Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia (ASPIRE)

This study has been completed.
Sponsor:
Collaborator:
Covance
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00731549
First received: August 5, 2008
Last updated: November 14, 2014
Last verified: November 2014
  Purpose

To evaluate the overall effectiveness of aripiprazole intramuscular (IM) depot as maintenance treatment in patients with schizophrenia.


Condition Intervention Phase
Schizophrenia
Drug: Aripiprazole IM Depot
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 52-week, Multicenter, Open-label Study to Evaluate the Effectiveness of Aripiprazole Intramuscular Depot as Maintenance Treatment in Patients With Schizophrenia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). [ Time Frame: Baseline to Week 52/Last visit ] [ Designated as safety issue: No ]
    "Stable" was defined as meeting all of the following criteria: Outpatient status; Positive and negative syndrome scale (PANSS) total score ≤ 80; Lack of specific psychotic symptoms on the PANSS as measured by a score of ≤ 4 on each of the following items (possible scores of 1 to 7 for each item): 1) conceptual disorganization 2) suspiciousness 3) hallucinatory behavior 4) unusual thought content; Clinical Global Impression of Severity (CGI-S) ≤ 4 (moderately ill); and Clinical Global Impression for Severity of Suicidality (CGI-SS) ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2. The percentage of stable participants at baseline who remain stable at endpoint (last visit) is described here.


Secondary Outcome Measures:
  • Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. [ Time Frame: Weeks 2,4,8,12,16,20,24,28,32,36,40,44,48,52, and Last visit (upto 4 weeks ± 3 days after completion or withdrawal) ] [ Designated as safety issue: No ]
    "Impending relapse criteria" was defined as meeting all the following criteria: 1) Clinical Global Impression of Improvement (CGI-I) ≥ 5 (minimally worse), AND an increase to score of >4 and absolute increase of ≥ 2 on the individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content); or an increase to score >4 and absolute increase of ≥ 4 on the combined 4 PANSS items on any of these PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) OR 2) Hospitalization due to worsening of psychotic symptoms, but excluding hospitalization for psychosocial reasons, OR 3) CGI-SS score of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2, OR 4) Violent behavior resulting in clinically relevant self-injury, injury to another person, or property damage.

  • Percentage of Participants Achieving Remission. [ Time Frame: Overall remission from Weeks 2,4,8,12,16,20,24,28,32,36,40,44,48 and 52 ] [ Designated as safety issue: No ]
    Remission is defined as a score of ≤ 3 on each of the following specific PANSS items, maintained for a period of six months: delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/posturing, blunted affect, social withdrawal, and lack of spontaneity.

  • Percentage of Participants Stable at Baseline and Remaining Stable at Week 28. [ Time Frame: Baseline to Week 28 ] [ Designated as safety issue: No ]
    "Stable" was defined as meeting all of the following criteria: Outpatient status; PANSS total score ≤ 80; Lack of specific psychotic symptoms on the PANSS as measured by a score of ≤ 4 on each of the following items (possible scores of 1 to 7 for each item): 1) conceptual disorganization 2) suspiciousness 3) hallucinatory behavior 4) unusual thought content; Clinical Global Impression of Severity (CGI-S) ≤ 4 (moderately ill); and Clinical Global Impression for Severity of Suicidality (CGI-SS) ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2. The percentage of stable participants at baseline who remain stable at Week 28 is described here.

  • Percentage of Participants With Time to First Exacerbation of Psychotic Symptoms/Impending Relapse. [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
    Participants who first time meet relapse criteria were considered as having an event at date of exacerbation of psychotic symptoms/impending relapse. Time to first event was calculated as the earliest date of meeting one of relapse criteria. Limited concurrent treatment with oral aripiprazole was permitted as rescue therapy.

  • Mean Change From Baseline to Endpoint (Last Visit) in Positive and Negative Syndrome Scale (PANSS) Total Score. [ Time Frame: Baseline, Weeks 12, 24, 52 and last visit ] [ Designated as safety issue: No ]
    PANSS total score (range 30-210) is the sum of the rating scores for 7 positive scale items, 7 negative scale items and 16 general psychopathology scale items from the PANSS scale. PANSS positive subscale score (range 7-49) is the sum of the rating scores for the 7 positive scale items from the PANSS scale. PANSS negative subscale score (range 7-49) is the sum of the rating scores for the 7 negative scale items from the PANSS scale. The severity of each scale is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms.

  • Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score. [ Time Frame: Baseline, Weeks 12, 24, 52 and last visit ] [ Designated as safety issue: No ]
    To assess CGI-S, the rater or physician will answer the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices include: 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.

  • Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales. [ Time Frame: Baseline, Weeks 12, 24, 52 and last visit ] [ Designated as safety issue: No ]
    PANSS positive subscale score (range 7-49) is the sum of the rating scores for the 7 positive scale items from the PANSS scale. Positive subscale consists of 7 positive symptom constructs: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). PANSS negative subscale score (range 7-49) is the sum of the rating scores for the 7 negative scale items from the PANSS scale. Negative subscale consists of 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive pathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking). The severity of each scale is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms.

  • Mean Clinical Global Impression of Improvement (CGI-I) Score. [ Time Frame: Weeks 2, 4, 12, 24, 52 and last visit ] [ Designated as safety issue: No ]
    To assess CGI-I the rater or physician will rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses will be compared to the participants condition at 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.

  • Percentage of Participants Who Discontinued Due to All Causes. [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
    Participants who discontinued due to any cause were noted. Limited concurrent treatment with oral aripiprazole was permitted as rescue therapy.


Enrollment: 1081
Study Start Date: December 2008
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Active Treatment of aripiprazole IM depot (300mg or 400mg)
Drug: Aripiprazole IM Depot
300mg or 400mg
Other Name: Oral Aripiprazole

Detailed Description:

This will be an open-label, uncontrolled study which will enroll subjects from Phase 4 of Study 31-07-246 and Phase 3 of Study 31- 07-247 and new subjects not participating in Studies 246/247. The treatment history of subjects prior to enrollment in the open-label study will vary according to the design of the pivotal double-blind study (i.e., 31-07-246 or 31-07-247).

This open-label study will be comprised of phases similar to the pivotal double-blind studies (i.e., Studies 246/247): a screening phase (if applicable), a conversion phase (Phase 1, if applicable), an oral stabilization phase (Phase 2), and an IM depot open-label maintenance phase (Phase 3). Phase 3 will be a 52-week treatment period with a 26-week follow-up period.

During Phase 3 (the open-label maintenance phase) oral aripiprazole rescue medication will be allowed for subjects who do not meet stability criteria or meet the criteria for impending relapse/exacerbation of psychotic symptoms.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as require by IRB/IEC), prior to the initiation of any protocol-required procedures.
  • Male and female subjects 18 to 65 years of age, inclusive, at time of informed consent.
  • Subjects who complete Studies 246/247 or who withdrew from the double-blind maintenance phase of either study (Phase 4 of Study 246 or Phase 3 of Study 247), or new subjects not participating in Studies 246/247.
  • # Subjects who, in the investigator's judgment, require chronic treatment with an antipsychotic medication.
  • Subjects able to understand the nature of the study and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, IM depot injection, discontinuation of prohibited concomitant medications, who can read and understand the written word in order to complete patient-reported outcomes measures, and who can be reliably rated on assessment scales.

Exclusion Criteria:

  • 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.
  • Subjects with schizophrenia that are considered resistant/refractory to antipsychotic treatment by history or response only to clozapine.
  • Subjects with a significant risk of violent behavior or a significant risk of committing suicide based on history or investigator's judgment.
  • Subjects who currently meet DSM-IV-TR criteria for substance dependence; including alcohol and benzodiazepines, but excluding caffeine and nicotine, or two positive drug screens for cocaine.
  • Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones.
  • Subjects with a history of hypersensitivity to antipsychotic agents.
  • Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia at screening.
  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: NCT00731549

  Show 214 Study Locations
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Covance
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT00731549     History of Changes
Other Study ID Numbers: 31-08-248
Study First Received: August 5, 2008
Results First Received: November 4, 2014
Last Updated: November 14, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: TGA - Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: CONEP and ANVISA; Bulgaria: Ministry of Health
Chile: Instituto de Salud Pública de Chile
China: Food and Drug Administration
Croatia: Ministry of Health and Social Care
Estonia: The State Agency of Medicine
Finland: FIMEA - Finnish Medicines Agency
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Greece: EOF - The National Organisation for Medicines
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Israel: Ministry of Health
Malaysia: Ministry of Health
Mexico: Comiosion Federal Para la Proteccoin Contra Riesgos Sanitarios
Norway: NoMA - Norwegian Medicines Agency
Philippines: Department of Health
Poland: Ministry of Health
Puerto Rico: FDA - Food and Drug Administration
Romania: Ministry of Public Health
Russia: Pharmacological Committee, Ministry of Health
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Thailand: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Aripiprazole
IM Depot
Schizophrenia
Intramuscular

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Aripiprazole
Antipsychotic Agents
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 March 01, 2015