Trial Outcomes & Findings for A 6 Month Study to Compare the Metabolic Effects of Paliperidone ER and Olanzapine in Patients With Schizophrenia (NCT NCT00645099)

NCT ID: NCT00645099

Last Updated: 2014-05-08

Results Overview

Plasma fasting TG and HDL concentrations were measured to determine the TG:HDL ratio.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

462 participants

Primary outcome timeframe

Baseline to End Point (up to 6 months)

Results posted on

2014-05-08

Participant Flow

Three subjects of the 462 enrolled did not receive study medication and were excluded from analysis: 2 subjects were randomized by mistake by the investigator and 1 subject withdrew consent before first intake of study medication. The ITT population consisted of 459 subjects who took at least one dose of study medication.

Participant milestones

Participant milestones
Measure	Paliperidone Extended Release (ER) 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Study STARTED	239	220
Overall Study COMPLETED	168	178
Overall Study NOT COMPLETED	71	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Paliperidone Extended Release (ER) 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Overall Study Lack of Efficacy	15	6
Overall Study Withdrawal by Subject	30	22
Overall Study Lost to Follow-up	6	4
Overall Study Adverse Event	11	5
Overall Study Other	9	5

Baseline Characteristics

A 6 Month Study to Compare the Metabolic Effects of Paliperidone ER and Olanzapine in Patients With Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Paliperidone ER n=239 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=220 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months	Total n=459 Participants Total of all reporting groups
Age, Continuous	38.8 years STANDARD_DEVIATION 11.1 • n=5 Participants	37.5 years STANDARD_DEVIATION 11.4 • n=7 Participants	38.2 years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	106 Participants n=5 Participants	87 Participants n=7 Participants	193 Participants n=5 Participants
Sex: Female, Male Male	133 Participants n=5 Participants	133 Participants n=7 Participants	266 Participants n=5 Participants
Body Mass Index (BMI)	26.9 kg/m² STANDARD_DEVIATION 6.31 • n=5 Participants	27.0 kg/m² STANDARD_DEVIATION 5.73 • n=7 Participants	26.9 kg/m² STANDARD_DEVIATION 6.03 • n=5 Participants
Waist	92.2 cm STANDARD_DEVIATION 14.4 • n=5 Participants	93.3 cm STANDARD_DEVIATION 15.6 • n=7 Participants	92.7 cm STANDARD_DEVIATION 14.9 • n=5 Participants
Weight	75.9 kg STANDARD_DEVIATION 17.0 • n=5 Participants	77.9 kg STANDARD_DEVIATION 16.5 • n=7 Participants	76.9 kg STANDARD_DEVIATION 16.8 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Population: The primary end point analysis set consisted of 413 patients, i.e., all patients who received study medication at least once and had baseline and post-baseline TG and HDL data. Data of patients with missing TG or HDL values or who started or changed lipid-lowering medication during the trial were excluded from analysis.

Plasma fasting TG and HDL concentrations were measured to determine the TG:HDL ratio.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=215 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=198 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline to End Point in the Triglycerides (TG) to High Density Lipoprotein (HDL) Ratio (TG:HDL Ratio)	-0.08 Ratio Standard Deviation 1.10	0.42 Ratio Standard Deviation 1.19

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.

The TG level was assessed under fasted conditions.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=223 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=203 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline to End Point in Triglycerides	-0.01 mmol/L Standard Deviation 0.77	0.36 mmol/L Standard Deviation 0.96

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

The HDL level was assessed under fasted conditions.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=216 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=198 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline to End Point in High Density Lipoprotein	0.01 mmol/L Standard Deviation 0.25	-0.04 mmol/L Standard Deviation 0.24

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Population: Safety data were analyzed using the Intent-to-Treat (ITT) analysis set for safety and consisted of 459 patients, i.e., all patients who received study medication at least once and provided any post-baseline safety data. Changes from baseline could only be calculated for patients with paired data.

The total cholesterol level was assessed under fasted conditions.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=223 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=203 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline to End Point in Total Cholesterol	0.0263 mmol/L Standard Deviation 0.7841	0.2886 mmol/L Standard Deviation 0.8493

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Population: Safety data were analyzed using the ITT analysis set for safety and consisted of 459 patients, i.e., all patients who received study medication at least once and provided any post-baseline safety data. Changes from baseline could only be calculated for patients with paired data.

The level of low density lipoprotein cholesterol was calculated using the Friedwald QT formula.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=216 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=194 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline to End Point in Low Density Lipoprotein Cholesterol (Friedwald QT)	-0.0029 mmol/L Standard Deviation 0.6726	0.1892 mmol/L Standard Deviation 0.7361

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

The insulin level was assessed under fasted conditions.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=209 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=182 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline to End Point in Converted Insulin	2.7397 pmol/L Standard Deviation 89.9776	17.2327 pmol/L Standard Deviation 84.6255

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Outcome measures

Outcome measures
Measure	Paliperidone ER n=14 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=13 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline to End Point in Fasting Glucose	-0.2071 mmol/L Standard Deviation 0.4953	0.0769 mmol/L Standard Deviation 0.4781

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post baseline data for the particular secondary efficacy parameter under discussion.

