Safety and Tolerability Trial of Aripiprazole IM Depot Treatment in Adult Subjects With Schizophrenia Stabilized on Oral Antipsychotics Other Than Aripiprazole

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01552772
First received: February 13, 2012
Last updated: October 8, 2014
Last verified: October 2014
  Purpose

This study will test the safety of an aripiprazole injection in subjects with schizophrenia that are currently taking oral antipsychotic medication other than aripiprazole. Subjects in this study will receive one injection of aripiprazole and will need to stop taking their other antipsychotic medication two weeks after the injection. The study will last one month. Subjects will be required to come to a clinic for evaluations and drug and urine collection five times during the course of the study.


Condition Intervention Phase
Schizophrenia
Drug: Aripiprazole IM Depot
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Safety and Tolerability Trial of Aripiprazole IM Depot Treatment Initiation in Adult Subjects With Schizophrenia Stabilized on Atypical Oral Antipsychotics Other Than Aripiprazole

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AE). [ Time Frame: From the time the informed consent (ICF) was signed until follow-up at 30 days after the last trial visit (Day 28). ] [ Designated as safety issue: Yes ]
    An 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 study physician. 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. TEAE stands for treatment emergent adverse events.


Secondary Outcome Measures:
  • Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Observed Cases (OC) Data. [ Time Frame: Baseline, Week 1, 2, 4 and Last visit (Day 28). ] [ Designated as safety issue: No ]
    The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

  • Change From Baseline in Total Score of PANSS for Last Observation Carried Forward (LOCF) Data. [ Time Frame: Baseline, Week 1, 2 and 4 ] [ Designated as safety issue: No ]
    The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

  • Change From Baseline in PANSS Positive Sub-scale Score for OC Data. [ Time Frame: Baseline, Week 1, 2, 4 and Last visit (Day 28). ] [ Designated as safety issue: No ]
    The Positive and Negative Syndrome Scale (PANSS) consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

  • Change From Baseline in PANSS Positive Sub-scale Score for LOCF Data. [ Time Frame: Baseline, Week 1, 2 and 4 ] [ Designated as safety issue: No ]
    The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

  • Change From Baseline in PANSS Negative Sub-scale Score for OC Data. [ Time Frame: Baseline, Week 1, 2, 4 and Last visit (Day 28). ] [ Designated as safety issue: No ]
    The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

  • Change From Baseline in PANSS Negative Sub-scale Score for LOCF Data. [ Time Frame: Baseline, Week 1, 2 and 4 ] [ Designated as safety issue: No ]
    The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

  • Change From Baseline in Clinical Global Impression Severity (CGI-S) Score in OC Data. [ Time Frame: Baseline, Week 1, 2, 4 and Last visit (Day 28). ] [ Designated as safety issue: No ]
    The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.

  • Change From Baseline in CGI-S Score in LOCF Data. [ Time Frame: Baseline, Week 1, 2 and 4. ] [ Designated as safety issue: No ]
    The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.

  • Clinical Global Impression Improvement (CGI-I) Scale Score in OC Data. [ Time Frame: Week 1, 2, 4 and Last visit (Day 28). ] [ Designated as safety issue: No ]
    The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition a baseline. Response choices include: 0 = not assessed; 1 =very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 =minimally worse; 6 = much worse; and 7 = very much worse.

  • CGI-I Scale Score in LOCF Data. [ Time Frame: Week 1, 2 and 4 ] [ Designated as safety issue: No ]
    The efficacy of trial medication were rated for each participant using the Clinical Global Impression Improvement (CGI-I) scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition a baseline. Response choices include: 0 = not assessed; 1 =very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 =minimally worse; 6 = much worse; and 7 = very much worse.


