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

Schizophrenia Clinical Trial

Official title:

A 26-week, Multicenter, Open-label, Extension Study of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in Patients With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01683058
• Other study ID #: 31-12-297
• Status: Completed
• Phase: Phase 3
• First received: September 7, 2012
• Last updated: March 25, 2015
• Start date: January 2013
• Est. completion date: February 2014

Study information

• Verified date: March 2015
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 66 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Aripiprazole IM Depot
Aripiprazole IM Depot 400 mg or 300 mg

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.	H. Lundbeck A/S, Otsuka America Pharmaceutical

Countries where clinical trial is conducted

United States,  Croatia,  Latvia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Baseline to Week 24	Yes
Secondary	Mean Change From Baseline in Suicidal Ideation Intensity Total Score by the Columbia Suicide Severity Rating Scale (C-SSRS)	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.	Baseline to Week 24	Yes
Secondary	Mean Change From Baseline by Week by Extrapyramidal Symptoms (EPS) Evaluated Using the Simpson-Angus Scale (SAS)	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.	Baseline to Week 24	Yes
Secondary	Mean Change From Baseline by Week by EPS Evaluated Using the Abnormal Involuntary Movement Scale (AIMS)	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.	Baseline to Week 24	Yes
Secondary	Mean Change From Baseline by Week by EPS Evaluated Using Barnes Akathisia Rating Scale (BARS)	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.	Baseline to Week 24	Yes
Secondary	Mean Change in Body Temperature From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in Heart Rate Supine From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in Systolic Supine Blood Pressure (BP) From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in Diastolic Supine BP From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in Heart Rate From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in Systolic BP From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in Diastolic BP From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in Ventricular Rate From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in PR Interval From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in RR Interval From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in QRS Interval From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in QT Interval From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in QTcB Interval From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in QTcF Interval From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in QTcN Interval From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in Clinically Relevant Body Weight Changes From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in Clinically Relevant Body Mass Index From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Mean Change in Clinically Relevant Waist Circumference From Baseline in All Participants.	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.	Baseline to last visit	Yes
Secondary	Number of Participants With Clinically Relevant Laboratory Values.	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.	Baseline to last visit	Yes
Secondary	Number of Participants With Clinically Relevant Physical Examination.	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.	Baseline to last visit	Yes