i-FANS: Switching to Iloperidone From Other Antipsychotics in Schizophrenia

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01207414
• Collaborator: (none)
• Enrollment: 501
• Locations: 59
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Evaluate the clinical outcome of two switching strategies to iloperidone treatment in adult subjects with schizophrenia who require a change in their current antipsychotic treatment of risperidone, olanzapine, or aripiprazole due to suboptimal efficacy and/or safety/tolerability reasons.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: iloperidone	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 501 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 12-week, Randomized, Multi-center, Open-Label, Iloperidone, (12-24 mg/Day), Flexible Dose Study Assessing Efficacy, Safety and Tolerability of Two Switch Approaches in Schizophrenia Patients Currently Receiving Risperidone, Olanzapine or Aripiprazole
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: iloperidone gradual switch Participants taking risperidone, olanzapine or aripiprazole gradually decreased the dose they were taking: 50% of original dose on Day 1, 25% of original dose after the first week and the total discontinuation of the drug after the second week. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Drug: iloperidone; Iloperidone tablets supplied at doses of 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 mg to achieve a target dose of 12-24 mg/day for 12 weeks.; Other Names: Fanapt™
Experimental: iloperidone immediate switch Participants taking risperidone, olanzapine or aripiprazole discontinued the drug immediately. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Drug: iloperidone; Iloperidone tablets supplied at doses of 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 mg to achieve a target dose of 12-24 mg/day for 12 weeks.; Other Names: Fanapt™

Outcome Measures

Primary Outcome Measures

1. Integrated Clinical Global Impression of Change (I-CGI-C) at Week 12 [Week 12]

   The I-CGI-C at Week 12 was the overall impression of medically qualified raters using three separate Clinical Global Impression of Change scales: efficacy (E-CGI-C); safety and tolerability (ST-CGI-S); and overall severity (I-CGI-S) combined for a total score. The I-CGI-C scale ranged from 1 to 7 with lower scores indicating improvement (1=very much improved, 2=much improved, 3=minimally improved), higher scores indicating worsening (5=minimally worse, 6= much worse, 7=very much worse), and a score of 4 indicating no change.

Secondary Outcome Measures

1. Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) at Week 12 [Baseline, Week 12]

   The TSQM consisted of 14 questions about the patient's satisfaction with the drug in 4 domains: Effectiveness [3 questions scored as 1(extremely dissatisfied) to 7(extremely satisfied)], Side Effects [question 4 scored as 0(no) or 1(yes);question 5 scored as 1(extremely bothersome) to 5(not at all bothersome);questions 6 - 8 scored as 1(a great deal) to 5(not at all)], Convenience [questions 9 and 10 scored as 1(extremely difficult) to 7 (extremely easy);question 11 scored as 1(extremely inconvenient) to 5 (extremely convenient)] and Global Satisfaction [question 12 scored as 1(not at all confident) to 7(extremely confident);question 13 scored as 1(not at all certain) to 5(extremely certain);question 14 scored as 1(extremely dissatisfied) to 5(extremely satisfied)]. The scores of each of the domains were added together and an algorithm used to create a score of 0 to 100. Higher scores for each domain indicate a better outcome. A positive change from baseline indicates improvement.

2. Number of Participants With Adverse Events, Serious Adverse Events or Death [12 Weeks]

   Adverse event are defined as any unfavorable and unintended diagnosis, symptoms, sign (including an abnormal lab finding), syndrome or disease which either occurs during the study, having been absent at baseline, or if present at baseline appear to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization , cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards. Additional information about adverse events can be found in the Adverse Event section.

3. Change From Baseline in the Efficacy Clinical Global Impression of Severity (E-CGI-S) at Week 12 [Baseline, Week 12]

   Medically qualified raters use the E-CGI-S scale at Baseline and Week 12 to assess the effectiveness of treatment by examining changes in positive symptoms [hallucinations (false perceptions), delusions (false beliefs), paranoia (unfounded distrust), conceptual disorganization (loosening of associations), or hostility], negative symptoms [apathy (lack of interest), avolition (lack of motivation), alogia (poverty of speech), and anhedonia (absence of pleasure)] and cognitive symptoms [concentration difficulties, difficulties with executive function (integrative reasoning), and illogical thinking] in the previous 7 days on a scale of 1 to 7 (1=normal, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill or 7=among the most extremely ill). A negative change from baseline indicates improvement.

