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Risperdal Consta for Bipolar Disorder

Primary Purpose

Bipolar I Disorder

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Injectable Risperidone (Consta) or oral antipsychotic
Sponsored by
University of Pittsburgh
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar I Disorder focused on measuring Bipolar I Disorder, Risperidone Consta - Long Acting Injection, Oral second generation antipsychotic agents

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: DSM-IV - TR diagnoses of bipolar disorder (I or II or NOS). Age 18 to 70 years Men or women Any Ethnicity Currently receiving or willing to receive treatment at sites associated with the Western Psychiatric Institute and Clinic -University of Pittsburgh Medical Center (inpatient or ambulatory) or Mon Yough Community Services, Inc. or at Mayview State Hospital, Bridgeville, PA (inpatient) Able to provide competent and sign an informed consent document It is clinically appropriate in the eligible individual to consider antipsychotic treatment for at least 15 months (clinician and investigator determined) It is clinically appropriate to switch antipsychotic treatment to one of the second generation antipsychotic agents being evaluated in this study. There is no known contraindication for the use of either risperidone or for more than two of the antipsychotic agents being considered in the study (Investigator determined) At entry (at the screening visit, and just prior to randomization) Y-MRS (Young-Mania rating scale, Young et al., 1978) total score > 15 in bipolar disorder patients entering in a manic or mixed or hypomanic or NOS episode. Either life-time or current comorbid substance abuse or dependence is permitted (unless the Investigator and referring physician opines the substance abuse is likely to significantly interfere with either the diagnosis of the Axis I condition or to compromise patients safety due to withdrawal issues (Investigator determined). Screening physical and laboratory/EKG procedures are within acceptable limits Exclusion Criteria: Actively suicidal or dangerous to others (Investigator opines that it is inappropriate to involve the potential subject in the study) Pregnant or lactating women Women in the reproductive age group who are not using any acceptable contraception (abstinence is not acceptable) or intend to become pregnant during the trial Subjects who are likely to face incarceration during the study duration (and for those already in the study, the continued participation of such subjects will be evaluated on a case-by-case basis) Patients currently receiving clozapine (or within six weeks prior to randomization) are ineligible for the study Subjects currently receiving a depot neuroleptic injectable agent, or within 2 injection cycles of receiving the injection prior to randomization. Allergy or serious side effects (for instance - neuroleptic malignant syndrome) to either risperidone or to more than two of the other second-generation antipsychotic agents that have been approved for use in the U.S.A. (olanzapine, quetiapine, ziprasidone, aripiprazole-per investigator and referring clinician). Treatment resistance to either risperidone, or to more than two of the other antipsychotic agents in this trial (olanzapine, quetiapine, ziprasidone, aripiprazole). This is the first episode of mania, mixed or hypomania for patients. Current (or within one month prior to randomization) participation in an investigational drug/device study. Currently participating in another study that would confound the present study objectives (per investigator)

Sites / Locations

  • Mayview State Hospital
  • Dubois Regional Medical Center
  • Mon-Yough Community Services, Inc.
  • Western Psychiatric Institute and Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1

2

Arm Description

Oral Risperidone followed by Long acting Risperidone injections (Consta)

Oral second generation antipsychotic agents other than clozapine or risperidone (olanzapine, quetiapine, ziprasidone, aripiprazole)

Outcomes

Primary Outcome Measures

Evaluate the Number of Clinical Events (Pooled) Occurring Between 3-15 Months Following a Switch/Stabilization of the Antipsychotic Agents Among Patients Who Receive Either Risperidal Consta or One of the 4 Marketed 2nd Generation Antipsychotic Agents.

Secondary Outcome Measures

BMI
BMI at baseline and at end of 15 months for Risperidone LAI and oral AAP groups
Number of Participants With Treatment - Emergent Hyperglycemia
Number of participants with hyperglycemia based on safety labs
Number of Participants With Treatment Emergent Hyperlipidemia
Number of participants with Hyperlipidemia as determined by safety labs

