Trial Outcomes & Findings for Long-term Extension Trial of Asenapine in Subjects With Schizophrenia (Study P06125) (NCT NCT01142596)

Results Overview

For each participant, change in weight from preceding 6-week double-blind Study P06124 baseline to the final assessment of extension study P06125 was determined (calculated as final assessment value minus baseline value). Final assessment was last evaluation of participant in study, whether participant completed or did not complete study. Participants were allocated to categories of percentage change from defined baseline to final assessment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

201 participants

Primary outcome timeframe

Study P06124 baseline and P06125 study from Day 1 up to Week 52

Results posted on

2024-05-28

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo/Asenapine Participants in this group had received double-blind placebo BID in preceding study P06124 (NCT01098110), and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Overall Study STARTED	44	157
Overall Study COMPLETED	15	71
Overall Study NOT COMPLETED	29	86

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Asenapine Participants in this group had received double-blind placebo BID in preceding study P06124 (NCT01098110), and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Overall Study Withdrawal by Subject	9	35
Overall Study Adverse Event	8	35
Overall Study Lack of Efficacy	5	9
Overall Study Lost to Follow-up	2	3
Overall Study Other reason (not specified)	5	4

Baseline Characteristics

Long-term Extension Trial of Asenapine in Subjects With Schizophrenia (Study P06125)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Asenapine n=44 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=157 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Total n=201 Participants Total of all reporting groups
Age, Continuous	42.50 years STANDARD_DEVIATION 13.39 • n=93 Participants	41.82 years STANDARD_DEVIATION 11.44 • n=4 Participants	41.97 years STANDARD_DEVIATION 11.86 • n=27 Participants
Sex: Female, Male Female	26 Participants n=93 Participants	79 Participants n=4 Participants	105 Participants n=27 Participants
Sex: Female, Male Male	18 Participants n=93 Participants	78 Participants n=4 Participants	96 Participants n=27 Participants

PRIMARY outcome

Timeframe: Study P06124 baseline and P06125 study from Day 1 up to Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 final assessment

For each participant, change in weight from preceding 6-week double-blind Study P06124 baseline to the final assessment of extension study P06125 was determined (calculated as final assessment value minus baseline value). Final assessment was last evaluation of participant in study, whether participant completed or did not complete study. Participants were allocated to categories of percentage change from defined baseline to final assessment.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=31 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=138 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment Increase ≥7%	12.9 percentage of participants in category	26.8 percentage of participants in category
Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment Change within ± 7%	64.5 percentage of participants in category	61.6 percentage of participants in category
Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment Decrease ≥7%	22.6 percentage of participants in category	11.6 percentage of participants in category

PRIMARY outcome

Timeframe: Study P06125 baseline up to Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and final assessment

For each participant, change in weight from extension study P06125 baseline to the final assessment of extension study was determined (calculated as final assessment value minus baseline value). Final assessment was last evaluation of participant in study, whether participant completed or did not complete study. Participants were allocated to categories of percentage change from defined baseline to final assessment.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=31 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=138 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment Increase ≥7%	22.6 percentage of participants in category	23.9 percentage of participants in category
Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment Change within ± 7%	64.5 percentage of participants in category	62.3 percentage of participants in category
Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment Decrease ≥7%	12.9 percentage of participants in category	13.8 percentage of participants in category

PRIMARY outcome

Timeframe: Study P06124 baseline and study P06125 Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 Week 52

For each participant, change in BMI from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=15 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=70 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06124 Baseline in Body Mass Index (BMI) at Week 52	-0.04 kg/m^2 Standard Deviation 2.83	0.91 kg/m^2 Standard Deviation 2.74

PRIMARY outcome

Timeframe: Study P06125 baseline and Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and Week 52

For each participant, change in BMI from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=15 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=70 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06125 Baseline in BMI at Week 52	0.35 kg/m^2 Standard Deviation 2.48	0.75 kg/m^2 Standard Deviation 2.41

PRIMARY outcome

Timeframe: Up to 30 days after last dose of study drug (Up to approximately 56 weeks)

Population: All participants randomized in study P06125 who received at least one dose of study drug

This measure reports the overall number of participants with any of a group of adverse events that were defined to represent extrapyramidal symptoms. The number of participants with each of the individual adverse events within this definition is also presented, for terms that occurred in at least one participant. For this measure, all adverse event terms within the Medical Dictionary for Regulatory Activities (MedDRA) Standardized MedDRA Query (SMQ) for "extrapyramidal syndrome" were treated as extrapyramidal symptoms.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=44 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=157 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Number of Participants With Extrapyramidal Symptoms Any extrapyramidal symptom	11 participants	34 participants
Number of Participants With Extrapyramidal Symptoms Restlessness	1 participants	2 participants
Number of Participants With Extrapyramidal Symptoms Akathisia	2 participants	13 participants
Number of Participants With Extrapyramidal Symptoms Bradykinesia	0 participants	2 participants
Number of Participants With Extrapyramidal Symptoms Dyskinesia	2 participants	3 participants
Number of Participants With Extrapyramidal Symptoms Dystonia	0 participants	2 participants
Number of Participants With Extrapyramidal Symptoms Extrapyramidal disorder	2 participants	6 participants
Number of Participants With Extrapyramidal Symptoms Muscle rigidity	2 participants	1 participants
Number of Participants With Extrapyramidal Symptoms Parkinsonism	0 participants	1 participants
Number of Participants With Extrapyramidal Symptoms Tardive dyskinesia	0 participants	1 participants
Number of Participants With Extrapyramidal Symptoms Tremor	4 participants	6 participants
Number of Participants With Extrapyramidal Symptoms Parkinsonian gait	1 participants	0 participants
Number of Participants With Extrapyramidal Symptoms Oromandibular dystonia	1 participants	0 participants
Number of Participants With Extrapyramidal Symptoms Blepharospasm	1 participants	0 participants
Number of Participants With Extrapyramidal Symptoms Oculogyric crisis	0 participants	1 participants
Number of Participants With Extrapyramidal Symptoms Muscle tightness	0 participants	1 participants
Number of Participants With Extrapyramidal Symptoms Musculoskeletal stiffness	1 participants	2 participants
Number of Participants With Extrapyramidal Symptoms Gait disturbance	0 participants	1 participants

PRIMARY outcome

Timeframe: Study P06124 baseline and P06125 study from Day 1 up to Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 endpoint assessment

Change in DIEPSS Total Score from preceding 6-week double-blind Study P06124 baseline to endpoint assessment of extension study P06125 was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Items 1 through 8 are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Each item is rated from 0 (none, normal) to 4 (severe). The Total Score is the sum of scores on Items 1 through 8, with a range from 0 (normal) to 32 (severe). Negative values of change from baseline represent improvement in symptoms.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=44 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=153 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06124 Baseline in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score at Endpoint	-0.11 score on a scale Standard Deviation 1.99	-0.46 score on a scale Standard Deviation 2.54

PRIMARY outcome

Timeframe: Study P06125 baseline up to Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and endpoint assessment

Change in DIEPSS Total Score from extension study P06125 baseline to the endpoint assessment of extension study was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Items 1 through 8 are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Each item is rated from 0 (none, normal) to 4 (severe). The Total Score is the sum of scores on Items 1 through 8, with a range from 0 (normal) to 32 (severe). Negative values of change from baseline represent improvement in symptoms.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=44 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=154 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06125 Baseline in DIEPSS Total Score at Endpoint	0.25 score on a scale Standard Deviation 1.57	-0.03 score on a scale Standard Deviation 1.90

PRIMARY outcome

Timeframe: Study P06124 baseline and P06125 study from Day 1 up to Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 endpoint assessment

Change in DIEPSS Item 9 (Global) Score from preceding 6-week double-blind Study P06124 baseline to endpoint assessment of extension study P06125 was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Each item is rated from 0 (none, normal) to 4 (severe). Negative values of change from baseline represent improvement in symptoms.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=44 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=153 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06124 Baseline in DIEPSS Item 9 Score at Endpoint	0.14 score on a scale Standard Deviation 0.63	-0.01 score on a scale Standard Deviation 0.73

PRIMARY outcome

Timeframe: Study P06125 baseline up to Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and endpoint assessment

Change in DIEPSS Item 9 (Global) Score from extension study P06125 baseline to the endpoint assessment of extension study was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Each item is rated from 0 (none, normal) to 4 (severe). Negative values of change from baseline represent improvement in symptoms.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=44 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=154 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06125 Baseline in DIEPSS Item 9 Score at Endpoint	0.18 score on a scale Standard Deviation 0.69	-0.02 score on a scale Standard Deviation 0.62

PRIMARY outcome

Timeframe: Study P06124 baseline and study P06125 Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 Week 52

For each participant, change in HbA1c from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=15 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=68 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06124 Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52	-0.09 percentage of HbA1c Standard Deviation 0.44	-0.02 percentage of HbA1c Standard Deviation 0.82

PRIMARY outcome

Timeframe: Study P06125 baseline and Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and Week 52

For each participant, change in HbA1c from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=15 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=69 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06125 Baseline in HbA1c at Week 52	0.21 percentage of HbA1c Standard Deviation 0.36	0.12 percentage of HbA1c Standard Deviation 1.02

PRIMARY outcome

Timeframe: Study P06124 baseline and study P06125 Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 Week 52

For each participant, change in fasting glucose from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=14 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=64 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06124 Baseline in Fasting Glucose at Week 52	0.37 mmol/L Standard Deviation 1.00	0.28 mmol/L Standard Deviation 1.93

PRIMARY outcome

Timeframe: Study P06125 baseline and Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and Week 52

For each participant, change in fasting glucose from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=14 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=65 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06125 Baseline in Fasting Glucose at Week 52	0.60 mmol/L Standard Deviation 1.79	0.00 mmol/L Standard Deviation 2.16

PRIMARY outcome

Timeframe: Study P06124 baseline and study P06125 Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 Week 52

For each participant, change in insulin from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=14 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=69 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06124 Baseline in Insulin at Week 52	4.06 μIU/mL Standard Deviation 16.27	2.24 μIU/mL Standard Deviation 16.06

PRIMARY outcome

Timeframe: Study P06125 baseline and Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and Week 52

For each participant, change in insulin from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=14 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=69 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06125 Baseline in Insulin at Week 52	-5.61 μIU/mL Standard Deviation 28.89	0.56 μIU/mL Standard Deviation 17.88

PRIMARY outcome

Timeframe: Study P06124 baseline and study P06125 Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 Week 52

For each participant, change in prolactin from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=15 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=70 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06124 Baseline in Prolactin at Week 52	-37.46 μg/L Standard Deviation 68.83	-20.98 μg/L Standard Deviation 47.14

PRIMARY outcome

Timeframe: Study P06125 baseline and Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and Week 52

For each participant, change in prolactin from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=15 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=70 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Change From Study P06125 Baseline in Prolactin at Week 52	10.91 μg/L Standard Deviation 20.58	-1.59 μg/L Standard Deviation 17.22

PRIMARY outcome

Timeframe: Up to 30 days after last dose of study drug (Up to approximately 56 weeks)

Population: All participants randomized in study P06125 who received at least one dose of study drug

An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with study drug administration, whether or not considered related to study drug. A serious AE (SAE) is any AE occurring at any dose that results in death, is life-threatening, results in hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. In addition, an important medical event that may not result in death, be life-threatening, or require hospitalization may be considered an SAE when it may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=44 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=157 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Number of Participants With Serious Adverse Events (AEs)	5 participants	32 participants

PRIMARY outcome

Timeframe: Up to 30 days after last dose of study drug (Up to approximately 56 weeks)

Population: All participants randomized in study P06125 who received at least one dose of study drug

An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with study drug administration, whether or not considered related to study drug. This measure presents the number of participants with at least one AEs that was non-serious (i.e., was not determined to be an SAE).

