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Trial of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in the Acute Treatment of Adults With Schizophrenia

Primary Purpose

Schizophrenia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Aripiprazole IM Depot
Placebo
Sponsored by
Otsuka Pharmaceutical Development & Commercialization, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male and female subjects 18 to 65 years of age, inclusive, at time of informed consent.
  • Subjects with a diagnosis of schizophrenia for at least 1 year as defined by DSM-IV-TR criteria and confirmed by the MINI for Schizophrenia and Psychotic Disorders Studies.
  • Subjects with a stable living environment when not in hospital.
  • Subjects who would benefit from hospitalization or continued hospitalization for treatment of a current acute relapse of schizophrenia at trial entry.

  • Subjects who are experiencing an acute exacerbation of psychotic symptoms and marked deterioration of usual function as demonstrated by meeting BOTH of the following at screening and baseline:

    • Currently experiencing an acute exacerbation of psychotic symptoms accompanied by significant deterioration in the subject's clinical and/or functional status from their baseline clinical presentation with a Positive and Negative Syndrome Scale (PANSS) Total Score ≥ 80 AND

    • Specific psychotic symptoms on the PANSS as measured by a score of > 4 on each of the following items (possible scores of 1 to 7 for each item)

      • Conceptual disorganization (P2)
      • Hallucinatory behavior (P3)
      • Suspiciousness/persecution (P6)
      • Unusual thought content (G9)
  • Subjects who have received previous outpatient antipsychotic treatment at an adequate dose for an adequate duration and who showed a previous good response to such antipsychotic treatment (other than clozapine) in last 12 months.
  • Subjects with a history of relapse and/or exacerbation of symptoms when not receiving antipsychotic treatment, excluding current episode.
  • Subjects willing to discontinue all prohibited psychotropic medications to meet protocol required washouts prior to and during trial period.
  • BMI less ≤ 40 kg/m2 (morbid obesity) at screening.
  • Subjects who are able to provide written informed consent.
  • Ability to understand the nature of trial and follow protocol requirements.

Exclusion Criteria:

  • Sexually active males of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 180 days after last dose of trial medication. Sexually active females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 150 days after last dose of trial medication.
  • Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP in this trial.
  • Subjects with improvement of ≥ 30% in total PANSS score between the screening and baseline assessments. - Subjects presenting with a first episode of schizophrenia - Subjects hospitalized for ≥ 30 days out of the last 90 days prior to screening visit. Subjects who have been hospitalized > 5 days for current acute episode at the time of screening visit
  • Subjects with schizophrenia who are considered resistant/refractory to antipsychotic treatment Subjects who have a history of response to clozapine treatment only.
  • Subjects with a current DSM-IV-TR Axis I diagnosis other than schizophrenia Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder or mental retardation.
  • Subjects experiencing acute depressive symptoms within past 30 days that require treatment with an antidepressant.
  • Subjects with a significant risk of violent behavior; who represent a risk of committing suicide as indicated by any suicidal ideation within the last 1 month or any suicidal behaviors within the last year; or who present a serious risk of suicide.
  • Subjects with clinically significant tardive dyskinesia,.
  • Subjects with severe akathisia.
  • Subjects who have met DSM-IV-TR criteria for substance abuse with past 3 months prior to screening or dependence within past 6 months; including alcohol and benzodiazepines, but excluding caffeine and nicotine.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Aripiprazole IM Depot

Placebo

Arm Description

Aripiprazole IM Depot 400 mg, with allowed decrease to 300 mg for safety and return to 400 mg for efficacy if needed, every four weeks for 12 weeks

Matching placebo

Outcomes

Primary Outcome Measures

Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score.
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome). The primary statistical comparison was performed using the Mixed Model Repeated Measure (MMRM) approach.

Secondary Outcome Measures

Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score.
The severity of illness for each participants were rated using the CGI-S scale. The study physician were to answer the following question: "Considering your total experience with this particular population, how mentally ill is the patient at this time?" Response choices included were: 0= not assessed; 1= normal; not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants.
Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score.
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS Positive Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).
Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score.
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated- absence of symptoms and a score of 7 indicated- extremely severe symptoms. The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs were: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. PANSS Negative Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).
Mean Change From Baseline to Endpoint in Personal and Social Performance Scale (PSP) Score.
The PSP was a validated clinician scale that measured personal and social functionining in 4 domains: socially useful activities eg, work and study), personal and social relationships, self-care, disturbing and aggressive behaviours. Impairement in each of these domains was rated as absent, mild, manifest, marked, severe, or very severe. These ratings were then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval and the study physician's judgement to determine the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented varying degrees of disability (31 to 70) and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision.
Mean Clinical Global Impression-Improvement Scale (CGI-I) Score at Endpoint.
The severity of illness for each participants were rated using the CGI-S scale. The study physician were to answer the following question: "Considering your total experience with this particular population, how mentally ill is the patient at this time?" Response choices included were: 0= not assessed; 1= normal; not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants.
Responder Rate Based on PANSS Total Score.
Responder rate was defined as ≥30% reduction from Baseline in PANSS Total Score. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