Full Information

First Posted
September 12, 2005
Last Updated
March 17, 2016
Sponsor
University of Pittsburgh
Collaborators
Janssen Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00177164
Brief Title
Risperdal Consta for Bipolar Disorder
Official Title
A Random Assignment,Parallel Group, Open Label Comparison of Clinical Outcomes and Resource Utilization Among Bipolar Disorder Patients Receiving Either Long Acting Injectable Risperidone Microspheres (Risperdal Consta® ) or Other Second Generation Oral Antipsychotic Agents: A 15 Month Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
November 2003 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pittsburgh
Collaborators
Janssen Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
We recruited 50 consenting adult subjects with DSM-IV TR diagnoses of bipolar disorder who were about to initiate or switch their current antipsychotic agent. Only 48 patients (23 in the risperidone LAI group and 25 in the oral AAP group) contributed data to the assessments. Patients were titrated and cross-tapered during a 3 month titration and stabilization phase. They were followed for an additional 12 months. Clinical outcomes such as study drop out, adverse events, worsening of symptoms, crisis interventions, need for additional medication, hospitalizations etc. were evaluated from months 3 to 15. The numbers of clinical events (pooled) will be used to evaluate if the long acting injectable form of risperidone has an advantage over the oral second generation antipsychotic agents in terms of treatment continuity and clinical stability.
Detailed Description
OBJECTIVE: To evaluate if a long acting injectable form of risperidone offers clinical advantages over comparison oral second generation antipsychotic agents following titration and stabilization in bipolar subjects. In keeping with current practice, it is expected the vast majority of patients will also be receiving either lithium or valproate or other anticonvulsants. Following the stabilization phase several clinical events will be evaluated for up to 15 months in the two treatment groups to examine differences in clinical outcomes between those receiving the injectable versus oral medicines. RESEARCH PLAN: We intend to recruit 50 consenting adult subjects with DSM-IV TR diagnoses of bipolar disorder who are about to initiate or to switch their antipsychotic agent. Patients will be titrated and cross-tapered during a 3 month titration and stabilization phase. Those who transition successfully and show some improvement will be followed for an additional 12 months. Clinical outcomes such as study drop out, adverse events, worsening of symptoms, crisis interventions, need for additional medication, hospitalizations etc. will be evaluated from months 3 to 15. The numbers of clinical events (pooled) will be used to evaluate if the long acting injectable form of risperidone has an advantage over the oral second generation antipsychotic agents in terms of treatment continuity and clinical stability. METHODS: An open design, but treatment to either the long acting risperidone or to the oral second generation antipsychotic agents is randomly assigned. A board independent of the day-to-day clinical events will code the primary clinical outcomes of interest without knowledge of treatment assignment. The board will be provided clinical summaries of these events without revealing the treatment assignment. SIGNIFICANCE: The use of a long acting injectable second generation antipsychotic agent may offer advantages of treatment continuity and adherence in bipolar patients permitting improved clinical stability and improved psychosocial and functional outcomes. Such stability is difficult to achieve in the face of frequent treatment discontinuations seen with oral agents. The improved tolerability of the second generation antipsychotic agents may change the perception of long acting injections. For instance, these agents are likely to be more acceptable to patients, families and clinicians and therefore likely be used much sooner in the treatment algorithms of bipolar patients than in the past. This study will provide a treatment effect size to statistically power future comparisons of long-acting injectable vs. oral antipsychotic agents in persons with bipolar disorder

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar I Disorder
Keywords
Bipolar I Disorder, Risperidone Consta - Long Acting Injection, Oral second generation antipsychotic agents

