A Trial of Single- and Multiple-doses of Aripiprazole in Adult Subjects With Schizophrenia or Bipolar I Disorder

An Open-label, Single- and Multiple-dose, Pharmacokinetic, Safety, and Tolerability Trial of Aripiprazole Long-acting Injectable Administered in the Deltoid or Gluteal Muscle in Adult Subjects With Schizophrenia or Bipolar I Disorder

The primary objective of this trial is to evaluate the pharmacokinetics (PK) of aripiprazole long-acting injectable (LAI) (420 mg) following deltoid or gluteal muscle administration in adult subjects with schizophrenia or bipolar I disorder.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Bipolar I Disorder
• Intervention / Treatment: Drug: Aripiprazole

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
  • California
    • Garden Grove, California, United States, 92845
      • Collaborative NeuroScience Network
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects between 18 and 64 years of age, inclusive.
• Body mass index of 18 to 35 kg/m2, inclusive.
• A current diagnosis of schizophrenia or a current diagnosis of bipolar I disorder as defined by DSM-5 criteria.
• Prior history of tolerating aripiprazole per investigator's judgment.

Exclusion Criteria:

• Subjects who have met DSM-5 criteria for substance dependence within the past 180 days
• Use of any psychotropic medications other than their current non-aripiprazole antipsychotic or mood stabilizer(s) medication or subjects who use more than one antipsychotic or mood stabilizer(s) medication at screening.
• Subjects may not receive varenicline beyond screening.
• Use of any prescription medication not specifically approved by the medical monitor.
• Females who are pregnant or lactating. A negative serum pregnancy test must be confirmed prior to the first dose of IMP for all female subjects.
• Subjects who had participated in any clinical trial involving a psychotropic medication within 1 month prior to enrollment; subjects who had participated in a previous aripiprazole LAI trial within the last 1 year (ie, enrolled but did not receive aripiprazole LAI); or who had previously enrolled and received IMP in an aripiprazole LAI clinical trial.
• Any major surgery within 30 days prior to enrollment or scheduled/elective surgery during the trial.
• Subjects currently in an acute relapse of schizophrenia.
• Subjects with a current DSM-5 diagnosis other than schizophrenia or bipolar I disorder
• Electroconvulsive therapy must not be conducted within 2 months prior to administration of the IMP
• Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia as assessed by the investigator.
• History of or current hepatitis or acquired immunodeficiency syndrome or carriers of HBsAg, anti-HCV, and/or HIV antibodies.
• History of any significant drug allergy or known or suspected hypersensitivity, in particular to aripiprazole or other quinolinones.
• Subjects deemed intolerant of receiving injections.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A - Deltoid Site: Single Dose Group; Participants will receive a single dose of aripiprazole LAI.	Drug: Aripiprazole; Injection.; Other Names: (OPC-14597)
Experimental: Part A - Gluteal Site: Single Dose Group; Participants will receive a single dose of aripiprazole LAI.	Drug: Aripiprazole; Injection.; Other Names: (OPC-14597)
Experimental: Part A - Deltoid Site: Multiple Dose Group; Participants will receive five injections of aripiprazole LAI, administered at monthly intervals.	Drug: Aripiprazole; Injection.; Other Names: (OPC-14597)
Experimental: Part A - Gluteal Site: Multiple Dose Group; Participants will receive five injections of aripiprazole LAI, administered at monthly intervals.	Drug: Aripiprazole; Injection.; Other Names: (OPC-14597)
Experimental: Part B - Gluteal Site: Group 1 (X); Participants will receive a single dose of aripiprazole LAI.	Drug: Aripiprazole; Injection.; Other Names: (OPC-14597)