4. Change From Baseline in the Safety and Tolerability Clinical Global Impression of Severity (ST-CGI-S) at Week 12 [Baseline, Week 12]

   Medically qualified raters used the ST-CGI-S at Baseline and Week 12 to evaluate safety and tolerability in the previous 7 days on a scale of 1 to 7 (1=Normal-no symptoms, 2=borderline severity, 3=mild impairment, 4=moderate, 5=marked, 6=severe, 7=among the most severe.) A negative change from baseline indicates improvement.

5. Change From Baseline in Integrated Clinical Global Impression of Severity (I-CGI-S) at Week 12 [Baseline, Week 12]

   I-CGI-S incorporated the overall, combined impression of illness severity based upon the E-CGI-S and ST-CGI-S. Medically qualified raters evaluated the patient's illness in the previous 7 days at Baseline and Week 12 on a scale of 1 to 7 (1=normal not at all ill, 2=borderline mental illness or impairment, 3=mildly ill or impaired, 4=moderately ill or impaired, 5=marked ill or impaired, 6= severely ill or impaired or 7=among the most extremely ill patients. A negative change from baseline indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or females, 18 to 64 years of age, inclusive

• DSM-IV diagnosis of schizophrenia

• Patients currently on an optimal in-label dose of one of the following permitted antipsychotic treatments for at least 30 days: risperidone, olanzapine, or aripiprazole

• Efficacy Clinical Global Impression of Severity (E-CGI-S) of 4 or 5 or

• Not tolerating one of the permitted treatments and exhibits one of the allowable side-effects

Exclusion Criteria:

• Any other current Axis I disorder other than schizophrenia which is the focus of treatment;

• Acutely psychotic or patient's symptom severity requires hospitalization

• Patient with significant cardiovascular illness (myocardial infarction, cardiac arrhythmia)

