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

Primary Purpose

Schizophrenia, Bipolar I Disorder

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Aripiprazole

About this trial

This is an interventional basic science trial for Schizophrenia

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Woodland International Research Group
Collaborative Neuroscience Network
Hassman Research Institute
Community Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Arm Label

Part A - Deltoid Site: Single Dose Group

Part A - Gluteal Site: Single Dose Group

Part A - Deltoid Site: Multiple Dose Group

Part A - Gluteal Site: Multiple Dose Group

Part B - Gluteal Site: Group 1 (X)

Part B - Gluteal Site: Group 1 (Y)

Part B - Gluteal Site: Group 2

Arm Description

Participants will receive a single dose of aripiprazole LAI.

Participants will receive five injections of aripiprazole LAI, administered at monthly intervals.

Participants will receive a single dose of aripiprazole LAI.

Outcomes

Primary Outcome Measures

Part A - Single Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole

Part B - Group 1: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole

Part B - Group 2: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole

Part A - Single Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

Part B - Group 1: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

Part B - Group 2: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

Part A - Single Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole

Part B - Group 1: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole

Part B - Group 2: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole

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

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

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

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

Part B - Group 1: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole

Part B - Group 2: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole

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

Part B - Group 1: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole

Part B - Group 2: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole

Part A - Single Dose Group: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole

Part B - Group 1: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole

Part B - Group 2: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole

Part A - Single Dose Group: Oral Clearance (CL/F) for Aripiprazole Only

Apparent clearance of the drug from plasma after extravascular administration (CL/F).

Part B - Group 1: Oral Clearance (CL/F) for Aripiprazole Only

Apparent clearance of the drug from plasma after extravascular administration (CL/F).

Part B - Group 2: Oral Clearance (CL/F) for Aripiprazole Only

Apparent clearance of the drug from plasma after extravascular administration (CL/F).

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.

Part A - Multiple Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

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.

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.

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.

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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.

Part A - Single Dose: Number of Participants with Markedly Abnormal Clinical Laboratory Results

Clinical Laboratory Monitoring includes serum chemistry, hematology and urinalysis.

Part A - Multiple Dose: Number of Participants with Markedly Abnormal Clinical Laboratory Results

Clinical Laboratory Monitoring includes serum chemistry, hematology and urinalysis.

Part B: Number of Participants with Markedly Abnormal Clinical Laboratory Results

Clinical Laboratory Monitoring includes serum chemistry, hematology and urinalysis.

Part A - Single Dose: Change from Baseline in Serum Prolactin

Part A - Multiple Dose: Change from Baseline in Serum Prolactin

Part B: Change from Baseline in Serum Prolactin

Part A - Single Dose: Number of Participants with Markedly Abnormal Physical Examination Results

Part A - Multiple Dose: Number of Participants with Markedly Abnormal Physical Examination Results

Part B: Number of Participants with Markedly Abnormal Physical Examination Results

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.

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.

Part B: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception

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.

Part A - Multiple Dose: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score

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.

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.

Part A - Multiple Dose: Number of Injection Site Related Adverse Events

Part B: Number of Injection Site Related Adverse Events

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.

Part A - Multiple Dose: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)

Part B: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)

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.

Part A - Multiple Dose: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score

Part B: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score

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.

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.

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.

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.

Part A - Multiple Dose: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWN-S) Score

Part B: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWNS) Score

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.

Part A - Multiple Dose: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score

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.

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.

Part A - Multiple Dose: Change from Baseline in Young Mania Rating Scale (YMRS) Score

Part B: Change from Baseline in Young Mania Rating Scale (YMRS) Score

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.

Part A - Multiple Dose: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score

Part B: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score

Full Information

NCT ID

NCT03854409

First Posted

February 12, 2019

Last Updated

August 31, 2020

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Collaborators

PRA Health Sciences, H. Lundbeck A/S

1. Study Identification

Unique Protocol Identification Number

NCT03854409

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Completed

Study Start Date

January 31, 2019 (Actual)

Primary Completion Date

April 5, 2019 (Actual)

Study Completion Date

February 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Collaborators

PRA Health Sciences, H. Lundbeck A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

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

Schizophrenia, Bipolar I Disorder

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

72 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A - Deltoid Site: Single Dose Group

Arm Type

Experimental

Arm Description

Participants will receive a single dose of aripiprazole LAI.