Experimental: Part B - Gluteal Site: Group 1 (Y); Participants will receive a single dose of aripiprazole LAI.	Drug: Aripiprazole; Injection.; Other Names: (OPC-14597)
Experimental: Part B - Gluteal Site: Group 2; Participants will receive a single dose of aripiprazole LAI.	Drug: Aripiprazole; Injection.; Other Names: (OPC-14597)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A - Single Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 126
Part B - Group 1: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 57
Part B - Group 2: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 57
Part A - Single Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole		Day 28
Part B - Group 1: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole		Day 28
Part B - Group 2: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole		Day 28
Part A - Single Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 126
Part B - Group 1: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 57
Part B - Group 2: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 57
Part A - Single Dose Group: Area Under the Concentration-Time Curve from time Zero to Time t (the Last Observable Concentration; AUCt) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 126
Part B - Group 1: Area Under the Concentration-Time Curve from time Zero to Time t (the Last Observable Concentration; AUCt) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 57
Part B - Group 2: Area Under the Concentration-Time Curve from time Zero to Time t (the Last Observable Concentration; AUCt) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 57
Part A - Single Dose Group: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 28
Part B - Group 1: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 28
Part B - Group 2: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 28
Part A - Single Dose Group: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 126
Part B - Group 1: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 57
Part B - Group 2: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 57
Part A - Single Dose Group: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 126
Part B - Group 1: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 57
Part B - Group 2: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole		Day 1 to Day 57
Part A - Single Dose Group: Oral Clearance (CL/F) for Aripiprazole Only	Apparent clearance of the drug from plasma after extravascular administration (CL/F).	Day 1 to Day 126
Part B - Group 1: Oral Clearance (CL/F) for Aripiprazole Only	Apparent clearance of the drug from plasma after extravascular administration (CL/F).	Day 1 to Day 57
Part B - Group 2: Oral Clearance (CL/F) for Aripiprazole Only	Apparent clearance of the drug from plasma after extravascular administration (CL/F).	Day 1 to Day 57
Part A - Multiple Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole (Following the Fifth Dose Only)	Fifth dose will be administered on Day 113.	Day 113 to Day 169
Part A - Multiple Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole		Day 29, Day 57, Day 84, Day 113, Day 141 (All post-dose)
Part A - Multiple Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole	Participants will receive their 5th dose on Day 113.	Day 113 to Day 169
Part A - Multiple Dose Group: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole	Participants will receive their 5th dose on Day 113.	Day 113 to Day 169
Part A - Multiple Dose Group: Terminal Phase Elimination Half-life (T1/2) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole	Participants will receive their 5th dose on Day 113.	Day 113 to Day 169
Part A - Multiple Dose Group: Oral Clearance (CL/F) (Following the Fifth Dose Only; for Aripiprazole Only)	Participants will receive their 5th dose on Day 113.	Day 113 to Day 169
Part A - Multiple Dose Group: Ratio of Dehydro-Aripiprazole to Aripiprazole C28 and AUC0-28 (Following the Fifth Dose Only)	Participants will receive their 5th dose on Day 113.	Day 113 (following fifth dose) to Day 141

