Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy
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 Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Alaska
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Little Rock, Alaska, United States, 72211
- Woodland International Research Group, Inc.
-
-
California
-
Long Beach, California, United States, 90806
- Ocean View Psychiatric Health Facility
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: FACTORIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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EXPERIMENTAL: Cohort 1, RBP-7000 60 mg
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57.
Participants returned to 2 mg oral daily risperidone on days 85-87.
|
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.
Other Names:
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.
Other Names:
|
|
EXPERIMENTAL: Cohort 2, RBP-7000 90 mg
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57.
Participants returned to 3 mg oral daily risperidone on days 85-87.
|
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.
Other Names:
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.
Other Names:
|
|
EXPERIMENTAL: Cohort 3, RBP-7000 120 mg
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57.
Participants returned to 4 mg oral daily risperidone on days 85-87.
|
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.
Other Names:
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
Time Frame: Day 1 to Day 106
|
An adverse event (AE) is defined as any study-related event that represents a change (positive or negative) in frequency or severity from a baseline (prestudy) event (if any), regardless of the presence of causal relationship or medical significance. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the first study dose date. AEs are determined by the Investigator to be related or not related to the study drug. A serious AE (SAE) is defined by federal regulation as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Although a subject may have had 2 or more adverse experiences the subject is counted only once in a category. The same subject may appear in different categories. |
Day 1 to Day 106
|
|
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Time Frame: Day 1-2, Day 57-58
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
AUC0-24 calculated using the linear trapezoidal rule. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-2, Day 57-58
|
|
Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Time Frame: Day 1-2, Day 57-58
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
Cmax determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-2, Day 57-58
|
|
Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Time Frame: Day 1-2, Day 57-58
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
Tmax determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-2, Day 57-58
|
|
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Time Frame: Day 1-28, Day 57-84
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
AUCtau calculated using the linear trapezoidal rule. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
The average of plasma concentrations calculated as AUCtau/ tau (tau = 28 days) Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Total Risperidone PK: Percent Fluctuation Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Total Risperidone PK: Swing Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))
Time Frame: Day 1-28, Day 57-84
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
Accumulation index in terms of AUC calculated as ratio of AUCtau injection 3 / injection 1. Tau = 28 days. The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))
Time Frame: Day 1-28, Day 57-84
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
Accumulation index in terms of Cmax calculated as ratio of Cmax injection 3 / injection 1. The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Time Frame: Day 2-29, Day 58-85
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
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:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Time Frame: Day 2-29, Day 58-85
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
The average of plasma concentrations in the plateau, calculated as AUC Day 2-29/time Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Time Frame: Day 2-29, Day 58-85
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
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:
|
Day 2-29, Day 58-85
|
|
Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Total Risperidone PK: Percent Fluctuation Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Total Risperidone PK: Swing Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone:
Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Time Frame: Day 1-2, Day 57-58
|
AUC0-24 calculated using the linear trapezoidal rule. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-2, Day 57-58
|
|
Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Time Frame: Day 1-2, Day 57-58
|
Cmax determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-2, Day 57-58
|
|
Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Time Frame: Day 1-2, Day 57-58
|
Tmax determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-2, Day 57-58
|
|
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Time Frame: Day 1-28, Day 57-84
|
AUCtau calculated using the linear trapezoidal rule. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
The average of plasma concentrations calculated as AUCtau/ tau (tau = 28 days) Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Risperidone PK: Percent Fluctuation Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Risperidone PK: Swing Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))
Time Frame: Day 1-28, Day 57-84
|
Accumulation index in terms of AUC calculated as ratio of AUCtau injection 3 / injection 1. Tau = 28 days. The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))
Time Frame: Day 1-28, Day 57-84
|
Accumulation index in terms of Cmax calculated as ratio of Cmax injection 3 / injection 1. The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Time Frame: Day 2-29, Day 58-85
|
Area under plasma concentration-time curve from 24 hours (Day 2) to the last quantifiable collection during dosing interval (28 days); calculated using the linear trapezoidal rule. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Time Frame: Day 2-29, Day 58-85
|
The average of plasma concentrations in the plateau, calculated as AUC Day 2-29/time Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Time Frame: Day 2-29, Day 58-85
|
Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: Secondary Peak, Injection 1 (Day 2 - Day 29) Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Risperidone PK: Percent Fluctuation Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Risperidone PK: Swing Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Time Frame: Day 1-2, Day 57-58
|
AUC0-24 calculated using the linear trapezoidal rule. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-2, Day 57-58
|
|
9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Time Frame: Day 1-2, Day 57-58
|
