Study to Determine the Pharmacokinetics, Safety & Tolerability of Aripiprazole in Adults With Schizophrenia

A Phase 1, Open-label, Single Ascending Dose, Parallel Arm Trial to Determine the Pharmacokinetics, Safety, and Tolerability of Aripiprazole 2 Month Intramuscular Depot Administered Gluteally in Adult Subjects With Schizophrenia

This trial will determine the Pharmacokinetics, safety and tolerability of single-dose Aripiprazole administered intramuscularly in adults with schizophrenia

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Aripiprazole

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
  • California
    • San Diego, California, United States, 92102
      • CNRI-San Diego
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male and female individuals between 18 and 64 years, inclusive, at screening with a current diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders: edition 5 (DSM-5)
• Body mass index (BMI) between 18 and 35 kg/m^2 at screening
• Male and female subjects who are surgically sterile, female subjects who have been postmenopausal for at least 12 consecutive months prior to screening or male/female subjects who agree to remain abstinent or practice 2 of the approved birth control methods from screening for at least 150 days after dose of Investigational Medical Product (IMP) for female subjects or 180 days after dose of IMP for male subjects.
• Documented history of previously tolerating Aripiprazole per investigator's judgment.

Exclusion Criteria:

• Met DSM-5 criteria for substance use disorder within past 180 days
• Positive drug screen for drugs of abuse
• Use of more than 1 antipsychotic medication at screening or baseline, except for oral Aripiprazole administered during tolerability testing and current antipsychotic medication
• Subjects may not receive varenicline beyond the screening visit.
• Subjects who had participated in any clinical trial involving a psychotropic medication within 1 month prior to administration of IMP
• Major surgery within 30 days prior to administration of IMP or surgery during the trial
• Subjects at significant risk of committing suicide based on history, psychiatric exams
• Subjects currently in an acute relapse of schizophrenia
• Subjects with a current DSM-5 diagnosis other than schizophrenia
• Subjects with a history of neuroleptic malignant syndrome, seizure disorder, or clinically significant tardive dyskinesia
• Subjects who have had electroconvulsive therapy within 2 months prior to administration of IMP
• Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP
• History of or current hepatitis or Acquired Immunodeficiency Syndrome or carriers of Hepatitis B surface antigen (HBsAG), Hepatitis C antigen (anti-HCV) and/or Human Immunodeficiency Virus (HIV) antibodies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Aripiprazole; single; gluteal	Drug: Aripiprazole; Injection; Other Names: Abilify Maintena
Experimental: Cohort 2; Aripiprazole; single; gluteal	Drug: Aripiprazole; Injection; Other Names: Abilify Maintena

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs) [safety and tolerability]	AEs will be monitored to assess safety and tolerability of drug	Screening Days -30 to Day 182 post dose/Early Termination
Clinical Laboratory Tests [safety and tolerability]	Hematology, clinical chemistry & urinalysis tests will be performed to assess the safety and tolerability of drug.	Screening Days -30 to Day 182 post dose/Early Termination
Electrocardiograms (ECGs) [Safety and tolerability]	Heart rate, RR, PR, WRS and WT intervals will be monitored to assess the safety and tolerability of the drug.	Screening Days -30 to Day 182 post dose/Early Termination
Vital Signs [safety and tolerability]	Systolic/diastolic blood pressure, heart rate and body temperature will be monitored to assess the safety and tolerability of the drug.	Screening Days -30 to Day 182 post dose/Early Termination
Suicidality via Columbia-Suicide Severity Rating Scale (C-SSRS) [safety and tolerability]	C-SSRS score will be monitored throughout the trial to assess the safety and tolerability of drug	Screening Days -30 to Day 182 post dose/Early Termination
Extrapyramidal Symptoms (EPS) Rating Scales	EPS score will be monitored to assess safety and tolerability of drug	Screening Days -30 to Day 182 post dose/Early Termination
Investigator's Assessment of Injection Site	The injection site will be monitored to assess the safety and tolerability of drug	Screening Days -30 to Day 182 post dose/Early Termination
Visual Analog Scale (VAS) Scores for Pain Perception	VAS score will be monitored to assess safety and tolerability of drug	Day 1 to Day 28 post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Maximum plasma concentration (Cmax)	The maximum plasma concentration of drug at injection site will be assessed for plasma Aripiprazole and its major metabolite dehydro-aripiprazole	Day 1 to Day 182/Early Termination
Pharmacokinetics - time of maximum plasma concentration (tmax)	The amount of time that the maximum plasma concentration of drug at injection site will be assessed for plasma Aripiprazole and its major metabolite dehydro-aripiprazole	Day 1 to Day 182/Early Termination
Pharmacokinetics - area under concentration-time curve (AUC) calculated from time zero to time t (AUCt)	AUCt will be assessed for plasma Aripiprazole and its major metabolite dehydro-aripiprazole to determine average concentration of drug over time	Day 1 to Day 182/Early Termination
Pharmacokinetics - AUC calculated from time to infinity	AUCinfinity will be assessed for plasma Aripiprazole and its major metabolite dehydro-aripiprazole to determine total drug exposure over time	Day 1 to Day 182/Early Termination
Pharmacokinetics - Terminal-phase elimination half-life (t1/2,z)	t1/2,z will be assessed for plasma Aripiprazole and its major metabolite dehydro-aripiprazole to determine drug persistence in the body	Day 1 to Day 182/Early Termination

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2017
• Primary Completion (Actual): April 18, 2018
• Study Completion (Actual): May 2, 2018

Study Registration Dates

• First Submitted: May 2, 2017
• First Submitted That Met QC Criteria: May 10, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): June 12, 2018
• Last Update Submitted That Met QC Criteria: June 11, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: 031-201-00104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No