HOMA-%B is used to assess beta-cell function. HOMA-%B is a dimensionless measure of beta-cell function (higher values present increased insulin secretion for a given glucose level). HOMA-%B is normalized so that lean, healthy individuals will have values of HOMA-%B close to 100%.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=183 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=174 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline to End Point in Homeostatic Model Assessment of Beta-cell Function (HOMA-%B)	-7.54 dimensionless Standard Deviation 85.91	18.82 dimensionless Standard Deviation 147.63

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

HOMA-IR is used to assess insulin resistance (IR). HOMA-IR is a dimensionless measure of insulin resistance (higher values present more insulin resistance. HOMA-IR are normalized so that lean, healthy individuals will have values of HOMA-IR close to 1.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=184 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=174 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline to End Point in Homeastatic Model Assessment of Insulin Resistance (HOMA-IR)	0.28 dimensionless Standard Deviation 5.39	0.43 dimensionless Standard Deviation 5.37

SECONDARY outcome

Timeframe: 6 months

Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement.Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.

Fasting plasma glucose ≥126 mg/dL or 2-hour post-load plasma glucose ≥200 mg/dL during an oral glucose tolerance test (OGTT) or initiated use of glucose-lowering agents during the course of the study.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=239 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=220 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Number of Patients Meeting the Criteria for Type 2 Diabetes Mellitus During Follow-up	21 Participants	23 Participants

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Population: The secondary end point analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement.Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.

Glucose ≥140 mg/dL, \<200 mg/dL after a 75g OGTT.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=217 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=198 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Number of Patients With Onset of Impaired Glucose Tolerance	36 Participants	33 Participants

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Post-baseline glucose level under fasted conditions ≥100 mg/dL but \<126 mg/dL.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=223 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=203 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Number of Patients With Impaired Fasting Glucose	68 Participants	66 Participants

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

The insulinogenic index, defined as (insulin at 30 min - insulin at 0)/(glucose at 30 min \[G(30)\] - glucose at 0 \[G(0)\]) was used as a measure of early insulin secretion in response to the OGTT. Because the index is undefined when G(30)-G(0)=0, and poorly defined when G(30)-G(0)\<0, the index was only calculated when G(30)\>G(0).

Outcome measures

Outcome measures
Measure	Paliperidone ER n=154 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=147 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline at End Point of the Insulinogenic Index	2.21 pM/mM Standard Deviation 173.46	33.78 pM/mM Standard Deviation 259.56

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

As another measure of beta-cell function, the relationship between plasma insulin and glucose concentrations during the OGTT was calculated using a simplified version of the method described by Mari et al. (Mari A, Sallas WM, He YL, Watson C, Ligueros-Saylan M, Dunning BE, Deacon CF, Holst JJ, Foley JE. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab. 2005; 90:4888-4894.).

Outcome measures

Outcome measures
Measure	Paliperidone ER n=183 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=169 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline at End Point of Mari-Type Analysis of Glucose Sensitivity for Insulin	8.63 pM/mM Standard Deviation 79.53	17.28 pM/mM Standard Deviation 94.51

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Patients were weighed lightly clothed. The same amount of clothing had to be worn each time.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=235 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=214 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline at End Point in Body Weight	1.16 kg Standard Deviation 4.57	3.81 kg Standard Deviation 5.87

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

BMI is calculated by dividing the body weight (in kg) by the square of height (in meters).

Outcome measures

Outcome measures
Measure	Paliperidone ER n=235 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=214 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline at End Point in Body Mass Index (BMI)	0.43 kg/m² Standard Deviation 1.59	1.32 kg/m² Standard Deviation 1.99

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Patients had to be instructed to stand erect with abdomen relaxed, arms at sides, feet together, and weight divided equally over both legs. The tape measure was placed around the bare abdomen midway between the palpated iliac crest and the palpated lowest rib margin in the left and right mid-axillary lines. A nonstretchable tape was evenly placed around the natural waist covering the left and right natural-waist marks. The measurement scale had to face outward, and there could not be any twists in the tape. The tape had to be just touching the skin but not compressing the soft tissue.

Outcome measures

Outcome measures
Measure	Paliperidone ER n=231 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=213 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline at End Point in Waist Circumference	0.70 cm Standard Deviation 5.39	3.38 cm Standard Deviation 6.18

SECONDARY outcome

Timeframe: 6 months

Population: The secondary endpoint analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. In this case, the total number of patients in the analysis set depends on the number of patients without metabolic syndrome at baseline.

