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Open-label, Extension Study of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in Patients With Schizophrenia

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ClinicalTrials.gov Identifier: NCT01683058
Recruitment Status : Completed
First Posted : September 11, 2012
Results First Posted : March 31, 2015
Last Update Posted : March 31, 2015
Sponsor:
Collaborators:
H. Lundbeck A/S
Otsuka America Pharmaceutical
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Tracking Information
First Submitted Date  ICMJE September 7, 2012
First Posted Date  ICMJE September 11, 2012
Results First Submitted Date  ICMJE December 23, 2014
Results First Posted Date  ICMJE March 31, 2015
Last Update Posted Date March 31, 2015
Study Start Date  ICMJE January 2013
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2015)
Percentage of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Discontinued Investigational Medicinal Product (IMP) Due to AEs, Serious TEAEs and Outcome of Death [ Time Frame: Baseline to Week 24 ]
A TEAE was defined as an AE that began after the first injection or was continuous from Baseline and was serious, study drug-related, or resulted in death.
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2012)
  • Treatment-emergent AEs (TEAEs) by severity [ Time Frame: 24 Weeks ]
    % of subjects reporting Treatment-emergent AEs (TEAEs) by severity
  • Treatment-emergent AEs potentially causally related to the IMP [ Time Frame: 24 Weeks ]
    % of Subjects reporting Treatment-emergent AEs potentially causally related to the IMP
  • Treatment-emergent AEs with an outcome of death [ Time Frame: 24 Weeks ]
    % of subjects with Treatment-emergent AEs with an outcome of death
  • Serious TEAEs [ Time Frame: 24 Weeks ]
    % of subjects reporting Serious Treatment Emergent Adverse Events
  • Discontinuations due to TEAEs [ Time Frame: 24 weeks ]
    % of subjects discontinuing due to Treatment Emergent Adverse Events
Change History Complete list of historical versions of study NCT01683058 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2015)
  • Mean Change From Baseline in Suicidal Ideation Intensity Total Score by the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline to Week 24 ]
    Data collected from C-SSRS were mapped into C-CASA. The Columbia Classification Algorithm of Suicide Assessment (C-CASA) method and C-SSRS(text in parentheses as said below) were mapped as; 1= completed suicide(completed suicide); 2= suicide attempt(actual attempt); 3= preparatory actions toward imminent suicidal behavior (interrupted attempt, aborted attempt and preparatory acts/behavior); 4= suicidal ideation(wish to die,active suicidal thought, active suicidal thought with method, active suicidal thought with intent,active suicidal thought with plan/intent); 5= self-injurious behavior, intent unknown; 6= not enough information: death; 7= non-suicidal self-injurious behavior(nonsuicidal self-injurious behavior); 8= other accident; psychiatric/medical; 9= not enough information/non-death. C-CASA category 5, 6, 8 and 9 are not applicable. For each item, each participant received an intensity score from 0(none) to 5(worst). Suicidal ideation intensity total score range from 0 to 25.
  • Mean Change From Baseline by Week by Extrapyramidal Symptoms (EPS) Evaluated Using the Simpson-Angus Scale (SAS) [ Time Frame: Baseline to Week 24 ]
    The EPS rating scales included SAS total score (range 10-50) was the sum of the rating scores for 10 items from the SAS panel. This scale consists of a list of 10 symptoms, each to be rated on a 5-point scale of severity. For each symptom, the rating which best described the patient's condition were, 1= gait; 2= arm dropping; 3= shoulder shaking; 4= elbow rigidity; 5= wrist rigidity; 6= head rotation; 8= tremor; 9= salivation; 10= akathisia.
  • Mean Change From Baseline by Week by EPS Evaluated Using the Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: Baseline to Week 24 ]
    EPS rating scale included the AIMS movement rating score (range 0-28) was the sum of the rating scores for facial and oral movements (i.e., item 1 - 4), extremity movements (i.e. item 5 - 6), and trunk movements (i.e. item 7). The symptoms for facial and oral movements were 1= muscles of facial expression, 2= lips and perioral area, 3= jaw and 4=tongue; extremity movements were, 5= upper (arms, wrists, hands, fingers), lower (legs, knees, ankles, toes), 7= neck, shoulders, hips). This scale consisted of 10 items, each to be rated on a 4-point scale of severity, and 2 questions to be answered by yes or no. To complete the scale, the patient was observed unobtrusively at rest (e.g., in waiting room). The chair used for this examination was hard, firm one without arms.
