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

Schizophrenia Clinical Trial

— ASPIRE  

Official title:

A 52-week, Multicenter, Open-label Study to Evaluate the Effectiveness of Aripiprazole Intramuscular Depot as Maintenance Treatment in Patients With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00731549
• Other study ID #: 31-08-248
• Status: Completed
• Phase: Phase 3
• First received: August 5, 2008
• Last updated: November 14, 2014
• Start date: December 2008
• Est. completion date: November 2013

Study information

• Verified date: November 2014
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: TGA - Therapeutic Goods AdministrationAustria: Federal Office for Safety in Health CareBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: CONEP and ANVISA; Bulgaria: Ministry of HealthChile: Instituto de Salud Pública de ChileChina: Food and Drug AdministrationCroatia: Ministry of Health and Social CareEstonia: The State Agency of MedicineFinland: FIMEA - Finnish Medicines AgencyFrance: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesGreece: EOF - The National Organisation for MedicinesHungary: National Institute of PharmacyIndia: Drugs Controller General of IndiaIsrael: Ministry of HealthMalaysia: Ministry of HealthMexico: Comiosion Federal Para la Proteccoin Contra Riesgos SanitariosNorway: NoMA - Norwegian Medicines AgencyPhilippines: Department of HealthPoland: Ministry of HealthPuerto Rico: FDA - Food and Drug AdministrationRomania: Ministry of Public HealthRussia: Pharmacological Committee, Ministry of HealthSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSlovakia: State Institute for Drug ControlSouth Africa: Medicines Control CouncilSouth Korea: Korea Food and Drug Administration (KFDA)Spain: Spanish Agency of MedicinesTaiwan: Department of HealthThailand: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1081
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Aripiprazole IM Depot
300mg or 400mg

Locations

Country	Name	City	State
United States	Study Site	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.	Covance

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Bulgaria,  Chile,  Croatia,  Estonia,  Finland,  France,  Hungary,  India,  Korea, Republic of,  Malaysia,  Mexico,  Norway,  Philippines,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit).	"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.	Baseline to Week 52/Last visit	No
Secondary	Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria.	"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.	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)	No
Secondary	Percentage of Participants Achieving Remission.	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.	Overall remission from Weeks 2,4,8,12,16,20,24,28,32,36,40,44,48 and 52	No
Secondary	Percentage of Participants Stable at Baseline and Remaining Stable at Week 28.	"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.	Baseline to Week 28	No
Secondary	Percentage of Participants With Time to First Exacerbation of Psychotic Symptoms/Impending Relapse.	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.	Baseline to Week 52	No
Secondary	Mean Change From Baseline to Endpoint (Last Visit) in Positive and Negative Syndrome Scale (PANSS) Total Score.	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.	Baseline, Weeks 12, 24, 52 and last visit	No
Secondary	Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score.	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.	Baseline, Weeks 12, 24, 52 and last visit	No
Secondary	Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales.	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.	Baseline, Weeks 12, 24, 52 and last visit	No
Secondary	Mean Clinical Global Impression of Improvement (CGI-I) Score.	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.	Weeks 2, 4, 12, 24, 52 and last visit	No
Secondary	Percentage of Participants Who Discontinued Due to All Causes.	Participants who discontinued due to any cause were noted. Limited concurrent treatment with oral aripiprazole was permitted as rescue therapy.	Baseline to Week 52	No