Full Information

First Posted
August 9, 2012
Last Updated
February 12, 2015
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
H. Lundbeck A/S, Otsuka America Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT01663532
Brief Title
Trial of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in the Acute Treatment of Adults With Schizophrenia
Official Title
A 12-week, Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in the Acute Treatment of Adults With Schizophrenia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
H. Lundbeck A/S, Otsuka America Pharmaceutical

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary purpose of this study is to evaluate the overall efficacy of aripiprazole intramuscular (IM) depot as acute treatment in subjects with schizophrenia. The secondary purpose is to evaluate the safety and tolerability of aripiprazole IM depot administered every 4 weeks for 12 weeks to adult subjects with schizophrenia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
340 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Aripiprazole IM Depot
Arm Type
Experimental
Arm Description
Aripiprazole IM Depot 400 mg, with allowed decrease to 300 mg for safety and return to 400 mg for efficacy if needed, every four weeks for 12 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo
Intervention Type
Drug
Intervention Name(s)
Aripiprazole IM Depot
Other Intervention Name(s)
OPC-14597, Lu AF41155
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching Placebo
Primary Outcome Measure Information:
Title
Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score.
Description
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome). The primary statistical comparison was performed using the Mixed Model Repeated Measure (MMRM) approach.
Time Frame
Baseline to Week 10
Secondary Outcome Measure Information:
Title
Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score.
Description
The severity of illness for each participants were rated using the CGI-S scale. The study physician were to answer the following question: "Considering your total experience with this particular population, how mentally ill is the patient at this time?" Response choices included were: 0= not assessed; 1= normal; not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants.
Time Frame
Baseline to Week 10
Title
Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score.
Description
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS Positive Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).
Time Frame
Baseline to Week 10
Title
Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score.
Description
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated- absence of symptoms and a score of 7 indicated- extremely severe symptoms. The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs were: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. PANSS Negative Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).
Time Frame
Baseline to Week 10
Title
Mean Change From Baseline to Endpoint in Personal and Social Performance Scale (PSP) Score.
Description
The PSP was a validated clinician scale that measured personal and social functionining in 4 domains: socially useful activities eg, work and study), personal and social relationships, self-care, disturbing and aggressive behaviours. Impairement in each of these domains was rated as absent, mild, manifest, marked, severe, or very severe. These ratings were then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval and the study physician's judgement to determine the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented varying degrees of disability (31 to 70) and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision.
Time Frame
Week 10
Title
Mean Clinical Global Impression-Improvement Scale (CGI-I) Score at Endpoint.
Description
The severity of illness for each participants were rated using the CGI-S scale. The study physician were to answer the following question: "Considering your total experience with this particular population, how mentally ill is the patient at this time?" Response choices included were: 0= not assessed; 1= normal; not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants.
Time Frame
Week 10
Title
Responder Rate Based on PANSS Total Score.
Description
Responder rate was defined as ≥30% reduction from Baseline in PANSS Total Score. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame
Week 10

