Safety and Tolerability Study of Aripiprazole IM Depot in Adult Subjects With Schizophrenia

Study Overview
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Brief Summary
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To determine the safety and tolerability of multiple-dose administrations of aripiprazole intramuscular (IM) depot in the deltoid muscle in adult subjects with schizophrenia

Detailed Description
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This is a trial designed to assess the safety and tolerability of multiple-dose administrations of aripiprazole intramuscular (IM) depot in the deltoid muscle in adult subjects with schizophrenia. The trial consists of a 113 day treatment period with a 28 day followup. The trial population will include male and female subjects between 18 and 64 years (inclusive), with a current diagnosis of schizophrenia as defined by DSM-IV-TR criteria and a prior history of tolerating aripiprazole per investigator's judgement.

Official Title
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An Open-label, Multiple Dose, Safety and Tolerability Study of Aripiprazole IM Depot Administered in the Deltoid Muscle in Adult Subjects With Schizophrenia

Conditions
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Schizophrenia, Mental Disorder, Nervous System Diseases

Intervention / Treatment
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* Drug: Aripiprazole, OPC-14597


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female individuals between 18 and 64 years, inclusive, at the time of informed consent. Prior history of tolerating aripiprazole per investigator's judgement. Exclusion Criteria: Subjects who have met DSMV-IV-TR criteria for substance dependence within the past 180 days. Subjects who use more than one antipsychotic medication at screening. Use of any CYP2D6 and CYP3A4 inhibitors, or CYP3A4 inducers within 14 days prior to dosing and for the duration of the trial. Subjects who participated in any clinical trial involving a psychotropic medication within 1 month prior to enrollment. Subjects currently in an acute relapse of schizophrenia. Subjects with a current DSMV-IV-TR diagnosis other than schizophrenia. Subjects who are considered treatment-resistant to antipsychotic medications.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Gluteal Injection<br> | Drug: Aripiprazole, OPC-14597<br>* 5 monthly applications of 400 mg of aripiprazole IM depot, where the first application is in the gluteal or deltoid muscle followed by 4 monthly administrations to the deltoid muscle<br>|
| Other: Deltoid Injection<br> | Drug: Aripiprazole, OPC-14597<br>* 5 monthly applications of 400 mg of aripiprazole IM depot, where the first application is in the gluteal or deltoid muscle followed by 4 monthly administrations to the deltoid muscle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs). | AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the investigator. A serious adverse event (SAE) was any untoward medical occurrence that resulted in death or was life threatening or required inpatient hospitalization or prolonged hospitalization. A treatment-emergent AE (TEAE) was defined as an AE that started after start of study medication or an AE that continued from baseline and that worsened, was serious, was study medication related, or resulted in death, discontinuation, interruption, or reduction of study medication. | AEs were recorded from the time the informed consent was signed until follow-up for 28 days after last | 
| Mean Visual Analog Scale (VAS) Score for Rating of Pain at the Injection Site. | Participants assessed the pain associated with injection of aripiprazole IM using the VAS instrument. This was done approximately 30 minutes pre-dose and 1 hour (±15 min) Post-dose on Days 1, 29, 57, 85 and 113. For the first injection, the pre-dose assessment was of the current injection site. For the injections 2 through 5, the pre-dose assessment was of the prior injection site. Investigator's Assessment of Most Recent Injection Site including pain, swelling, redness, and induration were reported in 4-point categorical scale (1 = absent, 2 = mild, 3 = moderate and 4 = severe) by first injection site at each injection. | Days 1 and 113 | 
| Mean Change From Baseline in Suicidal Ideation Intensity Total Score Via Columbia-suicide Severity Rating Scale (C-SSRS). | Suicidality was monitored throughout the trial using C-SSRS. The C-SSRS addresses the need for standardized classification of suicide reports to assess suicide risk. This scale consisted of Baseline evaluation that assessed the lifetime experience of the participant with suicidal events and suicidal ideation and a post baseline evaluation that focuses on suicidality since the last trial visit. The C-SSRS since last visit form were completed on Day 1 pre-dose and prior to dosing on Days 29, 57, 85, 113, 141/ Early Termination(ET) and prior to pharmacokinetics(PK) sampling on Days 8, 15, 22, 120, 127 and 134. The suicidal ideation intensity total score was the sum of suicidal ideation severity rating scores for frequency, duration, controllability, deterrents, and reasons for ideation. For each item, each participant got an intensity score from 0(none) to 5(worst). Therefore,the suicidal ideation intensity total score range from 0 to 25, with a score of 0 given for no suicidal ideation. | Baseline to Last Visit (Day 141) | 
