or behavior | 0 Participants |
Secondary
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
The switch from oral risperidone to RBP-7000 subcutaneous injections for efficacy markers used the PANSS scores. The PANSS assessment is a medical scale designed to measure symptom severity among patients with schizophrenia. Each item is rated on a scale of 1=absent to 7=extreme. PANSS consists of three components: * The General Psychopathology Scale consists of 16 questions with a total range of 16 (no schizophrenia symptoms) to 112 (extreme schizophrenia symptoms). * Both the Positive Scale and the Negative Scale consists of 7 questions with a total range of 7 (no schizophrenia symptoms) to 49 (extreme symptoms) on each scale. The PANSS range for assuring stability was a total PANSS General Psychopathology Scale score of 70 or less, with no score of 4 on any of the 7 questions in the Positive scale.
Time frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
Population: Safety
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 28: Negative Scale | 16.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Baseline: Negative Scale | 15.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 84: Positive Scale | 13.5 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 56: General Psychopathology Scale | 28.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Baseline: Positive Scale | 13.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 84: General Psychopathology Scale | 28.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 56: Positive Scale | 13.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 106: General Psychopathology Scale | 26.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 56: Negative Scale | 17.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 28: General Psychopathology Scale | 28.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 106: Negative Scale | 14.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Baseline: General Psychopathology Scale | 27.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 28: Positive Scale | 13.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 106: Positive Scale | 13.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 84: Negative Scale | 15.5 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 84: Negative Scale | 17.5 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Baseline: General Psychopathology Scale | 24.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Baseline: Positive Scale | 14.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Baseline: Negative Scale | 18.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 28: General Psychopathology Scale | 26.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 28: Positive Scale | 12.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 28: Negative Scale | 17.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 56: General Psychopathology Scale | 26.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 56: Positive Scale | 13.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 56: Negative Scale | 18.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 84: General Psychopathology Scale | 25.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 84: Positive Scale | 12.5 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 106: General Psychopathology Scale | 23.5 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 106: Positive Scale | 12.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 106: Negative Scale | 18.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 28: Negative Scale | 18.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 106: Positive Scale | 14.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 84: Positive Scale | 12.5 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 28: Positive Scale | 12.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 28: General Psychopathology Scale | 27.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 84: Negative Scale | 16.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Baseline: Negative Scale | 18.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Baseline: General Psychopathology Scale | 27.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 106: General Psychopathology Scale | 26.5 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 56: Positive Scale | 11.5 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Baseline: Positive Scale | 13.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 56: Negative Scale | 17.5 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 56: General Psychopathology Scale | 25.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 106: Negative Scale | 18.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 | Day 84: General Psychopathology Scale | 25.0 units on a scale |
Secondary
Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106
The switch from oral risperidone to RBP-7000 subcutaneous injections for safety markers used SAS. The SAS is a 10-item scale used to detect the presence of drug induced parkinsonism and extrapyramidal side effects, and evaluates symptom severity. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0 to 4 scale with 0=normal and 4=extreme description of the particular side effect. The total range is 0=no side effects observed to 40 = extreme of each of the 10 side effects.
Time frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
Population: Safety
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, RBP-7000 60 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 106 | 0.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 56 | 0.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 28 | 0.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 84 | 0.0 units on a scale |
| Cohort 1, RBP-7000 60 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Baseline | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 84 | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 106 | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Baseline | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 28 | 0.0 units on a scale |
| Cohort 2, RBP-7000 90 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 56 | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Baseline | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 84 | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 56 | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 106 | 0.0 units on a scale |
| Cohort 3, RBP-7000 120 mg | Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 | Day 28 | 0.0 units on a scale |