Cmax determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-2, Day 57-58
|
|
9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Time Frame: Day 1-2, Day 57-58
|
Tmax determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-2, Day 57-58
|
|
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Time Frame: Day 1-28, Day 57-84
|
AUCtau calculated using the linear trapezoidal rule. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
The average of plasma concentrations calculated as AUCtau/ tau (tau = 28 days) Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
9-hydroxyrisperidone PK: Swing Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Time Frame: Day 1-28, Day 57-84
|
Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))
Time Frame: Day 1-28, Day 57-84
|
Accumulation index in terms of AUC calculated as ratio of AUCtau injection 3 / injection 1. Tau = 28 days. The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))
Time Frame: Day 1-28, Day 57-84
|
Accumulation index in terms of Cmax calculated as ratio of Cmax injection 3 / injection 1. The PK sampling schedule was:
|
Day 1-28, Day 57-84
|
|
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Time Frame: Day 2-29, Day 58-85
|
Area under plasma concentration-time curve from 24 hours (Day 2) to the last quantifiable collection during dosing interval (28 days); calculated using the linear trapezoidal rule. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Time Frame: Day 2-29, Day 58-85
|
The average of plasma concentrations in the plateau, calculated as AUC Day 2-29/time Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Time Frame: Day 2-29, Day 58-85
|
Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: Secondary Peak, Injection 1 (Day 2 - Day 29) Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
9-hydroxyrisperidone PK: Swing Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
|
9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Time Frame: Day 2-29, Day 58-85
|
Results are reported across two timeframes:
The PK sampling schedule was:
|
Day 2-29, Day 58-85
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Time Frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
The switch from oral risperidone to RBP-7000 subcutaneous injections for efficacy markers used the PANSS scores. The PANSS assessment is a medical scale designed to measure symptom severity among patients with schizophrenia. Each item is rated on a scale of 1=absent to 7=extreme. PANSS consists of three components:
The 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. |
Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
|
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Time Frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
The switch from oral risperidone to RBP-7000 subcutaneous injections for efficacy markers used CGI scores. The CGI is used in the assessment of global illness severity and change in clinical condition over time in psychiatric patients. Severity of illness is measured on a 7-point scale with 1=normal, not at all ill and 7=among the most extremely ill patients. Global improvement is measured on a 7-point scale with 1=very much improved, 4=no change and 7=very much worse as compared to the severity of illness at baseline. |
Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
|
Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106
Time Frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
The switch from oral risperidone to RBP-7000 subcutaneous injections for safety markers used AIMS. The AIMS is a scale that aids in the early detection and ongoing monitoring of tardive dyskinesia, a movement disorder that can result from long-term treatment with antipsychotic medication. By assessing the participant's body movement in specific positions requiring rotation, a psychiatrist is able to determine whether abnormal facial or body movements exist. The total score is the sum of 7 questions assessing movement plus 3 questions representing global assessments on the overall level of involuntary movement severity, incapacitation due to involuntary movement, and patient's awareness of involuntary movement. Each of the 10 questions are scored on a 0 (none) - 4 (extremely severe) scale. Plus two dental status questions are scored on a 0 (no) - 1 (yes) scale. The total score is therefore a scale of 0 (normal) - 42 (advanced tardive dyskinesia). |
Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
|
Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106
Time Frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
The switch from oral risperidone to RBP-7000 subcutaneous injections for safety markers used SAS.
The SAS is a 10-item scale used to detect the presence of drug induced parkinsonism and extrapyramidal side effects, and evaluates symptom severity.
The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness.
Items are rated for severity on a 0 to 4 scale with 0=normal and 4=extreme description of the particular side effect.
The total range is 0=no side effects observed to 40 = extreme of each of the 10 side effects.
|
Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
|
Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106
Time Frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
The BAS is a scale that detects the presence and severity of any drug induced akathisia.
The scale measures objective and subjective effects such as restlessness and awareness of restlessness, respectively.
Participants are observed while seated, then while standing and engaged in neutral conversation.
Symptoms observed during additional situations, such as participant behavior on the ward, may also be rated.
Subjective phenomena should be elicited through direct questioning of the participant.
The global clinical assessment is reported on a scale of 0 to 5, where 0 = absent and 5 = severe akathisia.
|
Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
|
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
Time Frame: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
The C-SSRS is a scale developed by the National Institute of Mental Health trial group as a counterpart to the FDA's categorization of suicidal events. It was developed by a careful review and consequent categorization of thoughts and behavior that were statistically identified as significantly related to suicidal behavior. The scale captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors throughout lifetime at screening, baseline, and for the time interval since last administration for repeat administrations during a study. This outcome reports the number of participants with suicidal ideation or behavior. |
Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Philippa Whitelaw, Sr. Dir of Proj Deliver, Pharmaceutical Research Associates
- Study Director: Ashley Huston, PMP, Pharmaceutical Research Associates
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Schizophrenia Spectrum and Other Psychotic Disorders
- Schizophrenia
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Agents
- Dopamine Agents
- Serotonin Antagonists
- Dopamine Antagonists
- Risperidone
Other Study ID Numbers
- RB-US-09-0009
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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