Open-label Study to Compare Hospitalization Rates of Schizophrenic Patients Treated With Oral Antipsychotics Versus IM Depot Aripiprazole (ARRIVE- EU)

• ClinicalTrials.gov Identifier: NCT01509053
• Recruitment Status: Terminated
• First Posted: January 12, 2012
• Results First Posted: January 16, 2014
• Last Update Posted: March 4, 2015
• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Information provided by (Responsible Party): Otsuka Pharmaceutical Development & Commercialization, Inc.

• Study Type: Interventional
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Schizophrenia
• Interventions: Drug: Aripiprazole (Abilify®) IM Depot Injection; Drug: Oral aripiprazole
• Enrollment: 30

Participant Flow

Recruitment Details
Pre-assignment Details	This study included a Tolerability Assessment Phase A (if applicable), an Open-Label Aripiprazole IM Depot Phase B and an Open-Label Aripiprazole IM Depot Extension Phase C.

Arm/Group Title	Oral Aripiprazole Tablets and Aripiprazole IM Depot Injection
Arm/Group Description	Patients who had no history of tolerability to oral aripiprazole received 10-15 mg/day (up to 30 mg/day) oral aripiprazole for 1 to 4 weeks to determine tolerability in the Tolerability Assessment Phase (A) prior to receiving treatment with aripiprazole IM Depot. In the Open-label Aripiprazole IM Depot Phase (B), participants received aripiprazole intramuscular (IM) Depot 400 mg injection (dosage could be adjusted to 300 mg at the investigator's discretion) monthly in the clinic for a total of 6 injections + concomitant oral aripiprazole 10-15 mg/day for the first 14 days. Participants at the investigator's discretion were eligible to continue to receive aripiprazole IM depot (400 or 300 mg) injection monthly in the Open-label Aripiprazole IM Depot Extension phase (C). Oral aripiprazole was available as rescue medication if necessary.
Period Title: Oral Aripirazole (Phase A)
Started	19
Completed	8
Not Completed	11
Reason Not Completed
Sponsor discontinued study	11
Period Title: Aripiprazole IM Depot Treatment Phase(B)
Started	19 [1]
Completed	3
Not Completed	16
Reason Not Completed
Adverse Event	1
Sponsor discontinued study	13
Subject was withdrawn by investigator	1
Subject withdrew consent	1
[1] Includes 8 patients from Phase A + 11 patients who entered directly into Phase B.
Period Title: Aripiprazole IM Depot Extension Phase(C)
Started	3
Completed	0
Not Completed	3
Reason Not Completed
Sponsor discontinued study	3

Baseline Characteristics

Arm/Group Title		All Participants
Arm/Group Description		Patients who had no history of tolerability to oral aripiprazole received 10-15 mg/day (up to 30 mg/day) oral aripiprazole for 1 to 4 weeks to determine tolerability in the Tolerability Assessment Phase (A) prior to receiving treatment with aripiprazole IM Depot. In the Open-label Aripiprazole IM Depot Phase (B), participants received aripiprazole intramuscular (IM) Depot 400 mg injection (dosage could be adjusted to 300 mg at the investigator's discretion) monthly in the clinic for a total of 6 injections + concomitant oral aripiprazole 10-15 mg/day for the first 14 days. Participants at the investigator's discretion were eligible to continue to receive aripiprazole IM depot (400 or 300 mg) injection monthly in the Open-label Aripiprazole IM Depot Extension phase (C). Oral aripiprazole was available as rescue medication if necessary.
Overall Number of Baseline Participants		30
Baseline Analysis Population Description		Baseline measures are based on all enrolled participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	30 participants
		43.9 (12.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants
	Female	10 33.3%
	Male	20 66.7%

Outcome Measures

1. Primary Outcome

Title	Comparison of Inpatient Psychiatric Hospitalization Rates
Description	The comparison of inpatient psychiatric hospitalization rates (proportion of patients with ≥1 inpatient psychiatric hospitalizations) between the retrospective period Months 4-6 (Weeks-12 to -24) while on oral standard of care antipsychotic treatment and the prospective period Phase B Months 4-6 (Weeks 12 to 24) after the switch to aripiprazole IM depot.
Time Frame	Retrospective period Months 4-6; Prospective period Months 4-6

Outcome Measure Data

Analysis Population Description

Due to the low number of enrolled patient and the sponsor's early termination of the study, the primary efficacy endpoint was not evaluated.

