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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Reckitt Benckiser Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01677377
First received: August 27, 2012
Last updated: September 6, 2013
Last verified: June 2012
  Purpose

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


Condition Intervention Phase
Schizophrenia
Drug: Risperidone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Reckitt Benckiser Pharmaceuticals Inc.:

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


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


Estimated Enrollment: 45
Study Start Date: August 2012
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Risperidone, Comparator, Subcu injection
Risperidone 2mg oral and RBP-7000 60mg injection
Drug: Risperidone
2mg, 3mg, and 4mg oral and 60mg, 90mg, and 120mg subcutaneous injection
Active Comparator: Risperidone, Comparator, Subcutaneous
Risperidone 3mg oral and RBP-7000 90mg injection
Drug: Risperidone
2mg, 3mg, and 4mg oral and 60mg, 90mg, and 120mg subcutaneous injection
Active Comparator: Risperidone, comparator, injection
Risperidone 4mg oral and RBP-7000 120mg injection
Drug: Risperidone
2mg, 3mg, and 4mg oral and 60mg, 90mg, and 120mg subcutaneous injection

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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01677377

Locations
United States, Alaska
Woodland International Research Group, Inc.
Little Rock, Alaska, United States, 72211
United States, California
Ocean View Psychiatric Health Facility
Long Beach, California, United States, 90806
Sponsors and Collaborators
Reckitt Benckiser Pharmaceuticals Inc.
Investigators
Study Director: Philippa Whitelaw, Sr. Dir of Proj Deliver Pharmaceutical Research Associates, Inc.
Study Director: Ashley Huston, PMP Pharmaceutical Research Associates, Inc.
  More Information

No publications provided

Responsible Party: Reckitt Benckiser Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01677377     History of Changes
Other Study ID Numbers: RB-US-09-0009
Study First Received: August 27, 2012
Last Updated: September 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Reckitt Benckiser Pharmaceuticals Inc.:
Schizophrenia
Schizophrenic
Schizophrenias

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Risperidone
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 22, 2014