  • Mean Change From Baseline by Week by EPS Evaluated Using Barnes Akathisia Rating Scale (BARS) [ Time Frame: Baseline to Week 24 ]
    The BARS global score (range 0-5) was derived from the global clinical assessment of akathisia from the BARS panel were, 0= absent; 1= questionable; 2= mild akathisia; 3= moderate akathisia; 4= marked akathisia; 5= severe akathisia. Patients were observed while they were seated and then standing (for a minimum of 2 minutes in each position). Symptoms were observed in other situations (e.g., while engaged in neutral conversation, engaged in activity on the ward) was also rated.
  • Mean Change in Body Temperature From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The body temperature, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure, and respiratory rate that were identified based on pre-defined criteria.
  • Mean Change in Heart Rate Supine From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The heart rate supine, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure, and respiratory rate that were identified based on pre-defined criteria.
  • Mean Change in Systolic Supine Blood Pressure (BP) From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The systolic supine BP, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure, and respiratory rate that were identified based on pre-defined criteria.
  • Mean Change in Diastolic Supine BP From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The diastolic supine BP, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure and respiratory rate that were identified based on pre-defined criteria.
  • Mean Change in Heart Rate From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The heart rate sitting, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure and respiratory rate that were identified based on pre-defined criteria. Orthostatic assessments of blood pressure and heart rate were made after the participant was supine for at least 5 minutes and again after the participant was sitting for approximately 2 minutes.
  • Mean Change in Systolic BP From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The systolic sitting BP, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure and respiratory rate that were identified based on pre-defined criteria. Orthostatic assessments of blood pressure and heart rate were made after the participant was supine for at least 5 minutes and again after the participant was sitting for approximately 2 minutes.
  • Mean Change in Diastolic BP From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The diastolic sitting BP, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure and respiratory rate that were identified based on pre-defined criteria. Orthostatic assessments of blood pressure and heart rate were made after the participant was supine for at least 5 minutes and again after the participant was sitting for approximately 2 minutes.
  • Mean Change in Ventricular Rate From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The measurement ventricular rate is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, RR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.
  • Mean Change in PR Interval From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The measurement PR interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.
  • Mean Change in RR Interval From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The measurement RR interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.
  • Mean Change in QRS Interval From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The measurement QRS interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.
  • Mean Change in QT Interval From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The measurement QT interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, RR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.
  • Mean Change in QTcB Interval From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The measurement QTcB interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, RR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.
  • Mean Change in QTcF Interval From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The measurement QTcF interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, RR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.
  • Mean Change in QTcN Interval From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    The measurement QTcN interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, RR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.
  • Mean Change in Clinically Relevant Body Weight Changes From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    Clinically relevant body weight changes was one of the primary parameters to measure the safety and tolerability of individual participants. Each participant's body mass index (BMI) kilogram per square meter (kg/m2) were calculated from the screening. Body weight, BMI, and waist circumference changes were evaluated by calculating mean change from Baseline and by tabulating the incidence of ≥7% weight gain or loss.
  • Mean Change in Clinically Relevant Body Mass Index From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    Clinically relevant body mass index was one of the primary parameters to measure the safety and tolerability of individual participants. Each participant's body mass index (BMI) kilogram per square meter (kg/m2) were calculated from the screening. Body weight, BMI, and waist circumference changes were evaluated by calculating mean change from Baseline and by tabulating the incidence of ≥7% weight gain or loss.
  • Mean Change in Clinically Relevant Waist Circumference From Baseline in All Participants. [ Time Frame: Baseline to last visit ]
    Clinically relevant waist circumference was one of the primary parameters to measure the safety and tolerability of individual participants. Each participant's body mass index (BMI) kilogram per square meter (kg/m2) were calculated from the screening. Body weight, BMI, and waist circumference changes were evaluated by calculating mean change from Baseline and by tabulating the incidence of ≥7% weight gain or loss.
  • Number of Participants With Clinically Relevant Laboratory Values. [ Time Frame: Baseline to last visit ]
    The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria.
