A Multiple Dose Safety, Tolerability and Pharmacokinetics Study in Adult Patients With Schizophrenia Following Administration of Aripiprazole IM Depot

NCT01870999 | Completed Phase 1 Results

• 1 other identifier: 31-05-244
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 7

Brief Summary

This study will evaluate the safety, tolerability, efficacy and pharmacokinetics of aripiprazole intramuscular (IM) depot multiple doses every 4 weeks in adult patients with schizophrenia.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Adverse Events as a Measure of Safety

  Safety and tolerability was assessed by the number of participants with adverse events (AE). An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a subject while enrolled in the study, whether or not it was considered drug-related by the investigator. Abnormal laboratory test findings were considered AEs if, in the opinion of the investigator, they represented an abnormal (ie, clinically significant) change from baseline for that individual participant.

  7 Months

• Aripiprazole Maximum Steady State Plasma Concentration (Css,Max)

  Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,max were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

  Pre-dose and 1 to 1344 hours post-dose at Month 5

• Aripiprazole Minimum Steady State Plasma Concentration (Css,Min)

  Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,min were determined directly from the observed data at 672 hours after the fifth monthly injection.

  672 hours post-dose at Month 5

• Aripiprazole Area Under the Concentration-time Curve at Steady-state (AUCτ)

  Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values of AUCτ were estimated using the linear trapezoidal rule during each dosing interval from 0 to 1344 hours post-dose.

  Pre-dose and 1 to 1344 hours post-dose at Month 5

Secondary Outcomes (13)

• Aripiprazole Maximum (Peak) Plasma Concentration (Tmax)

  Pre-dose and 1 to 1344 hours post-dose at Month 5

• Aripiprazole Steady-state Plasma Concentration (Css,Avg)

  Pre-dose and 1 to 1344 hours post-dose at Month 5

• Aripiprazole Terminal-phase Elimination Half-life (t1/2,z)

  Pre-dose and 1 to 1344 hours post-dose at Month 5

• Dehydro-aripiprazole Maximum Steady State Plasma Concentration (Css,Max)

  Pre-dose and 1 to 1344 hours post-dose at Month 5

• Dehydro-aripiprazole Minimum Steady State Plasma Concentration (Css,Min)

  Pre-dose and 1 to 1344 hours post-dose at Month 5

Study Arms (3)

400 mg Aripiprazole IM Depot

EXPERIMENTAL

400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Drug: aripiprazole IM depot; Drug: aripiprazole tablets

300 mg Aripiprazole IM Depot

EXPERIMENTAL

300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Drug: aripiprazole IM depot; Drug: aripiprazole tablets

200 mg Aripiprazole IM depot

EXPERIMENTAL

200 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Drug: aripiprazole IM depot; Drug: aripiprazole tablets

Interventions

aripiprazole IM depot DRUG

Aripiprazole IM depot supplied as 200 mg or 400 mg vials of lyophilized aripiprazole powder to prepare for IM injection.

200 mg Aripiprazole IM depot; 300 mg Aripiprazole IM Depot; 400 mg Aripiprazole IM Depot

aripiprazole tablets DRUG

Aripiprazole tablets 10 mg once daily in the morning for 14 days.

200 mg Aripiprazole IM depot; 300 mg Aripiprazole IM Depot; 400 mg Aripiprazole IM Depot

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria
• good physical health as determined by normal medical history, clinical laboratory results, electrocardiograms (ECGs) and physical examinations
• ability to provide informed consent and/or consent from a legally acceptable representation
• body mass index (BMI) of 18 to 35 kg/m\^2

You may not qualify if:

• sexually active males and females of child-bearing potential who are not practicing double barrier birth control or are not abstinent during the study plus 30 days for female or 90 days for males following the last dose of medication
• history of drug or alcohol abuse within 6 months and/or positive urine drug screen
• participants who consume alcohol beverages routinely
• participants who consume alcohol beverages during the screening period
• use of any antipsychotic medication, other prohibited psychotropic medication, and any cytochrome P450 2D6 (CYP2D6) and cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 inducers within 14 days
• use of any prescription medication unless approved by Medical Monitor or Study Director
• history of current hepatitis or carrier of HBsAg (Hepatitis B surface antigen) and/or Hepatitis C Virus antibodies (anti-HCV)
• females who are pregnant or lactating
• participants who have participated in any clinical trial involving a psychotropic medication within one month prior to enrollment; participants who have participated in a previous IM Depot study within the last 1 year; patients who have previously enrolled and received study medication in an aripiprazole IM Depot clinical trial
• donation of blood or plasma to a blood bank or in a clinical study (except a screening visit)within 30 days prior to enrollment
• any major surgery within 30 days prior to enrollment
• blood transfusion within 30 days prior to enrollment
• evidence of organ dysfunction or any clinically significant deviation from normal in the physical, electrocardiographic, or clinical laboratory examinations
• patient represents a significant risk of committing suicide based on history
• patients currently in an acute relapse

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (7)

Otsuka Investigative Site

Cerritos, California, 90703, United States

Location

Otsuka Investigative Site

Garden Grove, California, 92845, United States

Location

Otsuka Investigative Site

Glendale, California, 91206, United States

Location

Otsuka Investigative Site

Paramount, California, 90723, United States

Location

Otsuka Investigative Site

St Louis, Missouri, 63118, United States

Location

Otsuka Investigative Site

Willingboro, New Jersey, 08046, United States

Location

Otsuka Investigative Site

Austin, Texas, 78756, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Global Medical Affairs
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

800-562-3974

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2013
• First Posted: June 6, 2013
• Study Start: November 1, 2007
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: January 22, 2014
• Results First Posted: January 22, 2014

Record last verified: 2013-12

Locations

US (7)