Trial Outcomes & Findings for Switching to Iloperidone From Other Antipsychotics in Schizophrenia (NCT NCT01207414)

NCT ID: NCT01207414

Last Updated: 2013-03-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

501 participants

Primary outcome timeframe

Week 12

Results posted on

2013-03-15

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	241	260
Overall Study Safety Population: Received Study Drug	240	260
Overall Study COMPLETED	168	178
Overall Study NOT COMPLETED	73	82

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	25	39
Overall Study Abnormal test procedure results	0	1
Overall Study Unsatisfactory therapeutic effect	5	4
Overall Study Patient withdrew consent	14	11
Overall Study Lost to Follow-up	15	17
Overall Study Administrative problems	1	1
Overall Study Protocol deviation	12	9
Overall Study Randomized in error	1	0

Baseline Characteristics

Switching to Iloperidone From Other Antipsychotics in Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Iloperidone Gradual Switch n=240 Participants 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.	Iloperidone Immediate Switch n=260 Participants 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 n=500 Participants Total of all reporting groups
Age Continuous	42.3 years STANDARD_DEVIATION 10.98 • n=99 Participants	44.2 years STANDARD_DEVIATION 10.92 • n=107 Participants	43.3 years STANDARD_DEVIATION 10.98 • n=206 Participants
Sex: Female, Male Female	70 Participants n=99 Participants	95 Participants n=107 Participants	165 Participants n=206 Participants
Sex: Female, Male Male	170 Participants n=99 Participants	165 Participants n=107 Participants	335 Participants n=206 Participants

PRIMARY outcome

Timeframe: Week 12

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

Outcome measures

Outcome measures
Measure	Iloperidone Gradual Switch n=235 Participants 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.	Iloperidone Immediate Switch n=256 Participants 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.
Integrated Clinical Global Impression of Change (I-CGI-C) at Week 12	2.826 Score on a scale Standard Deviation 1.1244	2.824 Score on a scale Standard Deviation 1.3300

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Outcome measures
Measure	Iloperidone Gradual Switch n=214 Participants 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.	Iloperidone Immediate Switch n=233 Participants 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.
Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) at Week 12 Change from baseline 3 cohorts combined	14.1 Score on a scale Standard Deviation 29.56	12.7 Score on a scale Standard Deviation 27.89
Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) at Week 12 Change from baseline risperidone cohort (n=75,85)	14.4 Score on a scale Standard Deviation 27.0	16.6 Score on a scale Standard Deviation 29.65
Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) at Week 12 Change from baseline olanzapine cohort (n=70,67)	13.3 Score on a scale Standard Deviation 28.17	9.9 Score on a scale Standard Deviation 28.60
Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) at Week 12 Change from baseline aripiprazole cohort (n=69,81)	14.8 Score on a scale Standard Deviation 33.72	11.0 Score on a scale Standard Deviation 25.12

SECONDARY outcome

Timeframe: 12 Weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Iloperidone Gradual Switch n=240 Participants 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.	Iloperidone Immediate Switch n=260 Participants 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.
Number of Participants With Adverse Events, Serious Adverse Events or Death Adverse Events	196 Participants	207 Participants
Number of Participants With Adverse Events, Serious Adverse Events or Death Serious Adverse Events	8 Participants	7 Participants
Number of Participants With Adverse Events, Serious Adverse Events or Death Death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Outcome measures
Measure	Iloperidone Gradual Switch n=235 Participants 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.	Iloperidone Immediate Switch n=256 Participants 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.
Change From Baseline in the Efficacy Clinical Global Impression of Severity (E-CGI-S) at Week 12 Change from baseline 3 cohorts combined	-0.8 Score on a scale Standard Deviation 0.89	-0.8 Score on a scale Standard Deviation 0.89
Change From Baseline in the Efficacy Clinical Global Impression of Severity (E-CGI-S) at Week 12 Change from baseline risperidone cohort (n=81,92)	-0.9 Score on a scale Standard Deviation 0.82	-0.9 Score on a scale Standard Deviation 0.85
Change From Baseline in the Efficacy Clinical Global Impression of Severity (E-CGI-S) at Week 12 Change from baseline olanzapine cohort (n=77,74)	-0.8 Score on a scale Standard Deviation 0.96	-0.6 Score on a scale Standard Deviation 0.88
Change From Baseline in the Efficacy Clinical Global Impression of Severity (E-CGI-S) at Week 12 Change from baseline aripiprazole cohort (n=77,90)	-0.8 Score on a scale Standard Deviation 0.89	-0.9 Score on a scale Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Outcome measures
Measure	Iloperidone Gradual Switch n=235 Participants 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.	Iloperidone Immediate Switch n=256 Participants 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.
Change From Baseline in the Safety and Tolerability Clinical Global Impression of Severity (ST-CGI-S) at Week 12 Change from baseline risperidone cohort (n=81,92)	-1.1 Score on a scale Standard Deviation 1.27	-0.9 Score on a scale Standard Deviation 1.49
Change From Baseline in the Safety and Tolerability Clinical Global Impression of Severity (ST-CGI-S) at Week 12 Change from baseline olanzapine cohort (n=77,74)	-0.9 Score on a scale Standard Deviation 1.20	-0.9 Score on a scale Standard Deviation 1.36
Change From Baseline in the Safety and Tolerability Clinical Global Impression of Severity (ST-CGI-S) at Week 12 Change from baseline 3 cohorts combined	-0.9 Score on a scale Standard Deviation 1.29	-0.8 Score on a scale Standard Deviation 1.45
Change From Baseline in the Safety and Tolerability Clinical Global Impression of Severity (ST-CGI-S) at Week 12 Change from baseline aripiprazole cohort (n=77,90)	-0.8 Score on a scale Standard Deviation 1.39	-0.4 Score on a scale Standard Deviation 1.45