Enrollment: 60
Study Start Date: January 2012
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aripiprazole IM Depot Drug: Aripiprazole IM Depot
400 mg intramuscular injection of aripiprazole
Other Name: Abilify

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female individuals between 18 and 64 years of age, inclusive, with a diagnosis of schizophrenia as defined by DSM-IV-TR criteria.
  2. Good physical health as determined by no clinically significant deviation from normal in medical history, clinical laboratory determination, ECGs, or physical examinations.
  3. Ability to provide written informed consent or consent obtained from a legally acceptable representative (as required by IRB) prior to the initiation of any protocol-required procedures.
  4. Body mass index of 18 to 35 kg/m2, inclusive.
  5. Prior history of tolerating aripiprazole.
  6. Subjects must be treated with one of the following atypical oral antipsychotic medications: risperidone, olanzapine, quetiapine, ziprasidone, or paliperidone and be clinically stable, per the investigator's judgment, for 14 days prior to the administration of aripiprazole IM depot

Exclusion Criteria:

  1. Sexually active males who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during the trial and for 180 days following the last dose of trial medication, or have not had an orchidectomy or sexually active females of childbearing potential who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during the trial and for 150 days following the last dose of trial medication. Abstinence will be permitted if it is confirmed and documented at every trial visit. If employing birth control, 2 of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control depot injections, implant, condom or sponge with spermicide. Note: Women of childbearing potential (WOCBP) are defined as all women unless they have had an oophorectomy or hysterectomy or have been postmenopausal for 12 consecutive months.
  2. Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days; including alcohol and benzodiazepines, but excluding caffeine and nicotine. Subjects with a positive drug screen for cocaine or other drugs of abuse (excluding stimulants and other prescribed medications and marijuana).a
  3. Subjects likely to require prohibited concomitant therapy during the trial, and use of any CYP2D6 and CYP3A4 inhibitors, or CYP3A4 inducers within 14 days prior to dosing and for the duration of the trial.
  4. Females who are pregnant or lactating.
  5. 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 IM depot trial within the last 6 months; or who had previously enrolled and received trial medication in an aripiprazole IM depot clinical trial.
  6. Any major surgery within 30 days prior to enrollment.
  7. Evidence of organ dysfunction or any clinically significant deviation from normal in physical, electrocardiographic, or clinical laboratory examinations.
  8. Subjects who have a significant risk of committing suicide based on history or routine psychiatric status examination
  9. Subjects currently in an acute relapse of schizophrenia.
  10. Subjects with a current DSM-IV-TR diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, amnestic or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
  11. Subjects who were considered treatment-resistant to antipsychotic medication. (Subjects needed to have shown a previous response to an antipsychotic medication other than clozapine.)
  12. Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia.
  13. Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01552772

Locations
United States, California
South Coast Clinical Trials
Anaheim, California, United States, 92804
Comprehensive Clinical Development
Cerritos, California, United States, 90703
Collaborative Neuroscience Network
Garden Grove, California, United States, 92845
South Coast Clinical Trials
Norwalk, California, United States, 90650
CNRI-San Diego
San Diego, California, United States, 92102
Neuropsychiatric Research Center of Orange County
Santa Ana, California, United States, 92701
United States, District of Columbia
Comprehensive Clinical Development
Washington, District of Columbia, United States, 20016
United States, Florida
Accurate Clinical Trials
Kissimmee, Florida, United States, 34741
Compass Research, LLC
Orlando, Florida, United States, 32806
United States, Missouri
St. Louis Clinical Trials
St. Louis, Missouri, United States, 63118
United States, Texas
Community Clinical Research
Austin, Texas, United States, 78754
Pillar Clinical Research
Dallas, Texas, United States, 75243
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Stacy Wu, MD Otsuka Pharmaceutical Development and Commercialization
  More Information

No publications provided by Otsuka Pharmaceutical Development & Commercialization, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01552772     History of Changes
Other Study ID Numbers: 31-11-289
Study First Received: February 13, 2012
Results First Received: September 2, 2014
Last Updated: October 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Safety
Tolerability
Schizophrenia
Aripiprazole

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Antipsychotic Agents
Aripiprazole
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 20, 2014