| Mean Change From Baseline Measured by Extrapyramidal Symptoms (EPS) by Simpson-Angus Scale (SAS). | The SAS consisted of a list of 10 symptoms of Parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). The SAS Total Score was the sum of the scores for all 10 items. SAS total score can range from 10 to 50. Each item was rated on a 5-point scale, with a score of 1 =absence of symptoms and a score of 5 =severe condition. | Baseline to Week 20 | 
| Mean Change From Baseline Measured by EPS by Abnormal Involuntary Movement Scale (AIMS). | The AIMS assessment consisted of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7) were observed unobtrusively while the participant was at rest (e.g., in the waiting room), and the study physician would make global judgments on the participant's dyskinesia's (items 8 through 10). These items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Overall AIMS scores range from 0 to 42. | Baseline to Week 20 | 
| Mean Change From Baseline Measured by EPS by Barnes Akathisia Rating Scale (BARS). | The BARS consisted of 4 items related to akathisia: objective observation of akathisia by the study physician, subjective feelings of restlessness by the participant, participant distress due to akathisia, and global evaluation of akathisia. To complete this scale, participants were observed while they were seated and then stood for a minimum of 2 minutes in each position. Symptoms observed in other situations (e.g., while engaged in neutral conversation or engaged in activity on the ward) may also be rated. Subjective phenomena were to be elicited by direct questioning. The first 3 items were rated on a 4-point scale, with a score of 0 = absence of symptoms and a score of 3 = severe condition. The global clinical evaluation were made on a 6-point scale, (0=absent, 1=questionable, 2=mild, 3=moderate, 4=marked, 5=severe). | Baseline to Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS). | 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 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). | Baseline to Week 20 | 
| Mean Change From Baseline in PANSS Positive Sub-scale 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 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). | Baseline to Week 20 | 
| Mean Change From Baseline in PANSS Negative Sub-scale 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 (absence of symptoms) and a score of 7 (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: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). | Baseline to Week 20 | 
| Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score. | The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. | Baseline to Week 20 | 
| Clinical Global Impression-Improvement (CGI-I) Score. | The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition a baseline. Response choices include: 0 = not assessed; 1 =very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 =minimally worse; 6 = much worse; and 7 = very much worse. | Baseline to Week 20 | 
| Mean Change From Baseline in Total Score of Subject Well-being Under Neuroleptic Treatment-Short Form (SWN-S). | The participant's feeling of their own well-being was assessed using the 20 question SWN-S. The SWN-S was a validated self-report instrument that evaluated the participant's perception of 1 being while receiving antipsychotic medication. The questionnaire consisted of 20 items and 5 subscales (mental functioning, social integration, emotional regulation, physical functioning, self-control) whose items followed in random order. For items marked with a '+', response choices and scoring were as follows: not at all = 1, hardly at all = 2, a little = 3, somewhat = 4, much = 5, very much = 6. For items marked with a '-', the scoring was reversed; response choices and scoring were as follows: not at all = 6, hardly at all = 5, a little = 4, somewhat = 3, much = 2, very much = 1. The total score from the scale ranges from 20 (bad subjective experience) to 120 (perfect subjective experience). | Baseline to Week 20+ | 