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=44 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=157 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Number of Participants With Non-serious AEs	40 participants	131 participants

PRIMARY outcome

Timeframe: Study P06124 baseline and P06125 study baseline and Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug

The percentage of participants with abnormal ECG findings is reported for three time points: 6-week double-blind study P06124 baseline, extension study P06125 baseline and extension study Week 52.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=44 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=157 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52 P06124 baseline (N = 43, 153)	41.9 percentage of participants	24.8 percentage of participants
Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52 P06125 baseline (N = 44, 156)	34.1 percentage of participants	26.9 percentage of participants
Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52 Week 52 (N = 14, 70)	42.9 percentage of participants	25.7 percentage of participants

PRIMARY outcome

Timeframe: P06125 study from Day 1 up to Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug

This measure presents the number of participants who used antiparkinsonian drugs started on or after the start of study treatment in extension study P06125. Antiparkinsonian drugs were defined as those categorized into the N04 code (antiparkinson drugs) of the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) classification system.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=44 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=157 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Number of Participants Who Took Antiparkinsonian Drugs Any antiparkinsonian drug	12 participants	40 participants
Number of Participants Who Took Antiparkinsonian Drugs Biperiden	4 participants	8 participants
Number of Participants Who Took Antiparkinsonian Drugs Biperiden hydrochloride	3 participants	16 participants
Number of Participants Who Took Antiparkinsonian Drugs Procyclidine	2 participants	1 participants
Number of Participants Who Took Antiparkinsonian Drugs Trihexyphenidyl	0 participants	3 participants
Number of Participants Who Took Antiparkinsonian Drugs Trihexyphenidyl hydrochloride	1 participants	7 participants
Number of Participants Who Took Antiparkinsonian Drugs Benzatropine mesilate	4 participants	5 participants

PRIMARY outcome

Timeframe: P06124 study baseline and Day 42, and P06125 study from Day 1 up to Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, had PANSS measurement at P06125 baseline and at least one post-baseline PANSS measurement, and were study P06124 Responders

Median time to loss of effect from P06125 extension study baseline was estimated using Kaplan-Meier product-limit method. Result reported in Responders, participants with ≥30% decrease from study P06124 baseline in Positive and Negative Syndrome Scale (PANSS, schizophrenia symptom scale) Total Score at the end of study P06124. Investigator or subinvestigator was to determine whether the study drug failed to maintain effect based on occurrence of any of the following: 1) Increase in PANSS Total Score ≥30% from P06125 extension study baseline, 2) Determination that participant's schizophrenic symptomatology had deteriorated requiring one or more of defined interventions (add new antipsychotic drug, increase in level of psychiatric outpatient care, or hospitalization/increase in level of hospitalization for psychiatric need), 3) Clinical Global Impression-Severity (CGI-S) score ≥6, 4) Discontinuation from study because of lack of efficacy, 5) AE/SAE of worsening of schizophrenia.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=25 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=101 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Median Time to Loss of Effect in Responders	357.0 days Interval 18.0 to Data were insufficient to calculate upper 95% confidence interval limit	177.0 days Interval 91.0 to Data were insufficient to calculate upper 95% confidence interval limit

PRIMARY outcome

Timeframe: P06124 study baseline and Day 42, and P06125 study from Day 1 up to Week 52

Population: All participants randomized in study P06125 who received at least one dose of study drug, had PANSS measurement at P06125 baseline and at least one post-baseline PANSS measurement, and were study P06124 Non-Responders