  • Number of Participants With Clinically Relevant Physical Examination. [ Time Frame: Baseline to last visit ]
    The physical examination evaluation was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in the following body systems: head, ears, eyes, nose, and throat; thorax; abdomen; urogenital; extremities; neurological; and skin and mucosae.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2012)
  • Suicide risk as assessed and classified by the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 24 Weeks ]
    Change in C-SSRS scores from baseline to end of study
  • Extrapyramidal symptoms evaluated using the Simpson-Angus Scale (SAS) [ Time Frame: 24 Weeks ]
    Change from baseline on Simpson-Angus Scale
  • Extrapyramidal symptoms evaluated using the Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: 24 Weeks ]
    Change from baseline on Abnormal Involuntary Movement Scale (AIMS)
  • Extrapyramidal symptoms evaluated using Barnes Akathisia Rating Scale (BARS) [ Time Frame: 24 Weeks ]
    Change from baseline on Barnes Akathisia Rating Scale (BARS)
  • % of subjects with clinically relevant Vital Signs [ Time Frame: 24 Weeks ]
    % of subjects with clinically relevant Vital Signs
  • % of subjects with clinically relevant ECGs [ Time Frame: 24 Weeks ]
    % of subjects with clinically relevant ECGs
  • % of subjects with clinically relevant body weight changes [ Time Frame: 24 Weeks ]
    % of subjects with clinically relevant body weight changes
  • Physical Examination Findings [ Time Frame: 24 Weeks ]
    % of patients with clinically relevant physical examination findings
  • Lab Values [ Time Frame: 24 Weeks ]
    % of subjects with clinically relevant Lab values
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open-label, Extension Study of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in Patients With Schizophrenia
Official Title  ICMJE A 26-week, Multicenter, Open-label, Extension Study of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in Patients With Schizophrenia
Brief Summary The phase 3 Trial 31-12-291 is part of the aripiprazole IM depot clinical development program and has been designed to demonstrate the efficacy and safety of aripiprazole IM depot for the treatment of adults experiencing an acute relapse of schizophrenia. Subjects receive treatment during a 12-week double-blind acute treatment phase. The current trial (31-12-297) will allow the subjects who complete Trial 291 to enter this open label trial at the investigator's discretion, where additional safety and tolerability data will be collected.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Schizophrenia
Intervention  ICMJE Drug: Aripiprazole IM Depot
Aripiprazole IM Depot 400 mg or 300 mg
Study Arms  ICMJE Experimental: Aripiprazole IM Depot
Aripiprazole IM Depot 400 mg or 300 mg once monthly (every 28 days) for 24 weeks
Intervention: Drug: Aripiprazole IM Depot
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 19, 2013)
74
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2012)
125
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male and female subjects 18 to 66 years of age, inclusive, at the time of informed consent.
  • Subjects who are able to provide written informed consent (as required by IRB/IEC) prior to the initiation of any protocol-required procedures.
  • Ability, in the opinion of the investigator, to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, and discontinuation of prohibited concomitant medication, and to be reliably rated on assessment scales.
  • Subjects who have met the completion criteria in the 31-12-291 registrational trial for the acute treatment of adults with schizophrenia
  • Subjects who, in the investigator's judgment, require chronic treatment with antipsychotic medication and would benefit from extended treatment with an IM depot formulation.
  • Outpatient status at the Week 12 in Trial 291, with the exception of those subjects eligible to enter Trial 297 due to a positive interim analysis.

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 the last dose of trial medication. Sexually active Women 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 the 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 experiencing acute depressive symptoms within the past 30 days, according to the investigator's opinion, that requires treatment with an antidepressant.
  • Subjects who are anticipated needing CYP2D6 or CYP3A4 inhibitors or CYP3A4 inducers during the course of the trial.
  • Subjects with a significant risk of violent behavior; who represent a risk of committing suicide; or who in the clinical judgment of the investigator present a serious risk of suicide.
  • Subjects requiring any antipsychotic(s) other than aripiprazole IM depot after completion of Trial 291.
  • Subjects likely to require prohibited concomitant therapy during the trial
  • Laboratory test and ECG results which are exclusionary
  • Any subject who, in the opinion of the investigator or medical monitor, should not participate in the trial
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 66 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Croatia,   Latvia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01683058
Other Study ID Numbers  ICMJE 31-12-297
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Otsuka Pharmaceutical Development & Commercialization, Inc.
Study Sponsor  ICMJE Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators  ICMJE
  • H. Lundbeck A/S
  • Otsuka America Pharmaceutical
Investigators  ICMJE Not Provided
PRS Account Otsuka Pharmaceutical Development & Commercialization, Inc.
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP