Clinical trial NCT03854409: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Bipolar I Disorder
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
name: H. Lundbeck A/S
First posted: 2019-02-26
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: Part A - Single Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 126
measure: Part B - Group 1: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 57
measure: Part B - Group 2: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 57
measure: Part A - Single Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 28
measure: Part B - Group 1: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 28
measure: Part B - Group 2: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 28
measure: Part A - Single Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 126
measure: Part B - Group 1: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 57
measure: Part B - Group 2: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 57
measure: 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
timeFrame: Day 1 to Day 126
measure: 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
timeFrame: Day 1 to Day 57
measure: 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
timeFrame: Day 1 to Day 57
measure: 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
timeFrame: Day 1 to Day 28
measure: Part B - Group 1: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 28
measure: Part B - Group 2: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 28
measure: 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
timeFrame: Day 1 to Day 126
measure: Part B - Group 1: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 57
measure: Part B - Group 2: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 57
measure: Part A - Single Dose Group: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 126
measure: Part B - Group 1: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 57
measure: Part B - Group 2: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 1 to Day 57
measure: Part A - Single Dose Group: Oral Clearance (CL/F) for Aripiprazole Only
timeFrame: Day 1 to Day 126
measure: Part B - Group 1: Oral Clearance (CL/F) for Aripiprazole Only
timeFrame: Day 1 to Day 57
measure: Part B - Group 2: Oral Clearance (CL/F) for Aripiprazole Only
timeFrame: Day 1 to Day 57
measure: Part A - Multiple Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole (Following the Fifth Dose Only)
timeFrame: Day 113 to Day 169
measure: Part A - Multiple Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 29, Day 57, Day 84, Day 113, Day 141 (All post-dose)
measure: Part A - Multiple Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 113 to Day 169
measure: 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
timeFrame: Day 113 to Day 169
measure: Part A - Multiple Dose Group: Terminal Phase Elimination Half-life (T1/2) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole
timeFrame: Day 113 to Day 169
measure: Part A - Multiple Dose Group: Oral Clearance (CL/F) (Following the Fifth Dose Only; for Aripiprazole Only)
timeFrame: Day 113 to Day 169
measure: Part A - Multiple Dose Group: Ratio of Dehydro-Aripiprazole to Aripiprazole C28 and AUC0-28 (Following the Fifth Dose Only)
timeFrame: Day 113 (following fifth dose) to Day 141
Secondary outcomes:
measure: Part A - Single Dose: Number of Participants with an Adverse Event (AE)
timeFrame: Day 1 to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Number of Participants with an Adverse Event (AE)
timeFrame: Day 1 to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Number of Participants with an Adverse Event (AE)
timeFrame: Day 1 to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Number of Participants with Markedly Abnormal Vital Sign Measurements
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Number of Participants with Markedly Abnormal Vital Sign Measurements
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Number of Participants with Markedly Abnormal Vital Sign Measurements
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Number of Participants with Markedly Abnormal Clinical Laboratory Results
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Number of Participants with Markedly Abnormal Clinical Laboratory Results
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Number of Participants with Markedly Abnormal Clinical Laboratory Results
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Change from Baseline in Serum Prolactin
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Change from Baseline in Serum Prolactin
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Change from Baseline in Serum Prolactin
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Number of Participants with Markedly Abnormal Physical Examination Results
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Number of Participants with Markedly Abnormal Physical Examination Results
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Number of Participants with Markedly Abnormal Physical Examination Results
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception
timeFrame: Day 1 immediately post-dose, 1 hour post-dose (+/- 15 minutes), Day 14 and Day 29
measure: Part A - Multiple Dose: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception
timeFrame: 1-hour post-dose Day 1, Day 29, Day 57, Day 85, Day 113
measure: Part B: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception
timeFrame: Day 1 immediately post-dose, 1 hour post-dose (+/- 15 minutes), Day 14 and Day 29
measure: Part A - Single Dose: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Number of Injection Site Related Adverse Events
timeFrame: End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Number of Injection Site Related Adverse Events
timeFrame: End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Number of Injection Site Related Adverse Events
timeFrame: End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)
timeFrame: Day 1 (predose) to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)
timeFrame: Day 1 (predose) to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)
timeFrame: Day 1 (predose) to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWN-S) Score
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWN-S) Score
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWNS) Score
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Change from Baseline in Young Mania Rating Scale (YMRS) Score
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Change from Baseline in Young Mania Rating Scale (YMRS) Score
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Change from Baseline in Young Mania Rating Scale (YMRS) Score
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
measure: Part A - Single Dose: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score
timeFrame: Baseline to End of Trial (Maximum 126 Days from First Dose)
measure: Part A - Multiple Dose: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score
timeFrame: Baseline to End of Trial (Maximum 169 Days from First Dose)
measure: Part B: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score
timeFrame: Baseline to End of Trial (Maximum 57 Days from First Dose)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Woodland International Research Group
state: Arkansas
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network
state: California
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Austin
country: United States
facility: Community Clinical Research
state: Texas
Study officials:
References: