Trial Outcomes & Findings for Prevention of Relapse With Injectable Paliperidone Palmitate Versus Oral Antipsychotics (NCT NCT01081769)

Last Updated: 2015-02-18

Results Overview

Number of days from baseline (day 1 of core phase) to relapse as evaluated according the Csernansky criteria. A patient was considered to have relapsed if they met one or more of the following criteria: (1) psychiatric hospitalization; (2) an increase in the level of psychiatric care and an increase of 25 percent (%) from baseline in the Positive And Negative Syndrome Score (PANSS) total score (or an increase of 10 points if the baseline score was 40 or less); (3) deliberate self-injury; (4) suicidal or homicidal ideation that was clinically significant in the investigator's judgment; (5) violent behavior resulting in clinically significant injury to another person or property damage; (6) substantial clinical deterioration, defined as a change score of 6 ("much worse") or 7 ("very much worse") on the Clinical Global Impressions Scale (CGI-C); and/or (7) the required dose of the antipsychotic exceeds the maximum approved dose.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

769 participants

Primary outcome timeframe

from baseline (Day 1 of core phase) up to maximally 24 months.

Results posted on

2015-02-18

Participant Flow

After randomization patients enrolled in a 2-week oral treatment phase and were considered part of the whole Intent-to-Treat population (Whole ITT). Five patients did not receive study medication after randomization and were excluded from the whole ITT. Only responders were considered for continuation in the Core treatment phase (Core ITT).

Participant milestones

Participant milestones
Measure	Paliperidone Palmitate 2 weeks oral paliperidone treatment followed by intramuscular injection with 150 mg paliperidone palmitate equivalent on Day 1 of the core treatment phase, 100 mg equivalent on Day 8, 75 mg equivalent on Day 38 and flexible dosing with 25, 50, 75, 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics Oral antipsychotics daily treatment according to local label for maximally 24 months
Whole Intent-to-Treat STARTED	376	388
Whole Intent-to-Treat COMPLETED	352	363
Whole Intent-to-Treat NOT COMPLETED	24	25
CORE Intent-To-Treat STARTED	352	363
CORE Intent-To-Treat COMPLETED	272	266
CORE Intent-To-Treat NOT COMPLETED	80	97

Reasons for withdrawal

Reasons for withdrawal
Measure	Paliperidone Palmitate 2 weeks oral paliperidone treatment followed by intramuscular injection with 150 mg paliperidone palmitate equivalent on Day 1 of the core treatment phase, 100 mg equivalent on Day 8, 75 mg equivalent on Day 38 and flexible dosing with 25, 50, 75, 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics Oral antipsychotics daily treatment according to local label for maximally 24 months
Whole Intent-to-Treat Missing Responder Assessment	10	12
Whole Intent-to-Treat Stopped; non-responder after 2 weeks	6	6
Whole Intent-to-Treat Deviation; non-responder after 2 weeks	6	7
Whole Intent-to-Treat Responder after 2 weeks, but stopped	2	0
CORE Intent-To-Treat Adverse Event	14	11
CORE Intent-To-Treat Death	1	1
CORE Intent-To-Treat Lack of Efficacy	2	6
CORE Intent-To-Treat Lost to Follow-up	4	5
CORE Intent-To-Treat Pregnancy	1	0
CORE Intent-To-Treat Withdrawal by Subject	52	60
CORE Intent-To-Treat Noncompliance With Study Drug	0	5
CORE Intent-To-Treat Other	0	1
CORE Intent-To-Treat Ineligibility	3	4
CORE Intent-To-Treat Visit Schedule Issues	1	2
CORE Intent-To-Treat Patient Moved	2	2

Baseline Characteristics

Prevention of Relapse With Injectable Paliperidone Palmitate Versus Oral Antipsychotics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Paliperidone Palmitate n=376 Participants 2 weeks oral paliperidone treatment followed by intramuscular injection with 150 mg paliperidone palmitate equivalent on Day 1 of the core treatment phase, 100 mg equivalent on Day 8, 75 mg equivalent on Day 38 and flexible dosing with 25, 50, 75, 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=388 Participants Oral antipsychotics daily treatment according to local label for maximally 24 months	Total n=764 Participants Total of all reporting groups
Age, Continuous	32.5 years STANDARD_DEVIATION 10.73 • n=5 Participants	32.4 years STANDARD_DEVIATION 10 • n=7 Participants	32.5 years STANDARD_DEVIATION 10.36 • n=5 Participants
Sex: Female, Male Female	147 Participants n=5 Participants	171 Participants n=7 Participants	318 Participants n=5 Participants
Sex: Female, Male Male	229 Participants n=5 Participants	217 Participants n=7 Participants	446 Participants n=5 Participants
Region of Enrollment AUSTRIA	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment BELGIUM	7 participants n=5 Participants	5 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment BULGARIA	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment CROATIA	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment CZECH REPUBLIC	14 participants n=5 Participants	21 participants n=7 Participants	35 participants n=5 Participants
Region of Enrollment EGYPT	16 participants n=5 Participants	14 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment ESTONIA	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment FRANCE	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment GERMANY	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment HUNGARY	15 participants n=5 Participants	16 participants n=7 Participants	31 participants n=5 Participants
Region of Enrollment ISRAEL	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment ITALY	10 participants n=5 Participants	11 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment JORDAN	15 participants n=5 Participants	11 participants n=7 Participants	26 participants n=5 Participants
Region of Enrollment KOREA, REPUBLIC OF KOREA	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment LITHUANIA	13 participants n=5 Participants	14 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment POLAND	11 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment ROMANIA	13 participants n=5 Participants	14 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment RUSSIAN FEDERATION	90 participants n=5 Participants	90 participants n=7 Participants	180 participants n=5 Participants
Region of Enrollment SLOVAKIA	13 participants n=5 Participants	14 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment SOUTH AFRICA	26 participants n=5 Participants	24 participants n=7 Participants	50 participants n=5 Participants
Region of Enrollment SPAIN	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment TAIWAN, PROVINCE OF CHINA	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment TURKEY	11 participants n=5 Participants	9 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment UKRAINE	71 participants n=5 Participants	79 participants n=7 Participants	150 participants n=5 Participants

PRIMARY outcome

Timeframe: from baseline (Day 1 of core phase) up to maximally 24 months.

Population: all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Time to First Relapse Event	616 days Standard Error 10.9	603 days Standard Error 13.1

PRIMARY outcome

Timeframe: from baseline (Day 1 of core phase) up to maximally 24 months

Number of participants with a relapse event with relapses evaluated according the Csernansky criteria. A patient was considered to have relapsed if they met one or more of the following criteria: (1) psychiatric hospitalization; (2) an increase in the level of psychiatric care and an increase of 25% from baseline in the PANSS total score (or an increase of 10 points if the baseline score was 40 or less); (3) deliberate self-injury; (4) suicidal or homicidal ideation that was clinically significant in the investigator's judgment; (5) violent behavior resulting in clinically significant injury to another person or property damage; (6) substantial clinical deterioration, defined as a change score of 6 ("much worse") or 7 ("very much worse") on the Clinical Global Impressions Scale (CGI-C); and/or (7) the required dose of the antipsychotic exceeds the maximum approved dose.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Number of Participants With a Relapse Event No	300 number of participants	287 number of participants
Number of Participants With a Relapse Event Yes	52 number of participants	76 number of participants

SECONDARY outcome

Timeframe: from baseline (day 1 of core phase) up to maximally 24 months

The proportion of patients achieving a treatment response, defined as a ≥30% decrease (i.e., improvement) in Positive and Negative Syndrome Scale (PANSS) total score from baseline to endpoint. The PANSS is a 30-item scale (Range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate increased severity of schizophrenia symptoms.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Percentage of Treatment Responders	75.6 percentage of participants Interval 70.8 to 79.8	69.4 percentage of participants Interval 64.5 to 73.9

SECONDARY outcome

Timeframe: Baseline, day 8, month 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, 24

Change from baseline in the PANSS: The PANSS is a 30-item scale (Range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Change From Baseline in PANSS Total Score change from baseline at Month 18	-23.5 units on a scale Standard Deviation 13.56	-22.8 units on a scale Standard Deviation 14.41
Change From Baseline in PANSS Total Score change from baseline at Month 21	-24.3 units on a scale Standard Deviation 13.60	-23.7 units on a scale Standard Deviation 14.66
Change From Baseline in PANSS Total Score change from baseline at Month 24	-25.5 units on a scale Standard Deviation 14.42	-24.6 units on a scale Standard Deviation 14.16
Change From Baseline in PANSS Total Score change at Endpoint (LOCF)	-16.6 units on a scale Standard Deviation 21.42	-14.1 units on a scale Standard Deviation 21.29
Change From Baseline in PANSS Total Score Baseline score	82.5 units on a scale Standard Deviation 12.03	81.5 units on a scale Standard Deviation 11.70
Change From Baseline in PANSS Total Score change from baseline at Day 8	-4.8 units on a scale Standard Deviation 5.93	-3.7 units on a scale Standard Deviation 7.04
Change From Baseline in PANSS Total Score change from baseline at Month 1	-9.4 units on a scale Standard Deviation 10.91	-8.8 units on a scale Standard Deviation 10.15
Change From Baseline in PANSS Total Score change from baseline at Month 2	-12.2 units on a scale Standard Deviation 12.19	-12.3 units on a scale Standard Deviation 11.34
Change From Baseline in PANSS Total Score change from baseline at Month 3	-14.5 units on a scale Standard Deviation 11.72	-15.0 units on a scale Standard Deviation 11.15
Change From Baseline in PANSS Total Score change from baseline at Month 4	-16.2 units on a scale Standard Deviation 13.03	-16.8 units on a scale Standard Deviation 12.34
Change From Baseline in PANSS Total Score change from baseline at Month 6	-18.5 units on a scale Standard Deviation 13.67	-18.6 units on a scale Standard Deviation 13.09
Change From Baseline in PANSS Total Score change from baseline at Month 9	-19.5 units on a scale Standard Deviation 14.72	-20.1 units on a scale Standard Deviation 14.35
Change From Baseline in PANSS Total Score change from baseline at Month 12	-21.8 units on a scale Standard Deviation 13.32	-21.2 units on a scale Standard Deviation 14.45
Change From Baseline in PANSS Total Score change from baseline at Month 15	-21.7 units on a scale Standard Deviation 14.56	-21.9 units on a scale Standard Deviation 14.18

SECONDARY outcome

Timeframe: Baseline (day 1 of core phase), day 8, month 12, 24

Change from baseline in positive symptom, negative symptom and general psychopathology subscales of the PANSS scale. The PANSS scale is designed to assess symptoms of schizophrenia by means of the 30-items. The PANSS scale provides subscores for 3 subscales, that is, the positive symptoms subscale (7 items, range 7-49), the negative symptoms subscale (7 items, range 7-49), and the general psychopathology subscale (16 items, range 16-112). Each item of the scale is to be scored on a scale of 1 (absent) to 7 (extreme). Higher scores indicate higher severity of schizophrenia symptoms.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Change From Baseline in PANSS Subscale Score Positive Subscale; Baseline score	18.4 units on a scale Standard Deviation 3.97	18.3 units on a scale Standard Deviation 4.01
Change From Baseline in PANSS Subscale Score Positive Subscale; change at Day 8	-1.5 units on a scale Standard Deviation 2.11	-1.3 units on a scale Standard Deviation 2.36
Change From Baseline in PANSS Subscale Score Positive Subscale; change at Month 12	-6.3 units on a scale Standard Deviation 4.10	-6.2 units on a scale Standard Deviation 4.35
Change From Baseline in PANSS Subscale Score Positive Subscale; change at Month 24	-6.8 units on a scale Standard Deviation 4.39	-6.7 units on a scale Standard Deviation 4.48
Change From Baseline in PANSS Subscale Score Positive Subscale; change at Endpoint (LOCF)	-4.4 units on a scale Standard Deviation 6.61	-3.8 units on a scale Standard Deviation 6.72
Change From Baseline in PANSS Subscale Score Negative Subscale; Baseline score	22.6 units on a scale Standard Deviation 4.55	22.3 units on a scale Standard Deviation 4.58
Change From Baseline in PANSS Subscale Score Negative Subscale; change at Day 8	-1.0 units on a scale Standard Deviation 1.90	-0.8 units on a scale Standard Deviation 2.10
Change From Baseline in PANSS Subscale Score Negative Subscale; change at Month 12	-4.8 units on a scale Standard Deviation 4.69	-4.7 units on a scale Standard Deviation 4.80
Change From Baseline in PANSS Subscale Score Negative Subscale; change at Month 24	-6.2 units on a scale Standard Deviation 5.19	-5.9 units on a scale Standard Deviation 4.74
Change From Baseline in PANSS Subscale Score Negative Subscale; change at Endpoint (LOCF)	-4.1 units on a scale Standard Deviation 6.13	-3.7 units on a scale Standard Deviation 5.79
Change From Baseline in PANSS Subscale Score General Psychopathology; Baseline score	41.4 units on a scale Standard Deviation 6.73	40.8 units on a scale Standard Deviation 6.59
Change From Baseline in PANSS Subscale Score General Psychopathology; change at Day 8	-2.3 units on a scale Standard Deviation 3.58	-1.6 units on a scale Standard Deviation 4.01
Change From Baseline in PANSS Subscale Score General Psychopathology; change at Month 12	-10.7 units on a scale Standard Deviation 7.19	-10.3 units on a scale Standard Deviation 7.64
Change From Baseline in PANSS Subscale Score General Psychopathology; change at Month 24	-12.5 units on a scale Standard Deviation 7.63	-12.0 units on a scale Standard Deviation 7.82
Change From Baseline in PANSS Subscale Score General Psychopathology; change at Endpoint (LOCF)	-8.1 units on a scale Standard Deviation 10.96	-6.7 units on a scale Standard Deviation 11.12

SECONDARY outcome

Timeframe: Baseline (day 1 of core phase), day 8, month 12 and 24

Change from baseline in schizophrenia symptoms were assessed through the following PANSS factor scores as described by Marder: (1) positive symptoms (range 8-56): sum of delusions, hallucinatory behavior, grandiosity, suspiciousness, stereotyped thinking, somatic concern, unusual thought content, lack of judgment and insight; (2) negative symptoms (range 7-49): sum of blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance; (3) disorganized thoughts (range 7-49): sum of conceptual disorganization, difficulty in abstract thinking, mannerisms and posturing, disorientation, poor attention, disturbance of volition, and preoccupation; (4) uncontrolled hostility/excitement (range 4-28): sum of excitement, hostility, uncooperativeness and poor impulse control; (5) anxiety/depression (range 4-28): sum of anxiety, guilt feelings, tension, and depression. Higher scores indicate higher severity of symptoms

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Change From Baseline in PANSS Marder Factor Scores Positive Symptoms Factor Score; Baseline score	22.9 units on a scale Standard Deviation 4.26	22.5 units on a scale Standard Deviation 4.39
Change From Baseline in PANSS Marder Factor Scores Positive Symptoms Factor Score; change at Day 8	-1.5 units on a scale Standard Deviation 2.22	-1.3 units on a scale Standard Deviation 2.50
Change From Baseline in PANSS Marder Factor Scores Positive Symptoms Factor Score; change at Month 12	-6.9 units on a scale Standard Deviation 4.31	-6.9 units on a scale Standard Deviation 4.76
Change From Baseline in PANSS Marder Factor Scores Positive Symptoms Factor Score; change at Month 24	-7.6 units on a scale Standard Deviation 4.48	-7.8 units on a scale Standard Deviation 4.95
Change From Baseline in PANSS Marder Factor Scores Positive Symptoms Factor Score; change at Endpoint	-5.0 units on a scale Standard Deviation 6.73	-4.7 units on a scale Standard Deviation 6.80
Change From Baseline in PANSS Marder Factor Scores Negative Symptoms Factor Score; Baseline score	22.0 units on a scale Standard Deviation 4.65	21.5 units on a scale Standard Deviation 4.95
Change From Baseline in PANSS Marder Factor Scores Negative Symptoms Factor Score; change at Day 8	-1.0 units on a scale Standard Deviation 1.93	-0.8 units on a scale Standard Deviation 2.25
Change From Baseline in PANSS Marder Factor Scores Negative Symptoms Factor Score; change at Month 12	-5.1 units on a scale Standard Deviation 4.73	-4.9 units on a scale Standard Deviation 4.88
Change From Baseline in PANSS Marder Factor Scores Negative Symptoms Factor Score; change at Month 24	-6.5 units on a scale Standard Deviation 5.16	-6.1 units on a scale Standard Deviation 5.05
Change From Baseline in PANSS Marder Factor Scores Negative Symptoms Factor Score; change at Endpoint	-4.3 units on a scale Standard Deviation 6.26	-3.8 units on a scale Standard Deviation 6.08
Change From Baseline in PANSS Marder Factor Scores Disorganized Thoughts Factor; Baseline score	19.5 units on a scale Standard Deviation 3.54	19.4 units on a scale Standard Deviation 3.41
Change From Baseline in PANSS Marder Factor Scores Disorganized Thoughts Factor; change at Day 8	-1.0 units on a scale Standard Deviation 1.61	-0.6 units on a scale Standard Deviation 2.06
Change From Baseline in PANSS Marder Factor Scores Disorganized Thoughts Factor; change at Month 12	-4.6 units on a scale Standard Deviation 3.42	-4.6 units on a scale Standard Deviation 3.78
Change From Baseline in PANSS Marder Factor Scores Disorganized Thoughts Factor; change at Month 24	-5.4 units on a scale Standard Deviation 3.90	-5.4 units on a scale Standard Deviation 3.82
Change From Baseline in PANSS Marder Factor Scores Disorganized Thoughts Factor; change at Endpoint	-3.7 units on a scale Standard Deviation 5.03	-3.2 units on a scale Standard Deviation 5.16
Change From Baseline in PANSS Marder Factor Scores Uncontrolled Hostility/Excitement; Baseline score	8.4 units on a scale Standard Deviation 2.71	8.3 units on a scale Standard Deviation 2.64
Change From Baseline in PANSS Marder Factor Scores Uncontrolled Hostility/Excitement; change at Day 8	-0.7 units on a scale Standard Deviation 1.60	-0.4 units on a scale Standard Deviation 1.47
Change From Baseline in PANSS Marder Factor Scores Uncontrolled Hostility/Excitement; change Month 12	-2.3 units on a scale Standard Deviation 2.57	-2.1 units on a scale Standard Deviation 2.62
Change From Baseline in PANSS Marder Factor Scores Uncontrolled Hostility/Excitement; change Month 24	-2.7 units on a scale Standard Deviation 2.77	-2.3 units on a scale Standard Deviation 2.73
Change From Baseline in PANSS Marder Factor Scores Uncontrolled Hostility/Excitement; change Endpoint	-1.5 units on a scale Standard Deviation 3.82	-0.8 units on a scale Standard Deviation 3.87
Change From Baseline in PANSS Marder Factor Scores Anxiety/Depression Factor; Baseline score	9.7 units on a scale Standard Deviation 2.74	9.8 units on a scale Standard Deviation 2.85
Change From Baseline in PANSS Marder Factor Scores Anxiety/Depression Factor; change at Day 8	-0.8 units on a scale Standard Deviation 1.57	-0.6 units on a scale Standard Deviation 1.72
Change From Baseline in PANSS Marder Factor Scores Anxiety/Depression Factor; change at Month 12	-2.8 units on a scale Standard Deviation 2.67	-2.7 units on a scale Standard Deviation 2.56
Change From Baseline in PANSS Marder Factor Scores Anxiety/Depression Factor; change at Month 24	-3.3 units on a scale Standard Deviation 2.90	-3.0 units on a scale Standard Deviation 2.78
Change From Baseline in PANSS Marder Factor Scores Anxiety/Depression Factor; change at Endpoint	-2.1 units on a scale Standard Deviation 3.51	-1.8 units on a scale Standard Deviation 3.47

SECONDARY outcome

Timeframe: Baseline (day 1 of core phase), day 8, month 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, 24

The Clinical Global Impression Severity (CGI-S) rating scale is a 7 point global clinical assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher scores indicate higher impression of illness severity.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score Baseline score	3.9 units on a scale Standard Deviation 0.37	3.8 units on a scale Standard Deviation 0.40
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Day 8	-0.1 units on a scale Standard Deviation 0.38	-0.1 units on a scale Standard Deviation 0.43
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 1	-0.3 units on a scale Standard Deviation 0.61	-0.3 units on a scale Standard Deviation 0.61
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 2	-0.4 units on a scale Standard Deviation 0.70	-0.5 units on a scale Standard Deviation 0.71
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 3	-0.6 units on a scale Standard Deviation 0.69	-0.6 units on a scale Standard Deviation 0.69
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 4	-0.7 units on a scale Standard Deviation 0.75	-0.8 units on a scale Standard Deviation 0.71
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 6	-0.8 units on a scale Standard Deviation 0.78	-0.8 units on a scale Standard Deviation 0.73
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 9	-0.9 units on a scale Standard Deviation 0.80	-0.9 units on a scale Standard Deviation 0.78
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 12	-1.0 units on a scale Standard Deviation 0.78	-1.0 units on a scale Standard Deviation 0.80
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 15	-0.9 units on a scale Standard Deviation 0.82	-1.0 units on a scale Standard Deviation 0.80
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 18	-1.0 units on a scale Standard Deviation 0.80	-1.0 units on a scale Standard Deviation 0.78
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 21	-1.0 units on a scale Standard Deviation 0.78	-1.1 units on a scale Standard Deviation 0.82
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Month 24	-1.1 units on a scale Standard Deviation 0.79	-1.1 units on a scale Standard Deviation 0.80
Change From Baseline in Clinical Global Impression Severity (CGI-S) Score change from baseline at Endpoint (LOCF)	-0.7 units on a scale Standard Deviation 1.14	-0.6 units on a scale Standard Deviation 1.12

SECONDARY outcome

Timeframe: Month 24 and endpoint

The Clinical Global Impression-Change (CGI-C) rating scale is used to rate the change in severity of the patient's illness compared to baseline (day 1 of core phase) on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Clinical Global Impression-Change (CGI-C) Month 24; Very Much Improved	22.9 percentage of participants 22.9	21.7 percentage of participants 21.7
Clinical Global Impression-Change (CGI-C) Month 24; Much Improved	52.9 percentage of participants 52.9	47.8 percentage of participants 47.8
Clinical Global Impression-Change (CGI-C) Month 24; Minimally Improved	17.0 percentage of participants 17.0	20.8 percentage of participants 20.8
Clinical Global Impression-Change (CGI-C) Month 24; No change	6.7 percentage of participants 6.7	7.7 percentage of participants 7.7
Clinical Global Impression-Change (CGI-C) Month 24; Minimally Worse	0.0 percentage of participants 0.0	1.0 percentage of participants 1.0
Clinical Global Impression-Change (CGI-C) Month 24; Much Worse	0.4 percentage of participants 0.4	1.0 percentage of participants 1.0
Clinical Global Impression-Change (CGI-C) Month 24; Very Much Worse	0.0 percentage of participants 0.0	0.0 percentage of participants 0.0
Clinical Global Impression-Change (CGI-C) Endpoint; Very Much Improved	17.1 percentage of participants 17.1	14.2 percentage of participants 14.2
Clinical Global Impression-Change (CGI-C) Endpoint; Much Improved	40.6 percentage of participants 40.6	35.8 percentage of participants 35.8
Clinical Global Impression-Change (CGI-C) Endpoint; Minimally Improved	17.4 percentage of participants 17.4	21.9 percentage of participants 21.9
Clinical Global Impression-Change (CGI-C) Endpoint; No change	10.6 percentage of participants 10.6	10.8 percentage of participants 10.8
Clinical Global Impression-Change (CGI-C) Endpoint; Minimally Worse	5.1 percentage of participants 5.1	6.1 percentage of participants 6.1
Clinical Global Impression-Change (CGI-C) Endpoint; Much Worse	9.1 percentage of participants 9.1	10.6 percentage of participants 10.6
Clinical Global Impression-Change (CGI-C) Endpoint; Very Much Worse	0.0 percentage of participants 0.0	0.6 percentage of participants 0.6

SECONDARY outcome

Timeframe: baseline (day 1 of core phase), month 1, 3, 6, 9, 12, 15, 18, 21 and 24

The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. Score ranges from 1 to 100, divided into 10 equal intervals to rate degree of difficulty (1, absent to 6, very severe) in each of the 4 domains. Based on 4 domains there will be 1 total score. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Changes From Baseline in Personal and Social Performance (PSP) Total Score Baseline score	55.3 units on a scale Standard Deviation 11.31	55.3 units on a scale Standard Deviation 11.07
Changes From Baseline in Personal and Social Performance (PSP) Total Score change from baseline at Month 1	4.9 units on a scale Standard Deviation 7.78	4.3 units on a scale Standard Deviation 7.65
Changes From Baseline in Personal and Social Performance (PSP) Total Score change from baseline at Month 3	7.6 units on a scale Standard Deviation 8.91	7.7 units on a scale Standard Deviation 9.02
Changes From Baseline in Personal and Social Performance (PSP) Total Score change from baseline at Month 6	9.9 units on a scale Standard Deviation 10.08	10.8 units on a scale Standard Deviation 10.32
Changes From Baseline in Personal and Social Performance (PSP) Total Score change from baseline at Month 9	11.4 units on a scale Standard Deviation 11.28	11.9 units on a scale Standard Deviation 11.03
Changes From Baseline in Personal and Social Performance (PSP) Total Score change from baseline at Month 12	12.7 units on a scale Standard Deviation 10.78	12.3 units on a scale Standard Deviation 11.27
Changes From Baseline in Personal and Social Performance (PSP) Total Score change from baseline at Month 15	12.9 units on a scale Standard Deviation 11.05	12.9 units on a scale Standard Deviation 10.82
Changes From Baseline in Personal and Social Performance (PSP) Total Score change from baseline at Month 18	14.0 units on a scale Standard Deviation 11.44	13.3 units on a scale Standard Deviation 11.44
Changes From Baseline in Personal and Social Performance (PSP) Total Score change from baseline at Month 21	14.7 units on a scale Standard Deviation 12.3	14.0 units on a scale Standard Deviation 11.69
Changes From Baseline in Personal and Social Performance (PSP) Total Score change from baseline at Month 24	15.2 units on a scale Standard Deviation 12.72	14.6 units on a scale Standard Deviation 11.72
Changes From Baseline in Personal and Social Performance (PSP) Total Score change from baseline at Endpoint (LOCF)	9.8 units on a scale Standard Deviation 15.41	8.7 units on a scale Standard Deviation 14.89

SECONDARY outcome

Timeframe: baseline (day 1 of core phase), month 6, 12 and 24

The Short Form-36 Health Survey (SF-36) is a measure of Participant-reported health status. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Two summary scale scores are computed based on weighted combinations of the 8 subscale scores: the Physical Component Summary and the Mental Component Summary. Each summary scale score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Change From Baseline in Short Form-36 Health Survey (SF-36) Physical Component, Baseline score	50.3 units on a scale Standard Deviation 8.04	50.6 units on a scale Standard Deviation 7.83
Change From Baseline in Short Form-36 Health Survey (SF-36) Physical Component, change at Month 6	1.2 units on a scale Standard Deviation 6.92	1.3 units on a scale Standard Deviation 6.52
Change From Baseline in Short Form-36 Health Survey (SF-36) Physical Component, change at Month 12	1.6 units on a scale Standard Deviation 7.62	1.2 units on a scale Standard Deviation 7.08
Change From Baseline in Short Form-36 Health Survey (SF-36) Physical Component, change at Month 24	2.2 units on a scale Standard Deviation 8.40	2.1 units on a scale Standard Deviation 6.74
Change From Baseline in Short Form-36 Health Survey (SF-36) Physical Component, change at Endpoint (LOCF)	1.7 units on a scale Standard Deviation 8.52	1.4 units on a scale Standard Deviation 7.40
Change From Baseline in Short Form-36 Health Survey (SF-36) Mental Component, Baseline score	32.1 units on a scale Standard Deviation 12.62	31.4 units on a scale Standard Deviation 12.92
Change From Baseline in Short Form-36 Health Survey (SF-36) Mental Component, change at Month 6	8.2 units on a scale Standard Deviation 11.58	9.1 units on a scale Standard Deviation 12.43
Change From Baseline in Short Form-36 Health Survey (SF-36) Mental Component, change at Month 12	10.5 units on a scale Standard Deviation 11.75	11.6 units on a scale Standard Deviation 12.77
Change From Baseline in Short Form-36 Health Survey (SF-36) Mental Component, change at Month 24	12.0 units on a scale Standard Deviation 13.34	12.3 units on a scale Standard Deviation 12.83
Change From Baseline in Short Form-36 Health Survey (SF-36) Mental Component, change at Endpoint (LOCF)	9.0 units on a scale Standard Deviation 14.99	8.7 units on a scale Standard Deviation 14.37

SECONDARY outcome

Timeframe: baseline (day 1 of core phase), month 6, 12 and 24

The EQ-5D VAS records the respondent's self-rated health on a vertical, visual analog scale, with 0 representing the worst imaginable health state and 100 representing the best imaginable health state. The EQ VAS is used as a quantitative measure of health outcome as judged by the individual respondent.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) VAS Score Baseline score	57.5 units on a scale Standard Deviation 20.94	57.6 units on a scale Standard Deviation 20.41
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) VAS Score change from baseline at Month 6	10.6 units on a scale Standard Deviation 17.31	11.9 units on a scale Standard Deviation 17.00
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) VAS Score change from baseline at Month 12	15.0 units on a scale Standard Deviation 17.38	15.6 units on a scale Standard Deviation 18.32
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) VAS Score change from baseline at Month 24	17.9 units on a scale Standard Deviation 19.48	18.6 units on a scale Standard Deviation 17.36
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) VAS Score change from baseline at Endpoint (LOCF)	13.0 units on a scale Standard Deviation 22.87	11.9 units on a scale Standard Deviation 21.54

SECONDARY outcome

Timeframe: baseline (day 1 of core phase), month 6, 12 and 24

The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. A higher score indicates an improvement in health in the Health Status Index.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Index Score change from baseline at Month 12	0.08 units on a scale Standard Deviation 0.185	0.11 units on a scale Standard Deviation 0.179
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Index Score Baseline score	0.80 units on a scale Standard Deviation 0.173	0.78 units on a scale Standard Deviation 0.181
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Index Score change from baseline at Month 6	0.06 units on a scale Standard Deviation 0.181	0.09 units on a scale Standard Deviation 0.157
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Index Score change from baseline at Month 24	0.10 units on a scale Standard Deviation 0.201	0.12 units on a scale Standard Deviation 0.161
Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Index Score change from baseline at Endpoint (LOCF)	0.06 units on a scale Standard Deviation 0.224	0.08 units on a scale Standard Deviation 0.192

SECONDARY outcome

Timeframe: baseline (day 1 of core phase), month 6, 12 and 24

The SWN-S is a patient self-rated scale developed to measure the subjective well-being for the previous 7 days of a patient under neuroleptic treatment. The SWN-S consists of 20 items (each item is rated from 1=not at all to 6=very much). The total score ranges from 20 to 120 with higher score indicating greater subjective well-being.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Change From Baseline in Subjective Well-Being Under Neuroleptics-Short Form (SWN-S) Total Score Baseline score	76.5 units on a scale Standard Deviation 17.02	76.7 units on a scale Standard Deviation 17.07
Change From Baseline in Subjective Well-Being Under Neuroleptics-Short Form (SWN-S) Total Score change from baseline at Month 6	8.4 units on a scale Standard Deviation 14.06	9.1 units on a scale Standard Deviation 14.40
Change From Baseline in Subjective Well-Being Under Neuroleptics-Short Form (SWN-S) Total Score change from baseline at Month 12	11.4 units on a scale Standard Deviation 15.81	11.1 units on a scale Standard Deviation 17.02
Change From Baseline in Subjective Well-Being Under Neuroleptics-Short Form (SWN-S) Total Score change from baseline at Month 24	13.4 units on a scale Standard Deviation 18.14	13.1 units on a scale Standard Deviation 15.76
Change From Baseline in Subjective Well-Being Under Neuroleptics-Short Form (SWN-S) Total Score change from baseline at Endpoint (LOCF)	9.7 units on a scale Standard Deviation 19.17	8.3 units on a scale Standard Deviation 17.58

SECONDARY outcome

Timeframe: baseline (day 1 of core phase), month 12 and 24

Patient's satisfaction with medication was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM). The TSQM is divided into 4 subscales (effectiveness, side effects, convenience, and global satisfaction), with the value of each subscale ranging from 0 to 100. Higher scores indicate greater treatment satisfaction.

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Change From Baseline in Patient's Treatment Satisfaction Effectiveness; Baseline score	61.9 units on a scale Standard Deviation 16.97	59.5 units on a scale Standard Deviation 16.82
Change From Baseline in Patient's Treatment Satisfaction Effectiveness; change at Month 12	6.7 units on a scale Standard Deviation 22.72	6.6 units on a scale Standard Deviation 21.99
Change From Baseline in Patient's Treatment Satisfaction Effectiveness; change at Month 24	8.5 units on a scale Standard Deviation 21.75	12.4 units on a scale Standard Deviation 20.69
Change From Baseline in Patient's Treatment Satisfaction Effectiveness; change at Endpoint (LOCF)	3.8 units on a scale Standard Deviation 23.47	4.5 units on a scale Standard Deviation 25.31
Change From Baseline in Patient's Treatment Satisfaction Side-effects; Baseline score	91.3 units on a scale Standard Deviation 19.74	87.3 units on a scale Standard Deviation 23.41
Change From Baseline in Patient's Treatment Satisfaction Side-effects; change at Month 12	2.1 units on a scale Standard Deviation 22.71	2.5 units on a scale Standard Deviation 25.66
Change From Baseline in Patient's Treatment Satisfaction Side-effects; change at Month 24	2.8 units on a scale Standard Deviation 20.93	3.5 units on a scale Standard Deviation 23.96
Change From Baseline in Patient's Treatment Satisfaction Side-effects; change at Endpoint (LOCF)	-1.4 units on a scale Standard Deviation 25.59	0.7 units on a scale Standard Deviation 28.24
Change From Baseline in Patient's Treatment Satisfaction Convenience; Baseline score	67.1 units on a scale Standard Deviation 16.66	68.4 units on a scale Standard Deviation 16.45
Change From Baseline in Patient's Treatment Satisfaction Convenience; change at Month 12	8.4 units on a scale Standard Deviation 19.10	1.0 units on a scale Standard Deviation 17.79
Change From Baseline in Patient's Treatment Satisfaction Convenience; change at Month 24	10.4 units on a scale Standard Deviation 20.49	4.7 units on a scale Standard Deviation 17.69
Change From Baseline in Patient's Treatment Satisfaction Convenience; change at Endpoint (LOCF)	7.4 units on a scale Standard Deviation 21.24	0.3 units on a scale Standard Deviation 21.68
Change From Baseline in Patient's Treatment Satisfaction Global Satisfaction; Baseline score	64.0 units on a scale Standard Deviation 18.13	62.8 units on a scale Standard Deviation 18.31
Change From Baseline in Patient's Treatment Satisfaction Global Satisfaction; change at Month 12	8.2 units on a scale Standard Deviation 18.89	7.0 units on a scale Standard Deviation 21.18
Change From Baseline in Patient's Treatment Satisfaction Global Satisfaction; change at Month 24	8.6 units on a scale Standard Deviation 21.06	9.2 units on a scale Standard Deviation 20.39
Change From Baseline in Patient's Treatment Satisfaction Global Satisfaction; change at Endpoint (LOCF)	3.0 units on a scale Standard Deviation 25.01	1.0 units on a scale Standard Deviation 26.76

SECONDARY outcome

Timeframe: baseline (day 1 of core phase), month 12 and 24

Physician's treatment satisfaction was assessed using the physician's treatment satisfaction scale which is designed to rate 4 aspects of treatment (efficacy, safety, mode of administration, and overall satisfaction), each on a scale ranging from 1 (extremely satisfied) to 7 (extremely dissatisfied).

Outcome measures

Outcome measures
Measure	Paliperidone Palmitate n=352 Participants paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=363 Participants oral antipsychotics daily treatment according to local label for maximally 24 months
Change From Baseline in Physician's Treatment Satisfaction Efficacy; Baseline score	2.7 units on a scale Standard Deviation 0.79	2.8 units on a scale Standard Deviation 0.79
Change From Baseline in Physician's Treatment Satisfaction Efficacy; change at Month 12	-0.5 units on a scale Standard Deviation 1.03	-0.4 units on a scale Standard Deviation 0.92
Change From Baseline in Physician's Treatment Satisfaction Efficacy; change at Month 24	-0.6 units on a scale Standard Deviation 1.10	-0.6 units on a scale Standard Deviation 0.98
Change From Baseline in Physician's Treatment Satisfaction Efficacy; change at Endpoint (LOCF)	-0.2 units on a scale Standard Deviation 1.46	0.0 units on a scale Standard Deviation 1.43
Change From Baseline in Physician's Treatment Satisfaction Safety; Baseline score	2.4 units on a scale Standard Deviation 0.80	2.6 units on a scale Standard Deviation 0.77
Change From Baseline in Physician's Treatment Satisfaction Safety; change at Month 12	-0.4 units on a scale Standard Deviation 0.97	-0.2 units on a scale Standard Deviation 0.90
Change From Baseline in Physician's Treatment Satisfaction Safety; change at Month 24	-0.4 units on a scale Standard Deviation 0.97	-0.3 units on a scale Standard Deviation 1.04
Change From Baseline in Physician's Treatment Satisfaction Safety; change at Endpoint (LOCF)	-0.2 units on a scale Standard Deviation 1.19	-0.0 units on a scale Standard Deviation 1.18
Change From Baseline in Physician's Treatment Satisfaction Mode of Administration: Baseline score	2.6 units on a scale Standard Deviation 0.86	2.6 units on a scale Standard Deviation 0.83
Change From Baseline in Physician's Treatment Satisfaction Mode of Administration: change at Month 12	-0.7 units on a scale Standard Deviation 1.02	-0.0 units on a scale Standard Deviation 0.92
Change From Baseline in Physician's Treatment Satisfaction Mode of Administration: change at Month 24	-0.7 units on a scale Standard Deviation 1.09	-0.1 units on a scale Standard Deviation 0.92
Change From Baseline in Physician's Treatment Satisfaction Mode of Administration: change at Endpoint (LOCF)	-0.5 units on a scale Standard Deviation 1.16	0.0 units on a scale Standard Deviation 1.04
Change From Baseline in Physician's Treatment Satisfaction Overall Satisfaction; Baseline score	2.6 units on a scale Standard Deviation 0.78	2.7 units on a scale Standard Deviation 0.74
Change From Baseline in Physician's Treatment Satisfaction Overall Satisfaction; change at Month 12	-0.5 units on a scale Standard Deviation 0.95	-0.3 units on a scale Standard Deviation 0.84
Change From Baseline in Physician's Treatment Satisfaction Overall Satisfaction; change at Month 24	-0.6 units on a scale Standard Deviation 1.00	-0.3 units on a scale Standard Deviation 0.86
Change From Baseline in Physician's Treatment Satisfaction Overall Satisfaction; change at Endpoint (LOCF)	-0.2 units on a scale Standard Deviation 1.25	0.1 units on a scale Standard Deviation 1.16

