History of Changes for Study: NCT04030143

A Trial of Multiple-doses of Aripiprazole in Adults With Schizophrenia or Bipolar 1 Disorder

A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.

Study Record Versions

Version	Submitted Date	Changes
1	July 19, 2019	None (earliest Version on record)
2	August 21, 2019	Recruitment Status, Contacts/Locations, Study Status and Oversight
3	September 20, 2019	Contacts/Locations and Study Status
4	December 5, 2019	Recruitment Status, Study Status, Contacts/Locations and Study Design
5	April 17, 2020	Study Status
6	August 6, 2020	Recruitment Status and Study Status
7	August 31, 2020	IPDSharing and Study Status
8	June 8, 2021	Study Design and Study Status
9	June 16, 2021	Study Status
10	September 22, 2023	Quality Control Review has not concluded Returned: October 17, 2023 Outcome Measures, Study Status, Arms and Interventions, Document Section, Adverse Events, Baseline Characteristics, Participant Flow, Eligibility, Study Description, Oversight and Sponsor/Collaborators
11	October 27, 2023	Study Status, Outcome Measures and More Information

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	031-201-00181
Brief Title:	A Trial of Multiple-doses of Aripiprazole in Adults With Schizophrenia or Bipolar 1 Disorder
Official Title:	A Phase 1b, Open-label, Multiple-dose, Randomized, Parallel-arm, Safety, Tolerability, and Pharmacokinetic Trial of Aripiprazole Intramuscular Depot Administered in the Gluteal Muscle in Adult Subjects With Schizophrenia or Bipolar I Disorder
Secondary IDs:

Study Status


Record Verification:	July 2019
Overall Status:	Not yet recruiting
Study Start:	July 31, 2019
Primary Completion:	April 24, 2021 [Anticipated]
Study Completion:	April 24, 2021 [Anticipated]

First Submitted:	July 19, 2019
First Submitted that Met QC Criteria:	July 19, 2019
First Posted:	July 23, 2019 [Actual]

Last Update Submitted that Met QC Criteria:	July 19, 2019
Last Update Posted:	July 23, 2019 [Actual]

Sponsor/Collaborators


Sponsor:	Otsuka Pharmaceutical Development & Commercialization, Inc.
Responsible Party:	Sponsor
Collaborators:	PRA Health Sciences

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:

Study Description

Brief Summary:

The purpose of this trial is to determine the safety and tolerability of multiple-dose administrations of aripiprazole in adult participants with schizophrenia or bipolar I disorder. To establish the similarity of aripiprazole concentrations following the final administration of aripiprazole into the gluteal muscle site, and to establish the similarity of aripiprazole exposure following the final administration of aripiprazole into the gluteal muscle site.

Detailed Description:

Conditions


Conditions:	Schizophrenia Bipolar I Disorder
Keywords:	Aripiprazole Aripiprazole Intramuscular Depot Gluteal Muscle Long Acting Injection

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Randomized
Enrollment:	258 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Aripiprazole 2M LAI 2 Months (2M) Long-acting injection (LAI). Participants will receive a total of 4 injections of aripiprazole 2M LAI, administered every 56 days (+/- 2 days) from Day 1. Participants will continue to take their current oral antipsychotic or be given 10 to 20 mg oral aripiprazole for 7 days after the first administration.	Drug: Aripiprazole Aripiprazole long acting injection.
Active Comparator: Aripiprazole 1M depot injection 1 Month (1M) depot injection. Participants will receive a total of 8 injections of aripiprazole 1M depot, administered every 28 days (+/- 2 days) from Day 1. Participants will continue to take their current oral antipsychotic or be given 10 to 20 mg oral aripiprazole for 14 days after the first administration.	Drug: Aripiprazole Aripiprazole depot injection

Outcome Measures


Primary Outcome Measures:
1.	Number of Participants Reporting One of More Treatment-Emergent Adverse Event (TEAE) [ Time Frame: Baseline to Day 225 ] An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical trial where the participant is administered a medical product; it does not necessarily have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
2.	Number of Participants With a Markedly Abnormal Vital Signs Measurement [ Time Frame: Baseline to Day 225 ] Vital signs will include systolic and diastolic blood pressure, heart rate, and body temperature.
3.	Number of Participants With a Markedly Abnormal Electrocardiogram (ECG) Result [ Time Frame: Baseline to Day 225 ] The number of participants with any markedly abnormal electrocardiogram (ECG) collected throughout study
4.	Number of Participants With a Markedly Abnormal Clinical Laboratory Assessments [ Time Frame: Baseline to Day 225 ] The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.
5.	Number of Participants With a Markedly Abnormal Physical Examinations [ Time Frame: Baseline to Day 225 ] The number of participants with any markedly abnormal physical examination results collected throughout study
6.	Mean Change From Baseline in Simpson-Angus Scale Neurologic Rating Scale (SAS) [ Time Frame: Baseline to Day 225 ] To assess the extrapyramidal symptoms. The SAS consists 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). 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 cumulative score will range from 10 to 50.
7.	Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: Baseline to Day 225 ] To assess the extrapyramidal symptoms. The AIMS assessment consists 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) will be observed unobtrusively while the participant is at rest (eg, in the waiting room), and the investigators will also make global judgments on the participants dyskinesias (items 8 through 10). Each item will be rated on a 5-point scale, with a score of 0 representing absence of symptoms (for item 10, no awareness), and a score of 4 indicating a severe condition (for item 10, aware/severe distress). The cumulative score will range from 0 to 40.
8.	Mean Change From Baseline in Barnes Akathisia Rating Score (BARS) [ Time Frame: Baseline and Day 225 ] To assess the extrapyramidal symptoms. The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the participant, participant distress due to akathisia, and global evaluation of 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 a score of 5 representing severe akathisia.
9.	Mean Change From Baseline in Visual Analog Scale (VAS) Pain Perception Scores After The Last Dose [ Time Frame: 2M LAI: Baseline to Day 169; 1M depot injection: Baseline to Day 197 ] Participants will assess the perceived pain at the injection site associated with the injection of IMP using a visual analog scale (VAS). Participants randomized to 2M LAI will receive the last dose on Day 169, while participants randomized to 1M depot injection will receive the last dose on Day 197.
10.	Mean Change From Baseline in Investigators Assessment of The Injection Site Score After The Last Dose [ Time Frame: 2M LAI: Baseline to Day 169; 1M depot injection: Baseline to Day 197 ] The investigators or designees will assess the injection site. Participants randomized to 2M LAI will receive the last dose on Day 169, while participants randomized to 1M depot injection will receive the last dose on Day 197.
11.	Mean Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline to Day 225 ] Suicidality will be monitored during the trial using the C-SSRS. The scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicide events and suicidal ideation and a post baseline evaluation that focuses on suicidality since the last assessment.
12.	Plasma Concentration of Aripiprazole on Day 225 [ Time Frame: Day 225 ]
13.	Area Under the Plasma Concentration-Time Curve From Time 0 to 28 Days (AUC0-28) Post 7th and 8th Dose of Aripiprazole (1M depot injection) [ Time Frame: 0-12 hours post dose on Days 169 and 197, and on Days 170, 171, 173, 176, 178, 181, 183, 186, 190, 198, 199, 201, 204, 206, 209, 211, 214, 218 and 225 ] Participants randomized to 1M depot injection will receive the 7th and 8th dose on Days 169 and 197 respectively.
14.	Area Under the Plasma Concentration-Time Curve From Time 0 to 56 Days (AUC0-56) Post Last Dose of Aripiprazole (2M LAI) [ Time Frame: 0-12 hours post dose on Day 169, and on Days 170, 171, 173, 176, 178, 181, 183, 186, 190, 197, 204, 211, 218 and Day 225 ] Participants randomized to 2M LAI will receive the last dose on Day 169.
Secondary Outcome Measures:
1.	Maximum Observed Plasma Concentration (Cmax) of Aripiprazole [ Time Frame: 2M LAI: 0-12 hours post dose on Day 1 and 169; 1M depot injection: 0-12 hours on Day 1, 169 and 197 ] Cmax will be measured after the 1st and 4th dose of aripiprazole 2M LAI and after the 1st, 7th and 8th dose of aripiprazole 1M depot injection.