| Mean Change From Baseline in Mental Functioning Score of SWN-S. | The participant's feeling of their own well-being was assessed using the 20 question SWN-S. The SWN-S was a validated self-report instrument that evaluated the participant's perception of 1 being while receiving antipsychotic medication. The questionnaire consisted of 20 items and 5 subscales (mental functioning, social integration, emotional regulation, physical functioning, self-control) whose items followed in random order. For items marked with a '+', response choices and scoring were as follows: not at all = 1, hardly at all = 2, a little = 3, somewhat = 4, much = 5, very much = 6. For items marked with a '-', the scoring was reversed; response choices and scoring were as follows: not at all = 6, hardly at all = 5, a little = 4, somewhat = 3, much = 2, very much = 1. SWN-S subscale score's each item was rated on a score of 0 (none) to 6 (severe), with higher scores indicating stronger subjective feelings of deficit. | Baseline to Week 20 | 
| Mean Change From Baseline in Self Control Score of SWN-S. | The participant's feeling of their own well-being was assessed using the 20 question SWN-S. The SWN-S was a validated self-report instrument that evaluated the participant's perception of 1 being while receiving antipsychotic medication. The questionnaire consisted of 20 items and 5 subscales (mental functioning, social integration, emotional regulation, physical functioning, self-control) whose items followed in random order. For items marked with a '+', response choices and scoring were as follows: not at all = 1, hardly at all = 2, a little = 3, somewhat = 4, much = 5, very much = 6. For items marked with a '-', the scoring was reversed; response choices and scoring were as follows: not at all = 6, hardly at all = 5, a little = 4, somewhat = 3, much = 2, very much = 1. SWN-S subscale score's each item was rated on a score of 0 (none) to 6 (severe), with higher scores indicating stronger subjective feelings of deficit. | Baseline to Week 20 | 
| Mean Change From Baseline in Physical Functioning Score of SWN-S. | The participant's feeling of their own well-being was assessed using the 20 question SWN-S. The SWN-S was a validated self-report instrument that evaluated the participant's perception of 1 being while receiving antipsychotic medication. The questionnaire consisted of 20 items and 5 subscales (mental functioning, social integration, emotional regulation, physical functioning, self-control) whose items followed in random order. For items marked with a '+', response choices and scoring were as follows: not at all = 1, hardly at all = 2, a little = 3, somewhat = 4, much = 5, very much = 6. For items marked with a '-', the scoring was reversed; response choices and scoring were as follows: not at all = 6, hardly at all = 5, a little = 4, somewhat = 3, much = 2, very much = 1. SWN-S subscale score's each item was rated on a score of 0 (none) to 6 (severe), with higher scores indicating stronger subjective feelings of deficit. | Baseline to Week 20 | 
| Mean Change From Baseline in Emotional Regulation Score of SWN-S. | The participant's feeling of their own well-being was assessed using the 20 question SWN-S. The SWN-S was a validated self-report instrument that evaluated the participant's perception of 1 being while receiving antipsychotic medication. The questionnaire consisted of 20 items and 5 subscales (mental functioning, social integration, emotional regulation, physical functioning, self-control) whose items followed in random order. For items marked with a '+', response choices and scoring were as follows: not at all = 1, hardly at all = 2, a little = 3, somewhat = 4, much = 5, very much = 6. For items marked with a '-', the scoring was reversed; response choices and scoring were as follows: not at all = 6, hardly at all = 5, a little = 4, somewhat = 3, much = 2, very much = 1. SWN-S subscale score's each item was rated on a score of 0 (none) to 6 (severe), with higher scores indicating stronger subjective feelings of deficit. | Baseline to Week 20 | 
| Mean Change From Baseline in Social Integration Score of SWN-S. | The participant's feeling of their own well-being was assessed using the 20 question SWN-S. The SWN-S was a validated self-report instrument that evaluated the participant's perception of 1 being while receiving antipsychotic medication. The questionnaire consisted of 20 items and 5 subscales (mental functioning, social integration, emotional regulation, physical functioning, self-control) whose items followed in random order. For items marked with a '+', response choices and scoring were as follows: not at all = 1, hardly at all = 2, a little = 3, somewhat = 4, much = 5, very much = 6. For items marked with a '-', the scoring was reversed; response choices and scoring were as follows: not at all = 6, hardly at all = 5, a little = 4, somewhat = 3, much = 2, very much = 1. SWN-S subscale score's each item was rated on a score of 0 (none) to 6 (severe), with higher scores indicating stronger subjective feelings of deficit. | Baseline to Week 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OPC-14597, Aripiprazole, Schizophrenia