Clinical trial NCT04030143: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Schizophrenia
Bipolar I Disorder
Keywords: Aripiprazole
Aripiprazole Intramuscular Depot
Gluteal Muscle
Long Acting Injection
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-23
Enrollment: 266
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to determine the safety and tolerability of multiple-dose administrations of aripiprazole, to establish the similarity of aripiprazole concentrations on the last day of the dosing interval following the final administration of aripiprazole into the gluteal muscle site, and to establish the similarity of aripiprazole exposure over the dosing interval following the administration of aripiprazole into the gluteal muscle site in adult participants with schizophrenia or bipolar I disorder.


Eligibility criteria: Inclusion Criteria:

* A current diagnosis of schizophrenia or bipolar I disorder, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
* Body mass index of 18 to 35 kilograms per meter square (kg/m\^2).
* 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 participants 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 investigational medicinal product (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, participants 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 Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies (anti-HCV), and/or Human immunodeficiency virus (HIV) antibodies.
* Participants deemed intolerant of receiving injections.
* Participants who have had electroconvulsive therapy within 2 months of administration of IMP.

Primary outcomes:
measure: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to 56 days (2M LAI 960 mg) or 28 days (IM depot 400 mg) post last dose of study drug (up to approximately 11 months)
measure: Number of Participants With Potentially Clinically Relevant Vital Signs Abnormalities
timeFrame: From first dose of study drug up to Day 225
measure: Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities
timeFrame: From first dose of study drug up to Day 225
measure: Number of Participants With Potentially Clinically Relevant Clinical Laboratory Abnormalities
timeFrame: From first dose of study drug up to Day 225
measure: Mean Change From Baseline in Simpson-Angus Neurologic Rating Scale (SAS) Total Score
timeFrame: Baseline, Week 32
measure: Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Score
timeFrame: Baseline, Week 32
measure: Mean Change From Baseline in Barnes Akathisia Rating Score (BARS) Global Score
timeFrame: Baseline, Week 32
measure: Visual Analog Scale (VAS) Scores for Pain Perception of Aripiprazole 2M LAI 960 mg
timeFrame: Day 1 (First injection) to Day 169 (Last injection)
measure: VAS Scores for Pain Perception of Aripiprazole IM Depot 400 mg
timeFrame: Day 1 (First injection) to Day 197 (Last injection)
measure: Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating After Aripiprazole 2M LAI 960 mg Injection
timeFrame: Day 1 (First injection) to Day 169 (Last injection)
measure: Number of Participants With Injection Site Evaluations (Pain, Redness, Swelling, Induration) Measured by Investigator Rating After Aripiprazole IM Depot 400 mg Injection
timeFrame: Day 1 (First injection) to Day 197 (Last injection)
measure: Number of Participants With Suicidality as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline to Day 225
measure: Plasma Concentration of Aripiprazole 56 Days Postdose (C56) of Aripiprazole 2M LAI 960 mg After the Fourth Dose
timeFrame: Day 225
measure: Plasma Concentration of Aripiprazole 28 Days Postdose (C28) of Aripiprazole IM Depot 400 mg After the Eighth Dose
timeFrame: Day 225
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to 28 Days (AUC0-28) of Aripiprazole After the Seventh and Eighth Doses of Aripiprazole IM Depot 400 mg
timeFrame: Days 169 (predose and 4, 8, 12 hours post dose), 170, 171, 173, 176, 178, 181, 183, 186, 190, 197 (predose and 4, 8, 12 hours post dose), 198, 199, 201, 204, 206, 209, 211, 214, 218, 225
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to 56 Days (AUC0-56) of Aripiprazole After the Fourth Dose of Aripiprazole 2M LAI 960 mg
timeFrame: Days 169 (predose and 4, 8, 12 hours post dose), 170, 171, 173, 176, 178, 181, 183, 186, 190, 197, 204, 211, 218, and 225
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Aripiprazole After First and Fourth Doses of Aripiprazole 2M LAI 960 mg
timeFrame: Days 1(predose [within 2 hours(h) prior to dosing]&4,8,12 h postdose),2,3,5,8,10,13,15,18,22,29,36,43,50,57(predose),85,113(predose),141,169(predose [within 2 h prior to dosing]& 4,8,12 h postdose),170,171,173,176,178,181,183,186,190,197,204,211,218 & 225
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of Aripiprazole After First and Fourth Doses of Aripiprazole 2M LAI 960 mg
timeFrame: Days 1(predose [within 2 hours(h) prior to dosing]&4,8,12 h postdose),2,3,5,8,10,13,15,18,22,29,36,43,50,57(predose),85,113(predose),141,169(predose [within 2 h prior to dosing]& 4,8,12 h postdose),170,171,173,176,178,181,183,186,190,197,204,211,218 & 225
measure: AUC0-56 After the First Dose of Aripiprazole 2M LAI 960 mg
timeFrame: Days 1 (predose and 4, 8, 12 hours post-dose), 2, 3, 5, 8, 10, 13, 15, 18, 22, 29, 36, 43, 50 and 57 (pre-dose)
measure: Plasma Concentration of Aripiprazole 56 Days (C56) After the First Dose of Aripiprazole 2M LAI 960 mg
timeFrame: Predose on Day 57
measure: AUC0-28 After the Fourth Dose of Aripiprazole 2M LAI 960 mg
timeFrame: Days 169 (predose and 4, 8, 12 hours postdose), 170, 171, 173, 176, 178, 181, 183, 186, 190, and 197
measure: Area Under the Plasma Concentration-Time Curve From Time 29 to 56 Days (AUC29-56) After the Fourth Dose of Aripiprazole 2M LAI 960 mg
timeFrame: Days 204, 211, 218, and 225
measure: Peak-to-Trough Percent Fluctuation (PTF%) After the Fourth Dose of Aripiprazole 2M LAI 960 mg
timeFrame: Days 169 (Predose [within 2 hours prior to dosing] and 4, 8, 12 hours post dose), 170, 171, 173, 176, 178, 181, 183, 186, 190, 197, 204, 211, 218, and 225
measure: Cmax of Aripiprazole After the First, Seventh, and Eighth Doses of Aripiprazole IM Depot 400 mg
timeFrame: Predose [within 2 hours prior to dosing; 4,8,12h postdose] on Days 1,169,197; Predose on Days 29,57,85,113,141; and on Days 2, 3, 5, 8, 10, 13, 15, 18, 22, 170, 171, 173, 176, 178, 181, 183, 186, 190,198, 199, 201, 204, 206, 209, 211, 214, 218, 225
measure: Tmax of Aripiprazole After the First, Seventh, and Eighth Doses of Aripiprazole IM Depot 400 mg
timeFrame: Predose [within 2 hours prior to dosing; 4,8,12h postdose] on Days 1,169,197; Predose on Days 29,57,85,113,141; and on Days 2, 3, 5, 8, 10, 13, 15, 18, 22, 170, 171, 173, 176, 178, 181, 183, 186, 190,198, 199, 201, 204, 206, 209, 211, 214, 218, 225
measure: AUC0-28 After the First Dose of Aripiprazole IM Depot 400 mg
timeFrame: Days 1 (predose and 4, 8, and 12 hours postdose), 2, 3, 5, 8, 10, 13, 15, 18, 22 and 29 (predose)
measure: Plasma Concentration of Aripiprazole 28 Days (C28) After the First Dose of Aripiprazole IM Depot 400 mg
timeFrame: Predose on Day 29
measure: PTF% After the Eighth Dose of Aripiprazole IM Depot 400 mg
timeFrame: Days 197 (Predose [within 2 hours prior to dosing] and 4, 8, 12 hours post dose),198, 199, 201, 204, 206, 209, 211, 214, 218, 225
measure: Plasma Concentration of Aripiprazole 7 Days Post First Dose (C7) of Aripiprazole 2M LAI 960 mg
timeFrame: Day 8
measure: Plasma Concentration of Aripiprazole Post First Dose (C14) of Aripiprazole IM Depot 400 mg
timeFrame: Day 15
measure: Mean Change From Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Total Score
timeFrame: Baseline, Week 32
measure: Mean Change From Baseline in Clinical Global Impression - Severity Scale (CGI-S) Score
timeFrame: Baseline, Week 32
measure: Mean Change From Baseline in Clinical Global Impression - Improvement Scale (CGI-I) Score
timeFrame: Baseline, Week 32
measure: Mean Change From Baseline in Subjective Well-Being Under Neuroleptic Treatment-Short Form (SWN-S) Total Score
timeFrame: Baseline, Week 32
measure: Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline, Week 32
measure: Mean Change From Baseline in Young Mania Rating Scale (YMRS) Total Score
timeFrame: Baseline, Week 32
measure: Mean Change From Baseline in Clinical Global Impression - Bipolar Version (CGI-BP) Severity of Illness Score
timeFrame: Baseline, Week 32
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Woodland International Research Group
state: Arkansas
city: Rogers
country: United States
facility: Woodland International Research Group
state: Arkansas
city: Bellflower
country: United States
facility: CITrials - Bellflower
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network
state: California
city: Glendale
country: United States
facility: California Clinical Trials Medical Group
state: California
city: Lemon Grove
country: United States
facility: Synergy Research Centers
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: San Diego
country: United States
facility: California Neuropsychopharmacology Clinical Research Institute San Diego
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network - South Bay
state: California
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Miami Lakes
country: United States
facility: Segal Institute For Clinical Research - West Broward Outpatient Clinic
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research - Atlanta
state: Georgia
city: Gaithersburg
country: United States
facility: CBH Health
state: Maryland
city: Saint Louis
country: United States
facility: St. Louis Clinical Trials
state: Missouri
city: Las Vegas
country: United States
facility: Altea Research Institute - Las Vegas
state: Nevada
city: Marlton
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Charleston
country: United States
facility: Carolina Clinical Trials
state: South Carolina
city: Austin
country: United States
facility: Community Clinical Research
state: Texas
Study officials:
References: