Safety and Tolerability Study of Aripiprazole IM Depot in Adult Subjects With Schizophrenia

NCT01909466 | Completed Phase 1 Results

• 1 other identifier: 31-12-298
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 11

Brief Summary

To determine the safety and tolerability of multiple-dose administrations of aripiprazole intramuscular (IM) depot in the deltoid muscle in adult subjects with schizophrenia

Conditions

Schizophrenia; Mental Disorder; Nervous System Diseases

Keywords

OPC-14597; Aripiprazole; Schizophrenia

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Adverse Events (AEs).

  AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the investigator. A serious adverse event (SAE) was any untoward medical occurrence that resulted in death or was life threatening or required inpatient hospitalization or prolonged hospitalization. A treatment-emergent AE (TEAE) was defined as an AE that started after start of study medication or an AE that continued from baseline and that worsened, was serious, was study medication related, or resulted in death, discontinuation, interruption, or reduction of study medication.

  AEs were recorded from the time the informed consent was signed until follow-up for 28 days after last

• Mean Visual Analog Scale (VAS) Score for Rating of Pain at the Injection Site.

  Participants assessed the pain associated with injection of aripiprazole IM using the VAS instrument. This was done approximately 30 minutes pre-dose and 1 hour (±15 min) Post-dose on Days 1, 29, 57, 85 and 113. For the first injection, the pre-dose assessment was of the current injection site. For the injections 2 through 5, the pre-dose assessment was of the prior injection site. Investigator's Assessment of Most Recent Injection Site including pain, swelling, redness, and induration were reported in 4-point categorical scale (1 = absent, 2 = mild, 3 = moderate and 4 = severe) by first injection site at each injection.

  Days 1 and 113

• Mean Change From Baseline in Suicidal Ideation Intensity Total Score Via Columbia-suicide Severity Rating Scale (C-SSRS).

  Suicidality was monitored throughout the trial using C-SSRS. The C-SSRS addresses the need for standardized classification of suicide reports to assess suicide risk. This scale consisted of Baseline evaluation that assessed the lifetime experience of the participant with suicidal events and suicidal ideation and a post baseline evaluation that focuses on suicidality since the last trial visit. The C-SSRS since last visit form were completed on Day 1 pre-dose and prior to dosing on Days 29, 57, 85, 113, 141/ Early Termination(ET) and prior to pharmacokinetics(PK) sampling on Days 8, 15, 22, 120, 127 and 134. The suicidal ideation intensity total score was the sum of suicidal ideation severity rating scores for frequency, duration, controllability, deterrents, and reasons for ideation. For each item, each participant got an intensity score from 0(none) to 5(worst). Therefore,the suicidal ideation intensity total score range from 0 to 25, with a score of 0 given for no suicidal ideation.

  Baseline to Last Visit (Day 141)

• Mean Change From Baseline Measured by Extrapyramidal Symptoms (EPS) by Simpson-Angus Scale (SAS).

  The SAS consisted 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). The SAS Total Score was the sum of the scores for all 10 items. SAS total score can range from 10 to 50. Each item was rated on a 5-point scale, with a score of 1 =absence of symptoms and a score of 5 =severe condition.

  Baseline to Week 20

• Mean Change From Baseline Measured by EPS by Abnormal Involuntary Movement Scale (AIMS).

  The AIMS assessment consisted 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) were observed unobtrusively while the participant was at rest (e.g., in the waiting room), and the study physician would make global judgments on the participant's dyskinesia's (items 8 through 10). These items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Overall AIMS scores range from 0 to 42.

  Baseline to Week 20

• Mean Change From Baseline Measured by EPS by Barnes Akathisia Rating Scale (BARS).

  The BARS consisted of 4 items related to akathisia: objective observation of akathisia by the study physician, subjective feelings of restlessness by the participant, participant distress due to akathisia, and global evaluation of akathisia. To complete this scale, participants were observed while they were seated and then stood for a minimum of 2 minutes in each position. Symptoms observed in other situations (e.g., while engaged in neutral conversation or engaged in activity on the ward) may also be rated. Subjective phenomena were to be elicited by direct questioning. The first 3 items were rated on a 4-point scale, with a score of 0 = absence of symptoms and a score of 3 = severe condition. The global clinical evaluation were made on a 6-point scale, (0=absent, 1=questionable, 2=mild, 3=moderate, 4=marked, 5=severe).

  Baseline to Week 20

Secondary Outcomes (11)

• Mean Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS).

  Baseline to Week 20

• Mean Change From Baseline in PANSS Positive Sub-scale Score.

  Baseline to Week 20

• Mean Change From Baseline in PANSS Negative Sub-scale Score.

  Baseline to Week 20

• Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score.

  Baseline to Week 20

• Clinical Global Impression-Improvement (CGI-I) Score.

  Baseline to Week 20

Study Arms (2)

Gluteal Injection

OTHER

Drug: Aripiprazole, OPC-14597

Deltoid Injection

OTHER

Drug: Aripiprazole, OPC-14597

Interventions

Aripiprazole, OPC-14597 DRUG

5 monthly applications of 400 mg of aripiprazole IM depot, where the first application is in the gluteal or deltoid muscle followed by 4 monthly administrations to the deltoid muscle

Deltoid Injection; Gluteal Injection

Eligibility Criteria

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

You may qualify if:

• Male and female individuals between 18 and 64 years, inclusive, at the time of informed consent.
• Prior history of tolerating aripiprazole per investigator's judgement.

You may not qualify if:

• Subjects who have met DSMV-IV-TR criteria for substance dependence within the past 180 days.
• Subjects who use more than one antipsychotic medication at screening.
• Use of any CYP2D6 and CYP3A4 inhibitors, or CYP3A4 inducers within 14 days prior to dosing and for the duration of the trial.
• Subjects who participated in any clinical trial involving a psychotropic medication within 1 month prior to enrollment.
• Subjects currently in an acute relapse of schizophrenia.
• Subjects with a current DSMV-IV-TR diagnosis other than schizophrenia.
• Subjects who are considered treatment-resistant to antipsychotic medications.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• H. Lundbeck A/S: collaborator

Study Sites (11)

Comprehensive Clinical Development

Cerritos, California, 90703, United States

Location

Collaborative Neuroscience Network, Inc.

Garden Grove, California, 92845, United States

Location

CNRI-San Diego

San Diego, California, 92101, United States

Location

Comprehensive Clinical Development

Washington D.C., District of Columbia, 20016, United States

Location

Scientific Clinical Research, Inc.

Fort Lauderdale, Florida, 33308, United States

Location

Compass Research North, LLC

Leesburg, Florida, 34748, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30308, United States

Location

St. Louis Clinical Trials

St Louis, Missouri, 63118, United States

Location

CRI Lifetree

Marlton, New Jersey, 08053, United States

Location

CRI Lifetree

Philadelphia, Pennsylvania, 19139, United States

Location

Community Clinical Research, Inc.

Austin, Texas, 78754, United States

Location

Related Publications (1)

• Raoufinia A, Peters-Strickland T, Nylander AG, Baker RA, Eramo A, Jin N, Bricmont P, Repella J, McQuade RD, Hertel P, Larsen F. Aripiprazole Once-Monthly 400 mg: Comparison of Pharmacokinetics, Tolerability, and Safety of Deltoid Versus Gluteal Administration. Int J Neuropsychopharmacol. 2017 Apr 1;20(4):295-304. doi: 10.1093/ijnp/pyw116.

  PMID: 28204607 DERIVED

MeSH Terms

Conditions

Schizophrenia; Mental Disorders; Nervous System Diseases

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic 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 and Commercialization, Inc.

800 562-3974

Study Officials

• Kimberly Largay, MD

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

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: July 24, 2013
• First Posted: July 26, 2013
• Study Start: July 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: April 1, 2014
• Last Updated: July 1, 2015
• Results First Posted: June 2, 2015

Record last verified: 2015-06

Locations

US (11)