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Psychiatry Pharmaceutical Studies, Inc.	Birmingham	Alabama	United States	35226
2	Comprehensive Neuroscience	Cerritos	California	United States	90703
3	ATP Clinical Research Center, Inc.	Costa Mesa	California	United States	92626
4	Collaborative Neuroscience Network	Garden Grove	California	United States	92845
5	Apostle Clinical Trials, Inc.	Long Beach	California	United States	90813
6	Pacific Health Systems	National City	California	United States	91950
7	Pacific Research Partners	Oakland	California	United States	94612
8	Excell Research, Inc.	Oceanside	California	United States	92056
9	University of California, Irvine	Orange	California	United States	92868
10	CNRI San Diego	San Diego	California	United States	92102
11	Affiliated Research Institute	San Diego	California	United States	92108
12	Artemis Institute for Clinical Research	San Diego	California	United States	92108
13	Neuropsychiatric Research Center of Orange County	Santa Ana	California	United States	92701
14	Viking Clinical Research	Temecula	California	United States	92591
15	Collaborative Neuroscience	Torrance	California	United States	90502
16	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06052
17	Comprenhensive Neuroscience	Washington	District of Columbia	United States	20016
18	Amit K. Vijapura MD & Associates	Jacksonville	Florida	United States	32256
19	Scientific Clinical Research	North Miami	Florida	United States	33161
20	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30308
21	Comprehensive Neuroscience	Atlanta	Georgia	United States	30328
22	Northwest Behavioral Research Center	Marietta	Georgia	United States	30060
23	Carman Research	Smyrna	Georgia	United States	30080
24	Institute for Behavioral Medicine	Smyrna	Georgia	United States	30080
25	Alexian Brothers Center for Mental Health	Arlington Heights	Illinois	United States	60005
26	Rush University Medical Center, Treatment Research Center	Chicago	Illinois	United States	60612
27	University of Illinois at Chicago	Chicago	Illinois	United States	60612
28	AMR - Baber Research, Inc.	Naperville	Illinois	United States	60563
29	Midwest Center for Neurobehavioral Medicine	Oakbrook Terrace	Illinois	United States	60181
30	Louisiana Clinical Research	Shreveport	Louisiana	United States	71115
31	Neurobehavioral Medicine Group, Clinical Trials Division	Bloomfield Hills	Michigan	United States	48302
32	Rochester Center for Behavioral Medicine	Rochester Hills	Michigan	United States	48307
33	Precise Research Centers	Flowood	Mississippi	United States	39232
34	St. Charles Psychiatric Associates - Midwest Research Group	Saint Charles	Missouri	United States	63301
35	Center for Emotional Fitness	Cherry Hill	New Jersey	United States	08002
36	CRI World Wide Clinical Research Company	Willingboro	New Jersey	United States	08046
37	Albuquerque Neuroscience	Albuquerque	New Mexico	United States	87109
38	Neurobehavioral Research	Cedarhurst	New York	United States	11516
39	Comprehensive Neuroscience	Fresh Meadows	New York	United States	11366
40	Division of Psychiatry Research - Zucker Hills Hospital	Glen Oaks	New York	United States	11004
41	Finger Lakes Clinical Research	Rochester	New York	United States	14618
42	Behavioral Medical Research	Staten Island	New York	United States	10305
43	Richmond Behavioral Associates	Staten Island	New York	United States	10312
44	North Coast Clinical Trials	Beachwood	Ohio	United States	44122
45	Neurobehavioral Clinical Research	Canton	Ohio	United States	44718
46	IPS Research Company	Oklahoma City	Oklahoma	United States	73103
47	SP Research, PLLC	Oklahoma City	Oklahoma	United States	73112
48	Belmont Center for Comprehensive Treatment	Philadelphia	Pennsylvania	United States	19131
49	CRI Worldwide, LLC - Kirkbride Division	Philadelphia	Pennsylvania	United States	19139
50	Carolina Clinical Trials	Charleston	South Carolina	United States	29407
51	Community Clinical Research, Inc.	Austin	Texas	United States	78754
52	KRK Medical Research	Dallas	Texas	United States	75230
53	FutureSearch Trials	Dallas	Texas	United States	75231
54	InSite Clinical Research	Desoto	Texas	United States	75115
55	Bayou City Research Limited	Houston	Texas	United States	77007
56	Claghorn-Lesem Research Clinic, Inc	Houston	Texas	United States	77008
57	Mary Ann Knesevich, MD, PA	Irving	Texas	United States	75062
58	InSite Clinical Research	Plano	Texas	United States	75074
59	Frontier Institute	Spokane	Washington	United States	99204

Sponsors and Collaborators

• Novartis

Investigators

• Study Director: Marla Hochfeld, MD, MD, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT01207414
• Other Study ID Numbers: CILO522DUS01
• First Posted: Sep 22, 2010
• Last Update Posted: Mar 15, 2013
• Last Verified: Feb 1, 2013

• Keywords provided by Novartis: Schizophrenia; iloperidone; switch; gradual switch; immediate switch
• Additional relevant MeSH terms: Schizophrenia; Iloperidone

Study Results

Participant Flow

Pre-assignment Detail	500 participants taking antipsychotic drugs: 175 participants in the risperidone cohort, 155 participants in the olanzapine cohort and 170 participants in the aripiprazole cohort were randomized and received study drug in one of two iloperidone treatment arms: gradual switch or immediate switch. 1 randomized participant did not receive study drug.

Arm/Group Title	Iloperidone Gradual Switch	Iloperidone Immediate Switch
Arm/Group Description	Participants taking risperidone, olanzapine or aripiprazole gradually decreased the dose they were taking: 50% of original dose on Day 1, 25% of original dose after the first week and the total discontinuation of the drug after the second week. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Participants taking risperidone, olanzapine or aripiprazole discontinued the drug immediately. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.
Period Title: Overall Study
STARTED	241	260
Safety Population: Received Study Drug	240	260
COMPLETED	168	178
NOT COMPLETED	73	82