Metabolic syndrome is defined according the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP/ATPIII) of which 3 out of 5 criteria must be met: * waist circumference men \> 102 cm; waist circumference women \> 88 cm * TG ≥ 150 mg/dL * HDL cholesterol men \<40 mg/dL; HDL cholesterol women \<50 mg/dL * Blood pressure systolic ≥ 130 mmHg; Blood pressure diastolic ≥ 85 mmHg * Fasting glucose ≥ 110 mg /dL

Outcome measures

Outcome measures
Measure	Paliperidone ER n=174 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=163 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Number of Patients First Meeting the NCEP/ATP III Criteria for Metabolic Syndrome During Follow-up	23 Participants	38 Participants

SECONDARY outcome

Timeframe: Baseline to End Point (up to 6 months)

Population: The secondary endpoint analysis set included all patients who received study medication at least once and provided ≥1 post-baseline efficacy measurement. Therefore, the total number of patients in the analysis set depends on the number of patients having post-baseline data for the particular secondary efficacy parameter under discussion.

PANSS is an investigator-rated 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The PANSS provided a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each rated on a scale of 1 (absent) to 7 (extreme).

Outcome measures

Outcome measures
Measure	Paliperidone ER n=234 Participants 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=214 Participants 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Change From Baseline to End Point in Total Positive and Negative Syndrome Scale Score (PANSS)	-13.50 points on a scale Standard Deviation 15.86	-16.60 points on a scale Standard Deviation 15.02

Adverse Events

Paliperidone ER

Serious events: 21 serious events

Other events: 98 other events

Deaths: 0 deaths

Olanzapine

Serious events: 12 serious events

Other events: 93 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

EMEA Therapeutic Area Leader CNS

Janssen-Cilag Germany

Phone: +492137955153

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Paliperidone ER n=239 participants at risk 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=220 participants at risk 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Psychiatric disorders Psychiatric symptom	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Schizophrenia	3.3% 8/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Psychotic disorder	2.5% 6/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Depression	0.84% 2/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Psychiatric decompensation	0.00% 0/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.91% 2/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Intentional self-injury	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Nervousness	0.00% 0/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Schizophrenia, paranoid type	0.00% 0/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Suicide attempt	0.00% 0/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Blood and lymphatic system disorders Leukopenia	0.84% 2/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Blood and lymphatic system disorders Agranulocytosis	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Blood and lymphatic system disorders Neutropenia	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
General disorders Asthenia	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
General disorders Fatigue	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Infections and infestations Mastitis	0.00% 0/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.00% 0/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Respiratory, thoracic and mediastinal disorders Cough	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.

Measure	Paliperidone ER n=239 participants at risk 6-mg or 9-mg tablet once daily flexible dosing for 6 months	Olanzapine n=220 participants at risk 10-15 mg (using 5-mg or 10-mg tablets) once daily flexible dosing for 6 months
Investigations Weight increased	9.6% 23/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	18.2% 40/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Investigations Blood creatine phosphokinase increased	2.9% 7/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	2.3% 5/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Investigations Alanine aminotransferase increased	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Investigations Blood glucose increased	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Investigations Gamma-glutamyltransferase increased	0.42% 1/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Investigations Waist circumference increased	0.00% 0/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.8% 4/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Investigations Weight decreased	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Investigations Blood triglycerides increased	0.00% 0/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Nervous system disorders Somnolence	3.3% 8/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	9.5% 21/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Nervous system disorders Headache	4.6% 11/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	4.1% 9/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Nervous system disorders Sedation	2.1% 5/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	2.7% 6/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Nervous system disorders Akathisia	2.5% 6/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.91% 2/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Nervous system disorders Dizziness	2.1% 5/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.91% 2/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Nervous system disorders Dyskinesia	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.91% 2/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Nervous system disorders Hypersomnia	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.91% 2/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Insomnia	9.6% 23/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Anxiety	4.2% 10/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Tension	2.1% 5/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Agitation	1.7% 4/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Schizophrenia	1.7% 4/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Psychotic disorder	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Restlessness	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Psychiatric disorders Depression	0.00% 0/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
General disorders Fatigue	2.1% 5/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.91% 2/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
General disorders Irritability	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Infections and infestations Influenza	0.84% 2/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Infections and infestations Nasopharyngitis	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Infections and infestations Urinary tract infection	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Gastrointestinal disorders Dyspepsia	1.7% 4/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.91% 2/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Gastrointestinal disorders Nausea	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.45% 1/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Reproductive system and breast disorders Amenorrhoea	3.3% 8/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Reproductive system and breast disorders Galactorrhoea	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Metabolism and nutrition disorders Increased appetite	1.7% 4/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	2.3% 5/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Vascular disorders Hypertension	0.84% 2/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	1.4% 3/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	1.3% 3/239 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.	0.00% 0/220 • From informed consent up to 6 months (+/- 7 days) of treatment. In case subjects had discontinued before completing treatment, the last data were obtained at the early discontinuation visit.