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Oral Risperidone followed by Long acting Risperidone injections (Consta)
Arm Title
2
Arm Type
Active Comparator
Arm Description
Oral second generation antipsychotic agents other than clozapine or risperidone (olanzapine, quetiapine, ziprasidone, aripiprazole)
Intervention Type
Drug
Intervention Name(s)
Injectable Risperidone (Consta) or oral antipsychotic
Other Intervention Name(s)
Long actiing risperidone injection (Consta), oral risperidone (risperdal)., Olanzapine (Zyprexa), Quetiapine (Seroquel), Ziprasidone (Geodon), Aripiprazole (Ablify)
Intervention Description
Injectable Risperidone (Consta) from 12.5 to 50 mg q 2 weeks Oral antipsychotic agents, olanzapine, quetiapine, ziprasidone, aripiprazole in doses approved in the US for bipolar disorder
Primary Outcome Measure Information:
Title
Evaluate the Number of Clinical Events (Pooled) Occurring Between 3-15 Months Following a Switch/Stabilization of the Antipsychotic Agents Among Patients Who Receive Either Risperidal Consta or One of the 4 Marketed 2nd Generation Antipsychotic Agents.
Time Frame
Upto 15 months
Secondary Outcome Measure Information:
Title
BMI
Description
BMI at baseline and at end of 15 months for Risperidone LAI and oral AAP groups
Time Frame
baseline to end of 15 months
Title
Number of Participants With Treatment - Emergent Hyperglycemia
Description
Number of participants with hyperglycemia based on safety labs
Time Frame
from baseline to end of 15 months
Title
Number of Participants With Treatment Emergent Hyperlipidemia
Description
Number of participants with Hyperlipidemia as determined by safety labs
Time Frame
from baseline to end of 15 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: DSM-IV - TR diagnoses of bipolar disorder (I or II or NOS). Age 18 to 70 years Men or women Any Ethnicity Currently receiving or willing to receive treatment at sites associated with the Western Psychiatric Institute and Clinic -University of Pittsburgh Medical Center (inpatient or ambulatory) or Mon Yough Community Services, Inc. or at Mayview State Hospital, Bridgeville, PA (inpatient) Able to provide competent and sign an informed consent document It is clinically appropriate in the eligible individual to consider antipsychotic treatment for at least 15 months (clinician and investigator determined) It is clinically appropriate to switch antipsychotic treatment to one of the second generation antipsychotic agents being evaluated in this study. There is no known contraindication for the use of either risperidone or for more than two of the antipsychotic agents being considered in the study (Investigator determined) At entry (at the screening visit, and just prior to randomization) Y-MRS (Young-Mania rating scale, Young et al., 1978) total score > 15 in bipolar disorder patients entering in a manic or mixed or hypomanic or NOS episode. Either life-time or current comorbid substance abuse or dependence is permitted (unless the Investigator and referring physician opines the substance abuse is likely to significantly interfere with either the diagnosis of the Axis I condition or to compromise patients safety due to withdrawal issues (Investigator determined). Screening physical and laboratory/EKG procedures are within acceptable limits Exclusion Criteria: Actively suicidal or dangerous to others (Investigator opines that it is inappropriate to involve the potential subject in the study) Pregnant or lactating women Women in the reproductive age group who are not using any acceptable contraception (abstinence is not acceptable) or intend to become pregnant during the trial Subjects who are likely to face incarceration during the study duration (and for those already in the study, the continued participation of such subjects will be evaluated on a case-by-case basis) Patients currently receiving clozapine (or within six weeks prior to randomization) are ineligible for the study Subjects currently receiving a depot neuroleptic injectable agent, or within 2 injection cycles of receiving the injection prior to randomization. Allergy or serious side effects (for instance - neuroleptic malignant syndrome) to either risperidone or to more than two of the other second-generation antipsychotic agents that have been approved for use in the U.S.A. (olanzapine, quetiapine, ziprasidone, aripiprazole-per investigator and referring clinician). Treatment resistance to either risperidone, or to more than two of the other antipsychotic agents in this trial (olanzapine, quetiapine, ziprasidone, aripiprazole). This is the first episode of mania, mixed or hypomania for patients. Current (or within one month prior to randomization) participation in an investigational drug/device study. Currently participating in another study that would confound the present study objectives (per investigator)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
K.N. Roy Chengappa, MD
Organizational Affiliation
Western Psychiatric Institute and Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayview State Hospital
City
Bridgeville
State/Province
Pennsylvania
ZIP/Postal Code
15017-1599
Country
United States
Facility Name
Dubois Regional Medical Center
City
Dubois
State/Province
Pennsylvania
ZIP/Postal Code
15801
Country
United States
Facility Name
Mon-Yough Community Services, Inc.
City
McKeesport
State/Province
Pennsylvania
ZIP/Postal Code
15132
Country
United States
Facility Name
Western Psychiatric Institute and Clinic
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213-2593
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25385032
Citation
Chengappa KN, Turkin SR, Schlicht PJ, Murphy SL, Brar JS, Fagiolini A, Houck PR, Garbutt RG, Fredrick N. A Pilot, 15-month, randomised effectiveness trial of Risperidone long-acting injection (RLAI) versus oral atypical antipsychotic agents (AAP) in persons with bipolar disorder. Acta Neuropsychiatr. 2010 Apr;22(2):68-80. doi: 10.1111/j.1601-5215.2010.00458.x.
Results Reference
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Risperdal Consta for Bipolar Disorder

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