Arm/Group Title	Aripiprazole IM Depot Injection	Standard of Care
Arm/Group Description:	Patients who had no history of tolerability to oral aripiprazole received 10-15 mg/day (up to 30 mg/day) oral aripiprazole for 1 to 4 weeks to determine tolerability in the Tolerability Assessment Phase (A) prior to receiving treatment with aripiprazole IM Depot. In the Open-label Aripiprazole IM Depot Phase (B), participants received aripiprazole intramuscular (IM) Depot 400 mg injection (dosage could be adjusted to 300 mg at the investigator's discretion) monthly in the clinic for a total of 6 injections + concomitant oral aripiprazole 10-15 mg/day for the first 14 days. Oral aripiprazole was available as rescue medication if necessary.	Patients who received oral antipsychotic treatment as standard of care in clinical practice.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

2. Secondary Outcome

Title	Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score
Description	The PANSS consisted of 3 subscales with a total of 30 symptom constructs each rated on a 7-point scale where 1=absence of symptoms to 7=extremely severe symptoms. The Positive Subscale consisted of 7 positive symptom constructs with a possible subscale score of 7 to 49, the Negative Subscale consisted of 7 negative symptom constructs with a possible subscale score of 7 to 49 and the General Psychopathology Subscale consisted of 16 symptom constructs for a possible subscale score of 16 to 112. The PANSS Total Score ranged from 30 (best) to 210 (worst; indicating more severe symptoms). A Negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Due to the low number of enrolled patients and the sponsor's early termination of the study, this endpoint was not evaluated.

Arm/Group Title	Aripiprazole IM Depot Injection
Arm/Group Description:	Patients who had no history of tolerability to oral aripiprazole received 10-15 mg/day (up to 30 mg/day) oral aripiprazole for 1 to 4 weeks to determine tolerability in the Tolerability Assessment Phase (A prior to receiving treatment with aripiprazole IM Depot. In the Open-label Aripiprazole IM Depot Phase (B), participants received aripiprazole intramuscular (IM) Depot 400 mg injection (dosage could be adjusted to 300 mg at the investigator's discretion) monthly in the clinic for a total of 6 injections + concomitant oral aripiprazole 10-15 mg/day for the first 14 days. Oral aripiprazole was available as rescue medication if necessary.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

3. Secondary Outcome

Title	Change From Baseline in PANSS Positive and Negative Subscale Scores
Description	The PANSS Positive Subscale consisted of 7 symptom constructs rated on a 7-point scale where 1=absence of symptoms to 7=extremely severe symptoms. The total score on the Positive Subscale ranged from 7 to 49 with a higher score indicating more severe symptoms. The PANSS Negative Subscale consisted of 7 symptom constructs rated on a 7-point scale where 1=absence of symptoms to 7=extremely severe symptoms. The total score on the Negative Subscale ranged from 7 to 49 with a higher score indicating more severe symptoms. A Negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Due to the low number of enrolled patients and the sponsor's early termination of the study, this endpoint was not evaluated.

Arm/Group Title	Aripiprazole IM Depot Injection
Arm/Group Description:	Patients who had no history of tolerability to oral aripiprazole received 10-15 mg/day (up to 30 mg/day) oral aripiprazole for 1 to 4 weeks to determine tolerability in the Tolerability Assessment Phase (A) prior to receiving treatment with aripiprazole IM Depot. In the Open-label Aripiprazole IM Depot Phase (B), participants received aripiprazole intramuscular (IM) Depot 400 mg injection (dosage could be adjusted to 300 mg at the investigator's discretion) monthly in the clinic for a total of 6 injections + concomitant oral aripiprazole 10-15 mg/day for the first 14 days. Oral aripiprazole was available as rescue medication if necessary.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

4. Secondary Outcome

Title	Clinical Global Impression of Severity (CGI-S) Score
Description	The severity of illness for each participant was rated using the CGI-S scale. The investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" using an 8-point scale where 0=not assessed to 7=among the most extremely ill patients.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Due to the low number of enrolled patients and the sponsor's early termination of the study, this endpoint was not evaluated.

Arm/Group Title	Aripiprazole IM Depot Injection
Arm/Group Description:	Patients who had no history of tolerability to oral aripiprazole received 10-15 mg/day (up to 30 mg/day) oral aripiprazole for 1 to 4 weeks to determine tolerability in the Tolerability Assessment Phase (A) prior to receiving treatment with aripiprazole IM Depot. In the Open-label Aripiprazole IM Depot Phase (B), participants received aripiprazole intramuscular (IM) Depot 400 mg injection (dosage could be adjusted to 300 mg at the investigator's discretion) monthly in the clinic for a total of 6 injections + concomitant oral aripiprazole 10-15 mg/day for the first 14 days. Oral aripiprazole was available as rescue medication if necessary.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

5. Secondary Outcome

Title	Clinical Global Impression of Improvement (CGI-I) Score
Description	The participant's overall improvement was rated for each participant using the CGI-I scale. The investigator rated the participant's total improvement by answering the following question: "Compared to his/her condition at baseline (prior to randomization), how much has the patient changed?" using an 8-point scale where 0=not assessed, 1=very much improved to 7=very much worse. Lower scores indicated improvement.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Due to the low number of enrolled patients and the sponsor's early termination of the study, this endpoint was not evaluated.

Arm/Group Title	Aripiprazole IM Depot Injection
Arm/Group Description:	Patients who had no history of tolerability to oral aripiprazole received 10-15 mg/day (up to 30 mg/day) oral aripiprazole for 1 to 4 weeks to determine tolerability in the Tolerability Assessment Phase (A) prior to receiving treatment with aripiprazole IM Depot. In the Open-label Aripiprazole IM Depot Phase (B), participants received aripiprazole intramuscular (IM) Depot 400 mg injection (dosage could be adjusted to 300 mg at the investigator's discretion) monthly in the clinic for a total of 6 injections + concomitant oral aripiprazole 10-15 mg/day for the first 14 days. Oral aripiprazole was available as rescue medication if necessary.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Oral Aripiprazole (Phase A)	Aripiprazole IM Depot (Phase B)	Aripiprazole IM Depot (Phase C)
Arm/Group Description	Patients who had no history of tolerability to oral aripiprazole received 10-15 mg/day (up to 30 mg/day) oral aripiprazole for 1 to 4 weeks to determine tolerability in the Tolerability Assessment Phase (A) prior to receiving treatment with aripiprazole IM Depot.	In the Open-label Aripiprazole IM Depot Phase (B), participants received aripiprazole intramuscular (IM) Depot 400 mg injection (dosage could be adjusted to 300 mg at the investigator's discretion) monthly in the clinic for a total of 6 injections + concomitant oral aripiprazole 10-15 mg/day for the first 14 days. Oral aripiprazole was available as rescue medication if necessary.	Participants at the investigator's discretion were eligible to continue to receive aripiprazole IM depot (400 or 300 mg) injection monthly in the Open-label Aripiprazole IM Depot Extension phase (C). Oral aripiprazole was available as rescue medication if necessary.
All-Cause Mortality
	Oral Aripiprazole (Phase A)	Aripiprazole IM Depot (Phase B)	Aripiprazole IM Depot (Phase C)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Oral Aripiprazole (Phase A)	Aripiprazole IM Depot (Phase B)	Aripiprazole IM Depot (Phase C)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Hepatobiliary disorders
Drug-induced liver injury †	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Psychiatric disorders
Schizophrenia †	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Oral Aripiprazole (Phase A)	Aripiprazole IM Depot (Phase B)	Aripiprazole IM Depot (Phase C)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/19 (21.05%)	10/19 (52.63%)	1/3 (33.33%)
Cardiac disorders
Palpitations	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Gastrointestinal disorders
Flatulence	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
General disorders
Fatigue	1/19 (5.26%)	2/19 (10.53%)	0/3 (0.00%)
Irritability	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Infections and infestations
Bronchitis	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Investigations
Alanine aminotransferase increased	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Aspartate aminotransferase increased	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Blood creatine phosphokinase increased	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Blood glucose increased	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Blood triglycerides increased	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Gamma-glutamyltransferase increased	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Weight decreased	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Metabolism and nutrition disorders
Diabetes mellitus	0/19 (0.00%)	1/19 (5.26%)	1/3 (33.33%)
Musculoskeletal and connective tissue disorders
Back pain	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Musculoskeletal pain	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)
Nervous system disorders
Somnolence	1/19 (5.26%)	1/19 (5.26%)	0/3 (0.00%)
Psychiatric disorders
Insomnia	3/19 (15.79%)	3/19 (15.79%)	0/3 (0.00%)
Psychotic disorder	0/19 (0.00%)	1/19 (5.26%)	0/3 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Medical Affairs
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Phone: 800-562-3974

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT01509053 History of Changes
• Other Study ID Numbers: 31-11-284
• First Submitted: December 13, 2011
• First Posted: January 12, 2012
• Results First Submitted: November 26, 2013
• Results First Posted: January 16, 2014
• Last Update Posted: March 4, 2015