2.	Time to Reach the Maximum Plasma Concentration (Tmax) of Aripiprazole [ Time Frame: 2M LAI: 0-12 hours post dose on Day 1 and 169; 1M depot injection: 0-12 hours on Day 1, 169 and 197 ] Tmax will be measured after the 1st and 4th dose of aripiprazole 2M LAI and after the 1st, 7th and 8th dose of aripiprazole 1M depot injection.
3.	Area Under the Plasma Concentration-Time Curve From Time 0 to 28 Days (AUC0-28) Post First Dose of Aripiprazole (1M depot injection) [ Time Frame: 0-12 hours post first dose on Day 1, and Days 2, 3, 5, 8, 10, 13, 15, 18, 22, and 29 ]
4.	Area Under the Plasma Concentration-Time Curve From Time 0 to 56 Days (AUC0-56) Post First Dose of Aripiprazole (2M LAI) [ Time Frame: 0-12 hours post first dose on Day 1, and Days 2, 3, 5, 8, 10, 13, 15, 18, 22, 29, 36, 43, 50 and 57 ]
5.	Plasma Concentration of Aripiprazole 28 Days (C28) Post First Dose (1M depot injection) [ Time Frame: Day 29 ]
6.	Plasma Concentration of Aripiprazole 56 Days (C56) Post First Dose (2M LAI) [ Time Frame: Day 57 ]
7.	Area Under the Plasma Concentration-Time Curve From Time 0 to 28 Days (AUC0-28) Post Last Dose for Aripiprazole (2M LAI only) [ Time Frame: 0-12 hours post last dose on Day 169, and on Days 170, 171, 173, 176, 178, 181, 183, 186, 190, and 197 ]
8.	Plasma Concentration of Aripiprazole 28 to 56 Days (C28) Post Last Dose (2M LAI only) [ Time Frame: Day 197 to 225 ] Participants receiving 2M LAI will receive the last dose on Day 169.
9.	Peak-to-Trough Percent Fluctuation (PTF%) After the Last Dose of Aripiprazole [ Time Frame: 2M LAI: 0-12 hours post dose on Day 169, and at multiple time points from Day 170 to Day 255; 1M depot injection: 0-12 hours post dose on Day 197 and at multiple timepoints from Day 198 to 225 ]
10.	Plasma Concentration of Aripiprazole 14 Days (C14) Post First Dose (1M depot injection) [ Time Frame: Day 15 ]
11.	Plasma Concentration of Aripiprazole 7 Days (C7) Post First Dose (2M LAI) [ Time Frame: Day 8 ]
12.	Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) [ Time Frame: Baseline to Day 225 ] The PANSS consists of 3 subscales containing a total of 30 symptoms constructs developed to asses both the positive and negative symptom of participants with schizophrenia. For each symptom constructs, 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. The cumulative score ranges from 30 to 210.
13.	Change from Baseline in Clinical Global Impression - Severity Scale (CGI-S) [ Time Frame: Baseline to Day 225 ] The CGI-S is a 7-point scale used to measure the severity of illness for each participant. 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 participants.
14.	Change from Baseline in Clinical Global Impression - Improvement Scale (CGI-I) [ Time Frame: Day 57 to Day 225 ] The CGI-I scale measures the improvement of illness for each participant. Response choices include: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no changed, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
15.	Change from Baseline in Subjective Well-Being Under Neuroleptic Treatment-Short Form (SWN-S) [ Time Frame: Baseline to Day 225 ] The SWN-S is a participant self-rated scale developed to evaluate the participants perception of well-being while receiving antipsychotic medication. The questionnaire consists of 20 items and 5 subscales (mental functioning, social integration, emotional regulation, physical functioning, and self control). For items marked with a '+', items are rated 1 = not at all to 6 = very much. For items marked with a '-' items are rated 1 = very much to 6 = hardly at all. Total possible scores range from 20-120.
16.	Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline to Day 225 ] The MADRS measures symptoms of depression and is administered using a structured interview guide. The scale consists of 10 items, each with 7 defined grades of severity (0-6). Total scores ranges from 0-60 and a higher score indicates more depressive symptoms.
17.	Change from Baseline in Young Mania Rating Scale (YMRS) [ Time Frame: Baseline to Day 225 ] The YMRS is an 11-item, multiple-choice diagnostic questionnaire which psychiatrists use to assess the core symptoms of mania and is based on the participants subjective report of their condition. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Total score is summed of 11 items. Total score rage is from 0 to 60 and the higher score represent a worse outcome.
18.	Change from Baseline in Clinical Global Impression - Bipolar Version (CGI-BP) [ Time Frame: Baseline to Day 225 ] The CGI-BP scale refers to the global impression of the participants with respect to bipolar disorder. The scale rates the participant's severity of illness (CGI-BP-Severity: mania, depression, and overall bipolar illness) and change from preceding phase (CGI-BP change from preceding phase: mania, depression, and overall bipolar illness) based on a 7-point scale from 1 ('normal, not ill') to 7 ('very severely ill').