Baseline Characteristics

Arm/Group Title	Iloperidone Gradual Switch	Iloperidone Immediate Switch	Total
Arm/Group Description	Participants taking risperidone, olanzapine or aripiprazole gradually decreased the dose they were taking: 50% of original dose on Day 1, 25% of original dose after the first week and the total discontinuation of the drug after the second week. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Participants taking risperidone, olanzapine or aripiprazole discontinued the drug immediately. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Total of all reporting groups
Overall Participants	240	260	500
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.3 (10.98)	44.2 (10.92)	43.3 (10.98)
Sex: Female, Male (Count of Participants)
Female	70 29.2%	95 36.5%	165 33%
Male	170 70.8%	165 63.5%	335 67%

Outcome Measures

1. Primary Outcome

Title	Integrated Clinical Global Impression of Change (I-CGI-C) at Week 12
Description	The I-CGI-C at Week 12 was the overall impression of medically qualified raters using three separate Clinical Global Impression of Change scales: efficacy (E-CGI-C); safety and tolerability (ST-CGI-S); and overall severity (I-CGI-S) combined for a total score. The I-CGI-C scale ranged from 1 to 7 with lower scores indicating improvement (1=very much improved, 2=much improved, 3=minimally improved), higher scores indicating worsening (5=minimally worse, 6= much worse, 7=very much worse), and a score of 4 indicating no change.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set (three cohorts combined: risperidone, olanzapine or aripiprazole) with data available for analyses.

Arm/Group Title	Iloperidone Gradual Switch	Iloperidone Immediate Switch
Arm/Group Description	Participants taking risperidone, olanzapine or aripiprazole gradually decreased the dose they were taking: 50% of original dose on Day 1, 25% of original dose after the first week and the total discontinuation of the drug after the second week. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Participants taking risperidone, olanzapine or aripiprazole discontinued the drug immediately. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.
Measure Participants	235	256
Mean (Standard Deviation) [Score on a scale]	2.826 (1.1244)	2.824 (1.3300)

2. Secondary Outcome

Title	Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) at Week 12
Description	The TSQM consisted of 14 questions about the patient's satisfaction with the drug in 4 domains: Effectiveness [3 questions scored as 1(extremely dissatisfied) to 7(extremely satisfied)], Side Effects [question 4 scored as 0(no) or 1(yes);question 5 scored as 1(extremely bothersome) to 5(not at all bothersome);questions 6 - 8 scored as 1(a great deal) to 5(not at all)], Convenience [questions 9 and 10 scored as 1(extremely difficult) to 7 (extremely easy);question 11 scored as 1(extremely inconvenient) to 5 (extremely convenient)] and Global Satisfaction [question 12 scored as 1(not at all confident) to 7(extremely confident);question 13 scored as 1(not at all certain) to 5(extremely certain);question 14 scored as 1(extremely dissatisfied) to 5(extremely satisfied)]. The scores of each of the domains were added together and an algorithm used to create a score of 0 to 100. Higher scores for each domain indicate a better outcome. A positive change from baseline indicates improvement.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set with data available for analyses.

Arm/Group Title	Iloperidone Gradual Switch	Iloperidone Immediate Switch
Arm/Group Description	Participants taking risperidone, olanzapine or aripiprazole gradually decreased the dose they were taking: 50% of original dose on Day 1, 25% of original dose after the first week and the total discontinuation of the drug after the second week. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Participants taking risperidone, olanzapine or aripiprazole discontinued the drug immediately. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.
Measure Participants	214	233
Change from baseline 3 cohorts combined	14.1 (29.56)	12.7 (27.89)
Change from baseline risperidone cohort (n=75,85)	14.4 (27.0)	16.6 (29.65)
Change from baseline olanzapine cohort (n=70,67)	13.3 (28.17)	9.9 (28.60)
Change from baseline aripiprazole cohort (n=69,81)	14.8 (33.72)	11.0 (25.12)

3. Secondary Outcome

Title	Number of Participants With Adverse Events, Serious Adverse Events or Death
Description	Adverse event are defined as any unfavorable and unintended diagnosis, symptoms, sign (including an abnormal lab finding), syndrome or disease which either occurs during the study, having been absent at baseline, or if present at baseline appear to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization , cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards. Additional information about adverse events can be found in the Adverse Event section.
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Participants from the Safety Analysis Set- all randomized participants who received study drug (three cohorts combined: risperidone, olanzapine or aripiprazole) with data available for analyses.