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A - Single Dose: Number of Participants with an Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Day 1 to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Number of Participants with an Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Day 1 to End of Trial (Maximum 169 Days from First Dose)
Part B: Number of Participants with an Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Day 1 to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Number of Participants with Markedly Abnormal Vital Sign Measurements	Vital signs will be obtained prior to PK blood draws. Vital signs will include systolic and diastolic blood pressure, heart rate, and body temperature.	Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Number of Participants with Markedly Abnormal Vital Sign Measurements	Vital signs will be obtained prior to PK blood draws. Vital signs will include systolic and diastolic blood pressure, heart rate, and body temperature.	Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Number of Participants with Markedly Abnormal Vital Sign Measurements	Vital signs will be obtained prior to PK blood draws. Vital signs will include systolic and diastolic blood pressure, heart rate, and body temperature.	Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results	Standard 12-lead ECGs will be collected in triplicate (5 minutes apart). The ECGs will be collected prior to PK blood draws and after vital signs at the nominal time points, where applicable.	Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results	Standard 12-lead ECGs will be collected in triplicate (5 minutes apart). The ECGs will be collected prior to PK blood draws and after vital signs at the nominal time points, where applicable.	Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results	Standard 12-lead ECGs will be collected in triplicate (5 minutes apart). The ECGs will be collected prior to PK blood draws and after vital signs at the nominal time points, where applicable.	Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Number of Participants with Markedly Abnormal Clinical Laboratory Results	Clinical Laboratory Monitoring includes serum chemistry, hematology and urinalysis.	Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Number of Participants with Markedly Abnormal Clinical Laboratory Results	Clinical Laboratory Monitoring includes serum chemistry, hematology and urinalysis.	Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Number of Participants with Markedly Abnormal Clinical Laboratory Results	Clinical Laboratory Monitoring includes serum chemistry, hematology and urinalysis.	Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Change from Baseline in Serum Prolactin		Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Change from Baseline in Serum Prolactin		Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Change from Baseline in Serum Prolactin		Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Number of Participants with Markedly Abnormal Physical Examination Results		Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Number of Participants with Markedly Abnormal Physical Examination Results		Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Number of Participants with Markedly Abnormal Physical Examination Results		Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception	VAS scores at Day 1 immediately post-dose, 1 hour post-dose (+/- 15 minutes), Day 14 and Day 29. The VAS is a test to assess injection site pain. Participants will be asked to give a score between 0-10 to rate pain, with 0 being no pain and 10 being worst possible pain.	Day 1 immediately post-dose, 1 hour post-dose (+/- 15 minutes), Day 14 and Day 29
Part A - Multiple Dose: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception	VAS scores at 1-hour post-dose on Day 1, Day 29, Day 57, Day 85, Day 113. The VAS is a test to assess injection site pain. Participants will be asked to give a score between 0-10 to rate pain, with 0 being no pain and 10 being worst possible pain.	1-hour post-dose Day 1, Day 29, Day 57, Day 85, Day 113
Part B: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception	VAS scores at Day 1 immediately post-dose, 1 hour post-dose (+/- 15 minutes), Day 14 and Day 29. The VAS is a test to assess injection site pain. Participants will be asked to give a score between 0-10 to rate pain, with 0 being no pain and 10 being worst possible pain.	Day 1 immediately post-dose, 1 hour post-dose (+/- 15 minutes), Day 14 and Day 29
Part A - Single Dose: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score	Suicidality will be monitored throughout the trial using the C-SSRS (Columbia-Suicide Severity Rating Scale). This scale consists of a baseline evaluation that assesses the lifetime experience of the subject with suicide events and suicidal ideation and a post-baseline evaluation that focuses on suicidality since the last assessment.The Baseline/Screening Version and the Since Last Visit version of the C-SSRS will be completed by trained trial site staff at each visit. A numerical score will correspond to one of ten categories relating to suicidal ideation and suicidal behavior. A higher score indicates a higher risk of suicidal behavior, but an answer of 'yes' to any question indicates some risk.	Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score	Suicidality will be monitored throughout the trial using the C-SSRS (Columbia-Suicide Severity Rating Scale). This scale consists of a baseline evaluation that assesses the lifetime experience of the subject with suicide events and suicidal ideation and a post-baseline evaluation that focuses on suicidality since the last assessment.The Baseline/Screening Version and the Since Last Visit version of the C-SSRS will be completed by trained trial site staff at each visit. A numerical score will correspond to one of ten categories relating to suicidal ideation and suicidal behavior. A higher score indicates a higher risk of suicidal behavior, but an answer of 'yes' to any question indicates some risk.	Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score	Suicidality will be monitored throughout the trial using the C-SSRS (Columbia-Suicide Severity Rating Scale). This scale consists of a baseline evaluation that assesses the lifetime experience of the subject with suicide events and suicidal ideation and a post-baseline evaluation that focuses on suicidality since the last assessment.The Baseline/ Screening Version and the Since Last Visit version of the C-SSRS will be completed by trained trial site staff at each visit. A numerical score will correspond to one of ten categories relating to suicidal ideation and suicidal behavior. A higher score indicates a higher risk of suicidal behavior, but an answer of 'yes' to any question indicates some risk.	Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Number of Injection Site Related Adverse Events	An AE is defined as any untoward medical occurrence in a clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.The injection site will be monitored by the investigator to assess the safety and tolerability of the drug.	End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Number of Injection Site Related Adverse Events	An AE is defined as any untoward medical occurrence in a clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.The injection site will be monitored by the investigator to assess the safety and tolerability of the drug.	End of Trial (Maximum 169 Days from First Dose)
Part B: Number of Injection Site Related Adverse Events	An AE is defined as any untoward medical occurrence in a clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.The injection site will be monitored by the investigator to assess the safety and tolerability of the drug.	End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)	EPS will be assessed using Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS) and Barnes Akathisia Rating Scale (BARS). The SAS consists of a list of 10 symptoms of Parkinsonism. Each item will be rated on a 5-point scale, with a score of 1 representing absence of symptoms and a score of 5 representing a severe condition. The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Each item will be rated on a 5-point scale, with a score of 0 representing absence of symptoms, and a score of 4 indicating a severe condition. The BARS consist of 4 items related to akathisia. The first 3 items will be rated on a 4-point scale, with a score of 0 representing absence of symptoms and a score of 3 representing a severe condition. The global clinical evaluation will be made on a 6-point scale, with 0 representing absence of symptoms and 5 representing severe akathisia.	Day 1 (predose) to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)	EPS will be assessed using Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS) and Barnes Akathisia Rating Scale (BARS). The SAS consists of a list of 10 symptoms of Parkinsonism. Each item will be rated on a 5-point scale, with a score of 1 representing absence of symptoms and a score of 5 representing a severe condition. The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Each item will be rated on a 5-point scale, with a score of 0 representing absence of symptoms, and a score of 4 indicating a severe condition. The BARS consist of 4 items related to akathisia. The first 3 items will be rated on a 4-point scale, with a score of 0 representing absence of symptoms and a score of 3 representing a severe condition. The global clinical evaluation will be made on a 6-point scale, with 0 representing absence of symptoms and 5 representing severe akathisia.	Day 1 (predose) to End of Trial (Maximum 169 Days from First Dose)
Part B: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)	EPS will be assessed using Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS) and Barnes Akathisia Rating Scale (BARS). The SAS consists of a list of 10 symptoms of Parkinsonism. Each item will be rated on a 5-point scale, with a score of 1 representing absence of symptoms and a score of 5 representing a severe condition. The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Each item will be rated on a 5-point scale, with a score of 0 representing absence of symptoms, and a score of 4 indicating a severe condition. The BARS consist of 4 items related to akathisia. The first 3 items will be rated on a 4-point scale, with a score of 0 representing absence of symptoms and a score of 3 representing a severe condition. The global clinical evaluation will be made on a 6-point scale, with 0 representing absence of symptoms and 5 representing severe akathisia.	Day 1 (predose) to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score	The PANSS will be administered using the Structured Clinical Interview-PANSS. The PANSS consists of 3 subscales containing a total of 30 symptom constructs.13 For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. This analysis will include participants with schizophrenia only.	Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score	The PANSS will be administered using the Structured Clinical Interview-PANSS. The PANSS consists of 3 subscales containing a total of 30 symptom constructs.13 For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. This analysis will include participants with schizophrenia only.	Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score	The PANSS will be administered using the Structured Clinical Interview-PANSS. The PANSS consists of 3 subscales containing a total of 30 symptom constructs.13 For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. This analysis will include participants with schizophrenia only.	Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score	The CGI-S Scale will be used to rate the severity of illness for each participant. The scale is a 7-point likert scale, where 1 indicates no illness and 7 indicates extremely ill.	Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score	The CGI-S Scale will be used to rate the severity of illness for each participant. The scale is a 7-point likert scale, where 1 indicates no illness and 7 indicates extremely ill.	Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score	The CGI-S Scale will be used to rate the severity of illness for each participant. The scale is a 7-point likert scale, where 1 indicates no illness and 7 indicates extremely ill.	Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWN-S) Score	The subject's feeling of their own well-being will be assessed using the 20 question SWN-S. The questionnaire consists of 20 items and 5 subscales (mental functioning, social integration, emotional regulation, physical functioning, self-control) whose items follow in random order. For items marked with a '+', response choices and scoring are 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 is reversed; response choices and scoring are as follows: not at all = 6, hardly at all = 5, a little = 4, somewhat = 3, much = 2, very much = 1.	Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWN-S) Score	The subject's feeling of their own well-being will be assessed using the 20 question SWN-S. The questionnaire consists of 20 items and 5 subscales (mental functioning, social integration, emotional regulation, physical functioning, self-control) whose items follow in random order. For items marked with a '+', response choices and scoring are 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 is reversed; response choices and scoring are as follows: not at all = 6, hardly at all = 5, a little = 4, somewhat = 3, much = 2, very much = 1.	Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWNS) Score	The subject's feeling of their own well-being will be assessed using the 20 question SWN-S. The questionnaire consists of 20 items and 5 subscales (mental functioning, social integration, emotional regulation, physical functioning, self-control) whose items follow in random order. For items marked with a '+', response choices and scoring are 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 is reversed; response choices and scoring are as follows: not at all = 6, hardly at all = 5, a little = 4, somewhat = 3, much = 2, very much = 1.	Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score	The MADRS will be utilized as the primary assessment of a subject's level of depressive symptoms and must be administered using a structured interview guide. This scale consists of 10 items each with 7 defined grades of severity.This analysis will include participants with bipolar only.	Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score	The MADRS will be utilized as the primary assessment of a subject's level of depressive symptoms and must be administered using a structured interview guide. This scale consists of 10 items each with 7 defined grades of severity.This analysis will include participants with bipolar only.	Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score	The MADRS will be utilized as the primary assessment of a subject's level of depressive symptoms and must be administered using a structured interview guide. This scale consists of 10 items each with 7 defined grades of severity. This analysis will include participants with bipolar only.	Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Change from Baseline in Young Mania Rating Scale (YMRS) Score	The YMRS consists of 11 items assessing the core symptoms of mania and is based on the subject's subjective report of his or her clinical condition. Each item has 5 defined categories of severity with 4 items graded on a 0 to 8 scale (irritability, speech, content, and disruptive-aggressive behavior) and 7 items graded on a 0 to 4 scale. This analysis will include participants with bipolar only.	Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Change from Baseline in Young Mania Rating Scale (YMRS) Score	The YMRS consists of 11 items assessing the core symptoms of mania and is based on the subject's subjective report of his or her clinical condition. Each item has 5 defined categories of severity with 4 items graded on a 0 to 8 scale (irritability, speech, content, and disruptive-aggressive behavior) and 7 items graded on a 0 to 4 scale. This analysis will include participants with bipolar only.	Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Change from Baseline in Young Mania Rating Scale (YMRS) Score	The YMRS consists of 11 items assessing the core symptoms of mania and is based on the subject's subjective report of his or her clinical condition. Each item has 5 defined categories of severity with 4 items graded on a 0 to 8 scale (irritability, speech, content, and disruptive-aggressive behavior) and 7 items graded on a 0 to 4 scale. This analysis will include participants with bipolar only.	Baseline to End of Trial (Maximum 57 Days from First Dose)
Part A - Single Dose: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score	Severity of illness will be measured using the CGI-BP score. To assess CGI-S, the investigator will answer the following question: "Considering your total clinical experience with this particular population, how mentally ill is the subject at this time?" Response choices include: 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 subjects. This analysis will include participants with bipolar only.	Baseline to End of Trial (Maximum 126 Days from First Dose)
Part A - Multiple Dose: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score	Severity of illness will be measured using the CGI-BP score. To assess CGI-S, the investigator will answer the following question: "Considering your total clinical experience with this particular population, how mentally ill is the subject at this time?" Response choices include: 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 subjects. This analysis will include participants with bipolar only.	Baseline to End of Trial (Maximum 169 Days from First Dose)
Part B: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score	Severity of illness will be measured using the CGI-BP score. To assess CGI-S, the investigator will answer the following question: "Considering your total clinical experience with this particular population, how mentally ill is the subject at this time?" Response choices include: 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 subjects. This analysis will include participants with bipolar only.	Baseline to End of Trial (Maximum 57 Days from First Dose)

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: H. Lundbeck A/S; PRA Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2019
• Primary Completion (Actual): April 5, 2019
• Study Completion (Actual): February 20, 2020

Study Registration Dates

• First Submitted: February 12, 2019
• First Submitted That Met QC Criteria: February 22, 2019
• First Posted (Actual): February 26, 2019

Study Record Updates

• Last Update Posted (Actual): September 2, 2020
• Last Update Submitted That Met QC Criteria: August 31, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: 031-201-00279

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No