Back to resultsMultiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Risperidone
RBP-7000
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Schizophrenic, Schizophrenias
Eligibility Criteria
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
Sites / Locations
- Woodland International Research Group, Inc.
- Ocean View Psychiatric Health Facility
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1, RBP-7000 60 mg
Cohort 2, RBP-7000 90 mg
Cohort 3, RBP-7000 120 mg
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Secondary Outcome Measures
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.
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.
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).
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01677377
Brief Title
Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy
Official Title
A Phase 2A, Open-Label, Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, and Primary Pharmacodynamic Markers of Efficacy of 60mg, 90mg, and 120mg of Risperidone in RBP-7000 Subcutaneous Injections in Subjects With Clinically Stable Schizophrenia
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indivior Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, Schizophrenic, Schizophrenias
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1, RBP-7000 60 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2, RBP-7000 90 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3, RBP-7000 120 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Risperidone
Other Intervention Name(s)
Risperdal
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
RBP-7000
Other Intervention Name(s)
risperidone in Atrigel
Intervention Description
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.
Primary Outcome Measure Information:
Title
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
Description
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
Title
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Description
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
Title
Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Description
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
Title
Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Description
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
Title
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Description
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
Title
Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Description
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
Title
Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Description
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
Title
Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Description
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
Title
Total Risperidone PK: Percent Fluctuation Over the PK Profile
Description
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
Title
Total Risperidone PK: Swing Over the PK Profile
Description
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
Title
Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Description
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
Title
Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))
Description
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
Title
Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))
Description
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
Title
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Description
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
Title
Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Description
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
Title
Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Description
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
Title
Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Description
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
Title
Total Risperidone PK: Percent Fluctuation Over the Secondary Peak
Description
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
Title
Total Risperidone PK: Swing Over the Secondary Peak
Description
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
Title
Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Description
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
Title
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Description
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
Title
Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Description
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
Title
Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Description
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
Title
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Description
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
Title
Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Description
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
Title
Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Description
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
Title
Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Description
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
Title
Risperidone PK: Percent Fluctuation Over the PK Profile
Description
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
Title
Risperidone PK: Swing Over the PK Profile
Description
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
Title
Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Description
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
Title
Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))
Description
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
Title
Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))
Description
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
Title
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Description
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
Title
Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Description
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
Title
Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Description
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
Title
Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Description
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
Title
Risperidone PK: Percent Fluctuation Over the Secondary Peak
Description
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
Title
Risperidone PK: Swing Over the Secondary Peak
Description
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
Title
Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Description
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
Title
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Description
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
Title
9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Description
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
Title
9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Description
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
Title
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Description
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
Title
9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Description
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
Title
9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Description
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
Title
9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Description
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
Title
9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile
Description
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
Title
9-hydroxyrisperidone PK: Swing Over the PK Profile
Description
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
Title
9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Description
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
Title
9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))
Description
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
Title
9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))
Description
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
Title
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Description
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
Title
9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Description
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
Title
9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Description
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
Title
9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Description
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
Title
9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak
Description
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
Title
9-hydroxyrisperidone PK: Swing Over the Secondary Peak
Description
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
Title
9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Description
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
Secondary Outcome Measure Information:
Title
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Description
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)
Title
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Description
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)
Title
Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106
Description
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)
Title
Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106
Description
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)
Title
Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106
Description
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)
Title
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
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippa Whitelaw, Sr. Dir of Proj Deliver
Organizational Affiliation
Pharmaceutical Research Associates
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Ashley Huston, PMP
Organizational Affiliation
Pharmaceutical Research Associates
Official's Role
Study Director
Facility Information:
Facility Name
Woodland International Research Group, Inc.
City
Little Rock
State/Province
Alaska
ZIP/Postal Code
72211
Country
United States
Facility Name
Ocean View Psychiatric Health Facility
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy
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