Arm Title

Part A - Gluteal Site: Single Dose Group

Arm Type

Experimental

Arm Description

Participants will receive a single dose of aripiprazole LAI.

Arm Title

Part A - Deltoid Site: Multiple Dose Group

Arm Type

Experimental

Arm Description

Participants will receive five injections of aripiprazole LAI, administered at monthly intervals.

Arm Title

Part A - Gluteal Site: Multiple Dose Group

Arm Type

Experimental

Arm Description

Participants will receive five injections of aripiprazole LAI, administered at monthly intervals.

Arm Title

Part B - Gluteal Site: Group 1 (X)

Arm Type

Experimental

Arm Description

Participants will receive a single dose of aripiprazole LAI.

Arm Title

Part B - Gluteal Site: Group 1 (Y)

Arm Type

Experimental

Arm Description

Participants will receive a single dose of aripiprazole LAI.

Arm Title

Part B - Gluteal Site: Group 2

Arm Type

Experimental

Arm Description

Participants will receive a single dose of aripiprazole LAI.

Intervention Type

Drug

Intervention Name(s)

Aripiprazole

Other Intervention Name(s)

(OPC-14597)

Intervention Description

Injection.

Primary Outcome Measure Information:

Title

Part A - Single Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 126

Title

Part B - Group 1: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 57

Title

Part B - Group 2: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 57

Title

Part A - Single Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 28

Title

Part B - Group 1: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 28

Title

Part B - Group 2: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 28

Title

Part A - Single Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 126

Title

Part B - Group 1: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 57

Title

Part B - Group 2: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 57

Title

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

Time Frame

Day 1 to Day 126

Title

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

Time Frame

Day 1 to Day 57

Title

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

Time Frame

Day 1 to Day 57

Title

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

Time Frame

Day 1 to Day 28

Title

Part B - Group 1: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 28

Title

Part B - Group 2: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 28

Title

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

Time Frame

Day 1 to Day 126

Title

Part B - Group 1: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 57

Title

Part B - Group 2: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 57

Title

Part A - Single Dose Group: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 126

Title

Part B - Group 1: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 57

Title

Part B - Group 2: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 1 to Day 57

Title

Part A - Single Dose Group: Oral Clearance (CL/F) for Aripiprazole Only

Description

Apparent clearance of the drug from plasma after extravascular administration (CL/F).

Time Frame

Day 1 to Day 126

Title

Part B - Group 1: Oral Clearance (CL/F) for Aripiprazole Only

Description

Apparent clearance of the drug from plasma after extravascular administration (CL/F).

Time Frame

Day 1 to Day 57

Title

Part B - Group 2: Oral Clearance (CL/F) for Aripiprazole Only

Description

Apparent clearance of the drug from plasma after extravascular administration (CL/F).

Time Frame

Day 1 to Day 57

Title

Part A - Multiple Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole (Following the Fifth Dose Only)

Description

Fifth dose will be administered on Day 113.

Time Frame

Day 113 to Day 169

Title

Part A - Multiple Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

Time Frame

Day 29, Day 57, Day 84, Day 113, Day 141 (All post-dose)

Title

Part A - Multiple Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole

Description

Participants will receive their 5th dose on Day 113.

Time Frame

Day 113 to Day 169

Title

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

Description

Participants will receive their 5th dose on Day 113.

Time Frame

Day 113 to Day 169

Title

Part A - Multiple Dose Group: Terminal Phase Elimination Half-life (T1/2) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole

Description

Participants will receive their 5th dose on Day 113.

Time Frame

Day 113 to Day 169

Title

Part A - Multiple Dose Group: Oral Clearance (CL/F) (Following the Fifth Dose Only; for Aripiprazole Only)

Description

Participants will receive their 5th dose on Day 113.

Time Frame

Day 113 to Day 169

Title

Part A - Multiple Dose Group: Ratio of Dehydro-Aripiprazole to Aripiprazole C28 and AUC0-28 (Following the Fifth Dose Only)

Description

Participants will receive their 5th dose on Day 113.

