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

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

Overview[ - collapse ][ - ]

Purpose	Evaluate the safety and tolerability of multiple subcutaneous injections of various dosages of risperidone with clinically stable schizophrenia
Condition	Schizophrenia
Intervention	Drug: Risperidone
Phase	Phase 2
Sponsor	Reckitt Benckiser Pharmaceuticals Inc.
Responsible Party	Reckitt Benckiser Pharmaceuticals Inc.
ClinicalTrials.gov Identifier	NCT01677377
First Received	August 27, 2012
Last Updated	September 6, 2013
Last verified	June 2012

Tracking Information[ + expand ][ + ]

First Received Date	August 27, 2012
Last Updated Date	September 6, 2013
Start Date	August 2012
Estimated Primary Completion Date	October 2013
Current Primary Outcome Measures	To assess the safety and tolerability of multiple subcutaneous injections of RBP-7000 [Time Frame: Day -14, Day 1, up to Day 106] [Designated as safety issue: Yes]Safety variables to be analyzed are: adverse events, local injection site tolerability, concomitant medications, changes in clinical laboratory results, vital sign measurements, 12-lead electrocardiograms, physical examination results, body weights, and monitoring of extrapyramidal symptoms using neurological and clinical symptom assessments To evaluate the pharmacokinetic (PK) profiles of risperidone [Time Frame: Day 1, Day 87, up to Day 106] [Designated as safety issue: Yes]To evaluate the pharmacokinetic profiles of risperidone, 9-hydroxyrisperidone, and total active moiety after multiple subcutaneous injections
Current Secondary Outcome Measures	To evaluate switch from oral to subcutaneous injection of risperidone [Time Frame: Day -14, Day 1, up to Day 106] [Designated as safety issue: Yes]To evaluate the switch from oral risperidone to RBP-7000 subcutaneous injections for efficacy markers using the positive and negative Syndrome Scale and Clinical Global Impression Scale for Schizophrenia as the primary markers of efficacy To evaluate switch from oral to subcutaneous injection of risperidone [Time Frame: Day -14, Day 1, up to Day 106] [Designated as safety issue: Yes]To evaluate the switch from oral risperidone to RBP-7000 subcutaneous injections for efficacy markers using the Abnormal Involuntary Movement Scale for Tardive Dyskinesia, Simpson-Angus Scale, Barnes Akathisia Scale, and Columbia-Suicide Severity Rating Scale

Descriptive Information[ + expand ][ + ]

Brief Title	Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy
Official Title	Phase 2A Study as an Open Label, Multiple Ascending Dose With Randomized Subjects to Receive a Single Dose of One of Three Dose Levels
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 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
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Schizophrenia
Intervention	Drug: Risperidone 2mg, 3mg, and 4mg oral and 60mg, 90mg, and 120mg subcutaneous injection
Study Arm (s)	Active Comparator: Risperidone, Comparator, Subcu injection Risperidone 2mg oral and RBP-7000 60mg injection Active Comparator: Risperidone, Comparator, Subcutaneous Risperidone 3mg oral and RBP-7000 90mg injection Active Comparator: Risperidone, comparator, injection Risperidone 4mg oral and RBP-7000 120mg injection

Recruitment Information[ + expand ][ + ]

Recruitment Status	Enrolling by invitation
Estimated Enrollment	45
Estimated Completion Date	October 2013
Estimated Primary Completion Date	September 2013
Eligibility Criteria	Inclusion Criteria: - Male and female - > 18 to < 65 years - Diagnosis of paranoid, residual, or undifferentiated schizophrenia as defined by 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 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 CYP2DD6 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 oof normal and/or 2) alanine aminotransferase or aspartate aminotransferase >2x upper limit of normal 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 (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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01677377
Other Study ID Numbers	RB-US-09-0009
Has Data Monitoring Committee	No
Information Provided By	Reckitt Benckiser Pharmaceuticals Inc.
Study Sponsor	Reckitt Benckiser Pharmaceuticals Inc.
Collaborators	Not Provided
Investigators	Study Director: Philippa Whitelaw, Sr. Dir of Proj Deliver Pharmaceutical Research Associates, Inc.Study Director: Ashley Huston, PMP Pharmaceutical Research Associates, Inc.
Verification Date	June 2012

Locations[ + expand ][ + ]