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 subjects 18 to 65 years of age, inclusive, at time of informed consent. Subjects with a diagnosis of schizophrenia for at least 1 year as defined by DSM-IV-TR criteria and confirmed by the MINI for Schizophrenia and Psychotic Disorders Studies. Subjects with a stable living environment when not in hospital. Subjects who would benefit from hospitalization or continued hospitalization for treatment of a current acute relapse of schizophrenia at trial entry. Subjects who are experiencing an acute exacerbation of psychotic symptoms and marked deterioration of usual function as demonstrated by meeting BOTH of the following at screening and baseline: Currently experiencing an acute exacerbation of psychotic symptoms accompanied by significant deterioration in the subject's clinical and/or functional status from their baseline clinical presentation with a Positive and Negative Syndrome Scale (PANSS) Total Score ≥ 80 AND Specific psychotic symptoms on the PANSS as measured by a score of > 4 on each of the following items (possible scores of 1 to 7 for each item) Conceptual disorganization (P2) Hallucinatory behavior (P3) Suspiciousness/persecution (P6) Unusual thought content (G9) Subjects who have received previous outpatient antipsychotic treatment at an adequate dose for an adequate duration and who showed a previous good response to such antipsychotic treatment (other than clozapine) in last 12 months. Subjects with a history of relapse and/or exacerbation of symptoms when not receiving antipsychotic treatment, excluding current episode. Subjects willing to discontinue all prohibited psychotropic medications to meet protocol required washouts prior to and during trial period. BMI less ≤ 40 kg/m2 (morbid obesity) at screening. Subjects who are able to provide written informed consent. Ability to understand the nature of trial and follow protocol requirements. Exclusion Criteria: Sexually active males of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 180 days after last dose of trial medication. Sexually active females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 150 days after last dose of trial medication. Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP in this trial. Subjects with improvement of ≥ 30% in total PANSS score between the screening and baseline assessments. - Subjects presenting with a first episode of schizophrenia - Subjects hospitalized for ≥ 30 days out of the last 90 days prior to screening visit. Subjects who have been hospitalized > 5 days for current acute episode at the time of screening visit Subjects with schizophrenia who are considered resistant/refractory to antipsychotic treatment Subjects who have a history of response to clozapine treatment only. Subjects with a current DSM-IV-TR Axis I diagnosis other than schizophrenia Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder or mental retardation. Subjects experiencing acute depressive symptoms within past 30 days that require treatment with an antidepressant. Subjects with a significant risk of violent behavior; who represent a risk of committing suicide as indicated by any suicidal ideation within the last 1 month or any suicidal behaviors within the last year; or who present a serious risk of suicide. Subjects with clinically significant tardive dyskinesia,. Subjects with severe akathisia. Subjects who have met DSM-IV-TR criteria for substance abuse with past 3 months prior to screening or dependence within past 6 months; including alcohol and benzodiazepines, but excluding caffeine and nicotine.
Facility Information:
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72201
Country
United States
City
Springdale
State/Province
Arkansas
ZIP/Postal Code
72764
Country
United States
City
Anaheim
State/Province
California
ZIP/Postal Code
92805
Country
United States
City
Carson
State/Province
California
ZIP/Postal Code
90746
Country
United States
City
Escondido
State/Province
California
ZIP/Postal Code
92025
Country
United States
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
City
Long Beach
State/Province
California
ZIP/Postal Code
90813
Country
United States
City
National City
State/Province
California
ZIP/Postal Code
91950
Country
United States
City
Oakland
State/Province
California
ZIP/Postal Code
94612
Country
United States
City
Oceanside
State/Province
California
ZIP/Postal Code
92056
Country
United States
City
Pico Rivera
State/Province
California
ZIP/Postal Code
90660
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92102
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
City
Santa Ana
State/Province
California
ZIP/Postal Code
92701
Country
United States
City
Sherman Oaks
State/Province
California
ZIP/Postal Code
91403
Country
United States
City
Denver
State/Province
Colorado
ZIP/Postal Code
80209
Country
United States
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20016
Country
United States
City
Bradenton
State/Province
Florida
ZIP/Postal Code
34208
Country
United States
City
Ft. Lauderdale
State/Province
Florida
ZIP/Postal Code
33301
Country
United States
City
Ft. Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
City
Ft. Lauderdale
State/Province
Florida
ZIP/Postal Code
33334
Country
United States
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
City
Kissimmee
State/Province
Florida
ZIP/Postal Code
34741
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32810
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
City
Hoffman Estates
State/Province
Illinois
ZIP/Postal Code
60169
Country
United States
City
Lake Charles
State/Province
Louisiana
ZIP/Postal Code
70629
Country
United States
City
Flowood
State/Province
Mississippi
ZIP/Postal Code
39232
Country
United States
City
St. Charles
State/Province
Missouri
ZIP/Postal Code
63304
Country
United States
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63118
Country
United States
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63128
Country
United States
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
City
Marlton
State/Province
New Jersey
ZIP/Postal Code
08053
Country
United States
City
Holliswood
State/Province
New York
ZIP/Postal Code
11423
Country
United States
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19139
Country
United States
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29407
Country
United States
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
City
Austin
State/Province
Texas
ZIP/Postal Code
78754
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75243
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77007
Country
United States
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
City
Popovaca
ZIP/Postal Code
44317
Country
Croatia
City
Zagreb
ZIP/Postal Code
10090
Country
Croatia
City
Daugavpils
ZIP/Postal Code
LV-5417
Country
Latvia
City
Jelgava
ZIP/Postal Code
LV-3008
Country
Latvia
City
Liepaja
ZIP/Postal Code
LV-3401
Country
Latvia
City
Strenci
ZIP/Postal Code
LV-4730
Country
Latvia

12. IPD Sharing Statement

Citations:
PubMed Identifier
25188501
Citation
Kane JM, Peters-Strickland T, Baker RA, Hertel P, Eramo A, Jin N, Perry PP, Gara M, McQuade RD, Carson WH, Sanchez R. Aripiprazole once-monthly in the acute treatment of schizophrenia: findings from a 12-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014 Nov;75(11):1254-60. doi: 10.4088/JCP.14m09168.
Results Reference
derived

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Trial of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in the Acute Treatment of Adults With Schizophrenia

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