Time Frame

Day 113 (following fifth dose) to Day 141

Secondary Outcome Measure Information:

Title

Part A - Single Dose: Number of Participants with an Adverse Event (AE)

Description

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.

Time Frame

Day 1 to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Number of Participants with an Adverse Event (AE)

Description

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.

Time Frame

Day 1 to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Number of Participants with an Adverse Event (AE)

Description

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.

Time Frame

Day 1 to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Number of Participants with Markedly Abnormal Vital Sign Measurements

Description

Vital signs will be obtained prior to PK blood draws. Vital signs will include systolic and diastolic blood pressure, heart rate, and body temperature.

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Number of Participants with Markedly Abnormal Vital Sign Measurements

Description

Vital signs will be obtained prior to PK blood draws. Vital signs will include systolic and diastolic blood pressure, heart rate, and body temperature.

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Number of Participants with Markedly Abnormal Vital Sign Measurements

Description

Vital signs will be obtained prior to PK blood draws. Vital signs will include systolic and diastolic blood pressure, heart rate, and body temperature.

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results

Description

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.

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results

Description

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.

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results

Description

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.

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Number of Participants with Markedly Abnormal Clinical Laboratory Results

Description

Clinical Laboratory Monitoring includes serum chemistry, hematology and urinalysis.

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Number of Participants with Markedly Abnormal Clinical Laboratory Results

Description

Clinical Laboratory Monitoring includes serum chemistry, hematology and urinalysis.

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Number of Participants with Markedly Abnormal Clinical Laboratory Results

Description

Clinical Laboratory Monitoring includes serum chemistry, hematology and urinalysis.

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Change from Baseline in Serum Prolactin

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Change from Baseline in Serum Prolactin

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Change from Baseline in Serum Prolactin

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Number of Participants with Markedly Abnormal Physical Examination Results

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Number of Participants with Markedly Abnormal Physical Examination Results

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Number of Participants with Markedly Abnormal Physical Examination Results

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception

Description

Time Frame

Day 1 immediately post-dose, 1 hour post-dose (+/- 15 minutes), Day 14 and Day 29

Title

Part A - Multiple Dose: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception

Description

Time Frame

1-hour post-dose Day 1, Day 29, Day 57, Day 85, Day 113

Title

Part B: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception

Description

Time Frame

Day 1 immediately post-dose, 1 hour post-dose (+/- 15 minutes), Day 14 and Day 29

Title

Part A - Single Dose: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score

Description

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.

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Number of Injection Site Related Adverse Events

Description

Time Frame

End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Number of Injection Site Related Adverse Events

Description

Time Frame

End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Number of Injection Site Related Adverse Events

Description

Time Frame

End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)

Description

Time Frame

Day 1 (predose) to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)

Description

Time Frame

Day 1 (predose) to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)

Description

Time Frame

Day 1 (predose) to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score

Description

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.

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score

Description

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.

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score

Description

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.

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWN-S) Score

Description

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWN-S) Score

Description

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWNS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score

Description

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.

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Change from Baseline in Young Mania Rating Scale (YMRS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Change from Baseline in Young Mania Rating Scale (YMRS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Change from Baseline in Young Mania Rating Scale (YMRS) Score

Description

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

Title

Part A - Single Dose: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score

Description

Time Frame

Baseline to End of Trial (Maximum 126 Days from First Dose)

Title

Part A - Multiple Dose: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score

Description

Time Frame

Baseline to End of Trial (Maximum 169 Days from First Dose)

Title

Part B: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score

Description

Time Frame

Baseline to End of Trial (Maximum 57 Days from First Dose)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Facility Information:

Facility Name

Woodland International Research Group

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72211

Country

United States

Facility Name

Collaborative Neuroscience Network

City

Garden Grove

State/Province

California

ZIP/Postal Code

92845

Country

United States

Facility Name

Hassman Research Institute

City

Berlin

State/Province

New Jersey

ZIP/Postal Code

08009

Country

United States

Facility Name

Community Clinical Research

City

Austin

State/Province

Texas

ZIP/Postal Code

78754

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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 URL

https://clinical-trials.otsuka.com

Learn more about this trial

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

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