Adverse Events

Paliperidone Palmitate

Serious events: 42 serious events

Other events: 208 other events

Deaths: 0 deaths

Oral Antipsychotics

Serious events: 48 serious events

Other events: 208 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

EMEA Medical Affairs Director Psychiatry

Janssen-Cilag Germany

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the Sponsor for review at least 60 days prior to submission for publication or presentation. No paper that incorporates Confidential Information will be submitted for publication without Sponsor's prior written consent. If requested in writing, such publication will be withheld for up to an additional 60 calendar days. A publication from the individual Study site data will not be published until the combined results have been published.
Publication restrictions are in place

Restriction type: OTHER

Measure	Paliperidone Palmitate n=376 participants at risk 2 weeks oral paliperidone treatment followed by intramuscular injection with 150 mg paliperidone palmitate equivalent on Day 1 of the core treatment phase, 100 mg equivalent on Day 8, 75 mg equivalent on Day 38 and flexible dosing with 25, 50, 75, 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=388 participants at risk Oral antipsychotics daily treatment according to local label for maximally 24 months
Cardiac disorders Cardiac arrest	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Gastrointestinal disorders Abdominal pain	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Gastrointestinal disorders Haemorrhoids	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.26% 1/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Gastrointestinal disorders Salivary hypersecretion	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.26% 1/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
General disorders Sudden death	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.26% 1/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Hepatobiliary disorders Cholecystitis chronic	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Infections and infestations Bronchitis	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Infections and infestations Hepatic echinococciasis	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.26% 1/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Infections and infestations Pneumonia	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.26% 1/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Infections and infestations Sinusitis	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Injury, poisoning and procedural complications Foreign body	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Injury, poisoning and procedural complications Multiple injuries	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Injury, poisoning and procedural complications Overdose	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.26% 1/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.26% 1/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Investigations Alanine aminotransferase increased	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Musculoskeletal and connective tissue disorders Prognathism	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.26% 1/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Nervous system disorders Epilepsy	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.26% 1/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Acute psychosis	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Agitation	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.52% 2/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Alcohol abuse	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.52% 2/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Anxiety	0.53% 2/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Psychotic disorder	1.9% 7/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	2.1% 8/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Schizophrenia	5.6% 21/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	5.7% 22/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Schizophrenia, paranoid type	0.80% 3/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	1.0% 4/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Suicide attempt	0.00% 0/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.52% 2/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Renal and urinary disorders Calculus bladder	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Reproductive system and breast disorders Varicocele	0.27% 1/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events

Measure	Paliperidone Palmitate n=376 participants at risk 2 weeks oral paliperidone treatment followed by intramuscular injection with 150 mg paliperidone palmitate equivalent on Day 1 of the core treatment phase, 100 mg equivalent on Day 8, 75 mg equivalent on Day 38 and flexible dosing with 25, 50, 75, 100 or 150 mg equivalent once monthly thereafter	Oral Antipsychotics n=388 participants at risk Oral antipsychotics daily treatment according to local label for maximally 24 months
General disorders Fatigue	2.4% 9/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	1.8% 7/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
General disorders Injection site pain	6.4% 24/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	0.00% 0/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Infections and infestations Influenza	1.6% 6/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	2.1% 8/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Infections and infestations Nasopharyngitis	6.6% 25/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	5.2% 20/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Investigations Weight decreased	2.4% 9/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	2.3% 9/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Ear and labyrinth disorders Vertigo	2.1% 8/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	1.5% 6/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Gastrointestinal disorders Diarrhoea	2.1% 8/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	1.8% 7/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Gastrointestinal disorders Nausea	3.2% 12/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	3.4% 13/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
General disorders Asthenia	1.9% 7/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	2.1% 8/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Investigations Weight increased	15.4% 58/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	16.8% 65/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Metabolism and nutrition disorders Increased appetite	2.4% 9/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	3.1% 12/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Musculoskeletal and connective tissue disorders Muscle rigidity	3.2% 12/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	2.1% 8/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Nervous system disorders Akathisia	5.6% 21/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	5.7% 22/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Nervous system disorders Headache	10.6% 40/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	8.8% 34/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Nervous system disorders Sedation	1.6% 6/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	2.6% 10/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Nervous system disorders Somnolence	3.5% 13/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	5.7% 22/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Nervous system disorders Tremor	5.9% 22/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	4.4% 17/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Agitation	2.4% 9/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	2.3% 9/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Anxiety	5.9% 22/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	5.9% 23/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Depression	2.9% 11/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	2.3% 9/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Insomnia	11.2% 42/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	10.1% 39/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Schizophrenia	2.4% 9/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	3.9% 15/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Psychiatric disorders Suicidal ideation	5.3% 20/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	5.9% 23/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
Reproductive system and breast disorders Amenorrhoea	2.9% 11/376 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events	1.8% 7/388 • from randomization until maximally month 24 Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events