Median time to loss of effect from P06125 extension study baseline was estimated using Kaplan-Meier product-limit method. Result reported in Non-Responders, participants without ≥30% decrease from study P06124 baseline in PANSS Total Score at the end of study P06124. Investigator or subinvestigator was to determine whether the study drug failed to maintain effect based on occurrence of any of the following: 1) Increase in PANSS Total Score ≥30% from P06125 extension study baseline, 2) Determination that participant's schizophrenic symptomatology had deteriorated requiring one or more of defined interventions (add new antipsychotic drug, increase in level of psychiatric outpatient care, or hospitalization/increase in level of hospitalization for psychiatric need), 3) Clinical Global Impression-Severity (CGI-S) score ≥6, 4) Discontinuation from study because of lack of efficacy, 5) AE/SAE of worsening of schizophrenia.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=19 Participants Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=52 Participants Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Median Time to Loss of Effect in Non-Responders	53.0 days Interval 14.0 to Data were insufficient to calculate upper 95% confidence interval limit	368.0 days Interval 229.0 to Data were insufficient to calculate upper 95% confidence interval limit

Adverse Events

Placebo/Asenapine

Serious events: 5 serious events

Other events: 34 other events

Deaths: 0 deaths

Asenapine 5/10 mg BID

Serious events: 32 serious events

Other events: 98 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee It is planned to first publish/present trial results together with the other sites, unless permission is obtained from Sponsor to publish separate results. Sponsor must be able to review all proposed results communications regarding study 45 days prior to submission for publication/presentation. If there is disagreement concerning appropriateness of the materials, Investigator and Sponsor must meet to make a good faith effort to discuss/resolve disagreement prior to submission for publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo/Asenapine n=44 participants at risk Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=157 participants at risk Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Gastrointestinal disorders Gastritis	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Metabolism and nutrition disorders Polydipsia	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Metabolism and nutrition disorders Water intoxication	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Musculoskeletal and connective tissue disorders Muscle rigidity	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Nervous system disorders Neuroleptic malignant syndrome	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Nervous system disorders Somnolence	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Abnormal behaviour	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Anxiety	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Completed suicide	2.3% 1/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.00% 0/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Depressed mood	2.3% 1/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.00% 0/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Depression	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Irritability	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Panic attack	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Restlessness	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Schizophrenia	9.1% 4/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	14.0% 22/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Sleep disorder	2.3% 1/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.00% 0/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Stress	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Suicidal ideation	0.00% 0/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	1.9% 3/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Vascular disorders Hypotension	2.3% 1/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.00% 0/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)

Measure	Placebo/Asenapine n=44 participants at risk Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability	Asenapine 5/10 mg BID n=157 participants at risk Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability
Cardiac disorders Palpitations	6.8% 3/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	1.3% 2/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Gastrointestinal disorders Constipation	9.1% 4/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	7.6% 12/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Gastrointestinal disorders Hypoaesthesia oral	9.1% 4/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Gastrointestinal disorders Stomatitis	9.1% 4/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	1.3% 2/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Infections and infestations Nasopharyngitis	13.6% 6/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	21.7% 34/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Investigations Aalanine aminotranferase increased	6.8% 3/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	5.1% 8/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Investigations Weight increased	15.9% 7/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	10.8% 17/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Metabolism and nutrition disorders Hyperlipidaemia	6.8% 3/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	1.9% 3/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Nervous system disorders Akathisia	4.5% 2/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	8.3% 13/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Nervous system disorders Dizziness	4.5% 2/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	5.7% 9/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Nervous system disorders Headache	20.5% 9/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	5.7% 9/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Nervous system disorders Somnolence	11.4% 5/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	10.8% 17/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Nervous system disorders Tremor	9.1% 4/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	3.8% 6/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Insomnia	4.5% 2/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	7.6% 12/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Psychiatric disorders Schizophrenia	13.6% 6/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	10.8% 17/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Reproductive system and breast disorders Dysmenorrhea	6.8% 3/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	0.64% 1/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Skin and subcutaneous tissue disorders Eczema	6.8% 3/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	3.2% 5/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Skin and subcutaneous tissue disorders Pruritus	6.8% 3/44 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)	2.5% 4/157 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)