Arm/Group Title	Iloperidone Gradual Switch	Iloperidone Immediate Switch
Arm/Group Description	Participants taking risperidone, olanzapine or aripiprazole gradually decreased the dose they were taking: 50% of original dose on Day 1, 25% of original dose after the first week and the total discontinuation of the drug after the second week. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Participants taking risperidone, olanzapine or aripiprazole discontinued the drug immediately. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.
Measure Participants	240	260
Serious Adverse Events	8 3.3%	7 2.7%
Adverse Events	196 81.7%	207 79.6%
Death	0 0%	0 0%

4. Secondary Outcome

Title	Change From Baseline in the Efficacy Clinical Global Impression of Severity (E-CGI-S) at Week 12
Description	Medically qualified raters use the E-CGI-S scale at Baseline and Week 12 to assess the effectiveness of treatment by examining changes in positive symptoms [hallucinations (false perceptions), delusions (false beliefs), paranoia (unfounded distrust), conceptual disorganization (loosening of associations), or hostility], negative symptoms [apathy (lack of interest), avolition (lack of motivation), alogia (poverty of speech), and anhedonia (absence of pleasure)] and cognitive symptoms [concentration difficulties, difficulties with executive function (integrative reasoning), and illogical thinking] in the previous 7 days on a scale of 1 to 7 (1=normal, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill or 7=among the most extremely ill). A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set with data available for analyses.

Arm/Group Title	Iloperidone Gradual Switch	Iloperidone Immediate Switch
Arm/Group Description	Participants taking risperidone, olanzapine or aripiprazole gradually decreased the dose they were taking: 50% of original dose on Day 1, 25% of original dose after the first week and the total discontinuation of the drug after the second week. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Participants taking risperidone, olanzapine or aripiprazole discontinued the drug immediately. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.
Measure Participants	235	256
Change from baseline 3 cohorts combined	-0.8 (0.89)	-0.8 (0.89)
Change from baseline risperidone cohort (n=81,92)	-0.9 (0.82)	-0.9 (0.85)
Change from baseline olanzapine cohort (n=77,74)	-0.8 (0.96)	-0.6 (0.88)
Change from baseline aripiprazole cohort (n=77,90)	-0.8 (0.89)	-0.9 (0.92)

5. Secondary Outcome

Title	Change From Baseline in the Safety and Tolerability Clinical Global Impression of Severity (ST-CGI-S) at Week 12
Description	Medically qualified raters used the ST-CGI-S at Baseline and Week 12 to evaluate safety and tolerability in the previous 7 days on a scale of 1 to 7 (1=Normal-no symptoms, 2=borderline severity, 3=mild impairment, 4=moderate, 5=marked, 6=severe, 7=among the most severe.) A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set with data available for analyses.

Arm/Group Title	Iloperidone Gradual Switch	Iloperidone Immediate Switch
Arm/Group Description	Participants taking risperidone, olanzapine or aripiprazole gradually decreased the dose they were taking: 50% of original dose on Day 1, 25% of original dose after the first week and the total discontinuation of the drug after the second week. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Participants taking risperidone, olanzapine or aripiprazole discontinued the drug immediately. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.
Measure Participants	235	256
Change from baseline 3 cohorts combined	-0.9 (1.29)	-0.8 (1.45)
Change from baseline risperidone cohort (n=81,92)	-1.1 (1.27)	-0.9 (1.49)
Change from baseline olanzapine cohort (n=77,74)	-0.9 (1.20)	-0.9 (1.36)
Change from baseline aripiprazole cohort (n=77,90)	-0.8 (1.39)	-0.4 (1.45)

6. Secondary Outcome

Title	Change From Baseline in Integrated Clinical Global Impression of Severity (I-CGI-S) at Week 12
Description	I-CGI-S incorporated the overall, combined impression of illness severity based upon the E-CGI-S and ST-CGI-S. Medically qualified raters evaluated the patient's illness in the previous 7 days at Baseline and Week 12 on a scale of 1 to 7 (1=normal not at all ill, 2=borderline mental illness or impairment, 3=mildly ill or impaired, 4=moderately ill or impaired, 5=marked ill or impaired, 6= severely ill or impaired or 7=among the most extremely ill patients. A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Iloperidone Gradual Switch	Iloperidone Immediate Switch
Arm/Group Description	Participants taking risperidone, olanzapine or aripiprazole gradually decreased the dose they were taking: 50% of original dose on Day 1, 25% of original dose after the first week and the total discontinuation of the drug after the second week. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.	Participants taking risperidone, olanzapine or aripiprazole discontinued the drug immediately. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.
Measure Participants	235	256
Change from baseline 3 cohorts combined	-0.9 (0.95)	-0.9 (0.97)
Change from baseline risperidone cohort (n=81,92)	-0.9 (0.85)	-1.0 (0.89)
Change from baseline olanzapine cohort (n=77,74)	-0.8 (0.96)	-0.7 (0.98)
Change from baseline aripiprazole cohort (n=77,80)	-1.0 (1.04)	-0.9 (1.04)

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	Safety Set includes all randomized participants who received at least one dose of study drug.
Arm/Group Title	Iloperidone Gradual Switch		Iloperidone Immediate Switch
Arm/Group Description	Participants taking risperidone, olanzapine or aripiprazole gradually decreased the dose they were taking: 50% of original dose on Day 1, 25% of original dose after the first week and the total discontinuation of the drug after the second week. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.		Participants taking risperidone, olanzapine or aripiprazole discontinued the drug immediately. On Day 1 participants began taking iloperidone orally twice a day (bid) in the morning and in the evening beginning at a dose of 1 mg and increasing to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg bid on consecutive days over a 7-day period to achieve a total dose of 12-24 mg/day for 12 weeks.
All Cause Mortality
	Iloperidone Gradual Switch		Iloperidone Immediate Switch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Iloperidone Gradual Switch		Iloperidone Immediate Switch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/240 (3.3%)		7/260 (2.7%)
Gastrointestinal disorders
Lower gastrointestinal haemorrhage	1/240 (0.4%)		0/260 (0%)
Oesophageal perforation	0/240 (0%)		1/260 (0.4%)
General disorders
Concomitant disease progression	1/240 (0.4%)		0/260 (0%)
Infections and infestations
Appendicitis	1/240 (0.4%)		0/260 (0%)
Pneumonia	0/240 (0%)		1/260 (0.4%)
Injury, poisoning and procedural complications
Overdose	1/240 (0.4%)		0/260 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/240 (0.4%)		0/260 (0%)
Nervous system disorders
Syncope	1/240 (0.4%)		1/260 (0.4%)
Psychiatric disorders
Depression	1/240 (0.4%)		0/260 (0%)
Schizophrenia	1/240 (0.4%)		2/260 (0.8%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/240 (0%)		1/260 (0.4%)
Dyspnoea	0/240 (0%)		1/260 (0.4%)
Pulmonary embolism	0/240 (0%)		1/260 (0.4%)
Respiratory failure	1/240 (0.4%)		0/260 (0%)
Social circumstances
Social stay hospitalisation	1/240 (0.4%)		0/260 (0%)
Other (Not Including Serious) Adverse Events
	Iloperidone Gradual Switch		Iloperidone Immediate Switch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	148/240 (61.7%)		155/260 (59.6%)
Gastrointestinal disorders
Dry mouth	43/240 (17.9%)		54/260 (20.8%)
Nausea	13/240 (5.4%)		17/260 (6.5%)
General disorders
Fatigue	21/240 (8.8%)		20/260 (7.7%)
Investigations
Weight increased	29/240 (12.1%)		20/260 (7.7%)
Metabolism and nutrition disorders
Increased appetite	13/240 (5.4%)		14/260 (5.4%)
Nervous system disorders
Dizziness	42/240 (17.5%)		58/260 (22.3%)
Headache	17/240 (7.1%)		19/260 (7.3%)
Sedation	22/240 (9.2%)		22/260 (8.5%)
Somnolence	34/240 (14.2%)		25/260 (9.6%)
Psychiatric disorders
Anxiety	11/240 (4.6%)		18/260 (6.9%)
Insomnia	20/240 (8.3%)		25/260 (9.6%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	14/240 (5.8%)		11/260 (4.2%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.