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Iloperidone Gradual Switch n=235 Participants 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.	Iloperidone Immediate Switch n=256 Participants 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.
Change From Baseline in Integrated Clinical Global Impression of Severity (I-CGI-S) at Week 12 Change from baseline 3 cohorts combined	-0.9 Score on a scale Standard Deviation 0.95	-0.9 Score on a scale Standard Deviation 0.97
Change From Baseline in Integrated Clinical Global Impression of Severity (I-CGI-S) at Week 12 Change from baseline aripiprazole cohort (n=77,80)	-1.0 Score on a scale Standard Deviation 1.04	-0.9 Score on a scale Standard Deviation 1.04
Change From Baseline in Integrated Clinical Global Impression of Severity (I-CGI-S) at Week 12 Change from baseline risperidone cohort (n=81,92)	-0.9 Score on a scale Standard Deviation 0.85	-1.0 Score on a scale Standard Deviation 0.89
Change From Baseline in Integrated Clinical Global Impression of Severity (I-CGI-S) at Week 12 Change from baseline olanzapine cohort (n=77,74)	-0.8 Score on a scale Standard Deviation 0.96	-0.7 Score on a scale Standard Deviation 0.98

Adverse Events

Iloperidone Gradual Switch

Serious events: 8 serious events

Other events: 148 other events

Deaths: 0 deaths

Iloperidone Immediate Switch

Serious events: 7 serious events

Other events: 155 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Iloperidone Gradual Switch n=240 participants at risk 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.	Iloperidone Immediate Switch n=260 participants at risk 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.
Gastrointestinal disorders Dry mouth	17.9% 43/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	20.8% 54/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	5.4% 13/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	6.5% 17/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
General disorders Fatigue	8.8% 21/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	7.7% 20/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Investigations Weight increased	12.1% 29/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	7.7% 20/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Increased appetite	5.4% 13/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	5.4% 14/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Nervous system disorders Dizziness	17.5% 42/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	22.3% 58/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	7.1% 17/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	7.3% 19/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Nervous system disorders Sedation	9.2% 22/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	8.5% 22/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Nervous system disorders Somnolence	14.2% 34/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	9.6% 25/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	4.6% 11/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	6.9% 18/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	8.3% 20/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	9.6% 25/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.8% 14/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	4.2% 11/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Iloperidone Gradual Switch n=240 participants at risk 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.	Iloperidone Immediate Switch n=260 participants at risk 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.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.42% 1/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.00% 0/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Oesophageal perforation	0.00% 0/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.38% 1/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
General disorders Concomitant disease progression	0.42% 1/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.00% 0/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Infections and infestations Appendicitis	0.42% 1/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.00% 0/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.00% 0/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.38% 1/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Overdose	0.42% 1/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.00% 0/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.42% 1/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.00% 0/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Nervous system disorders Syncope	0.42% 1/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.38% 1/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Psychiatric disorders Depression	0.42% 1/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.00% 0/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Psychiatric disorders Schizophrenia	0.42% 1/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.77% 2/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.38% 1/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.38% 1/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.38% 1/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.42% 1/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.00% 0/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.
Social circumstances Social stay hospitalisation	0.42% 1/240 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.	0.00% 0/260 • 12 weeks Safety Set includes all randomized participants who received at least one dose of study drug.