Eligibility


Minimum Age:	18 Years
Maximum Age:	64 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: A current diagnosis of schizophrenia or bipolar I disorder, as defined by DSM-5 criteria. Body mass index of 18 to 35 kg/m2. On a stable dose of an atypical oral antipsychotic medication for at least 2 months prior to screening. Exclusion Criteria: Participants who have: Met DSM-5 criteria for substance use disorder within the past 180 days. A positive drug screen for drugs of abuse 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. Females who are pregnant, breast-feeding, lactating, and/or have a positive pregnancy test result prior to receiving IMP. A negative serum pregnancy test must be confirmed prior to the first dose of IMP for all female participants. Any major surgery within 30 days prior to enrollment or scheduled/elective surgery during the trial. Evidence of organ dysfunction or any clinically significant deviation from normal in the physical, electrocardiographic, or clinical laboratory examinations. Participants currently in an acute relapse of schizophrenia. Participants with a current DSM-5 diagnosis other than schizophrenia or bipolar I disorder, including schizoaffective disorder, major depressive disorder, delirium, dementia, amnestic, or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, or antisocial personality disorder. Participants with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia. History of any significant drug allergy or known or suspected hypersensitivity, in particular to aripiprazole or other quinolinones. History of or current hepatitis or acquired immunodeficiency syndrome or carriers of HBsAg or anti-HCV, and/or HIV antibodies. Participants deemed intolerant of receiving injections. Participants who have had electroconvulsive therapy within 2 months of administration of IMP.

Contacts/Locations


Central Contact Person:	Wael Abdelrahman Telephone: 250 483 4512 Ext. 1 Email: AbdelrahmanWael@prahs.com
Locations:	United States, Arkansas
	Woodland International Research Group Little Rock, Arkansas, United States, 72211 Contact:Contact: Jim Aukstuolis
	Woodland International Research Group Rogers, Arkansas, United States, 72758 Contact:Contact: Robert Billingsley
	United States, California
	CITrials - Bellflower Bellflower, California, United States, 90706 Contact:Contact: Diane Highum
	Collaborative Neuroscience Network Garden Grove, California, United States, 92845 Contact:Contact: David Walling
	Synergy Research Centers Lemon Grove, California, United States, 91945 Contact:Contact: Mohammed Bari
	NRC Research Institute Orange, California, United States, 92868 Contact:Contact: Daniel Chueh
	California Neuropsychopharmacology Clinical Research Institute San Diego San Diego, California, United States, 92102
	Collaborative Neuroscience Network - South Bay Torrance, California, United States, 90502 Contact:Contact: Lara Shirikjian
	United States, Florida
	Research Centers of America Hollywood, Florida, United States, 33024 Contact:Contact: Peter Ventre
	Segal Institute For Clinical Research - West Broward Outpatient Clinic Miami Lakes, Florida, United States, 33016 Contact:Contact: Rishi Kakar
	United States, Georgia
	Atlanta Center for Medical Research - Atlanta Atlanta, Georgia, United States, 30331 Contact:Contact: Robert Riesenberg
	United States, Maryland
	CBH Health Gaithersburg, Maryland, United States, 20877 Contact:Contact: Robert Litman
	United States, Missouri
	St. Louis Clinical Trials Saint Louis, Missouri, United States, 63141 Contact:Contact: Daniel Gruener
	United States, Nevada
	Altea Research Institute - Las Vegas Las Vegas, Nevada, United States, 89102 Contact:Contact: Jelena Kunovac
	United States, New Jersey
	Hassman Research Institute Berlin, New Jersey, United States, 08009 Contact:Contact: Howard Hassman
	United States, Ohio
	Midwest Clinical Research Center Dayton, Ohio, United States, 45417 Contact:Contact: Otto Dueno
	United States, South Carolina
	Carolina Clinical Trials Charleston, South Carolina, United States, 29407 Contact:Contact: Eduardo Cifuentes
	United States, Texas
	Community Clinical Research Austin, Texas, United States, 78754 Contact:Contact: David Brown

IPDSharing


Plan to Share IPD:	Undecided

References


Citations:
Links:
Available IPD/Information: