Trial Outcomes & Findings for Long-Term Efficacy and Safety of Asenapine Using Haloperidol as a Positive Control (41513)(COMPLETED)(P05785) (NCT NCT00156065)

Last Updated: 2022-02-08

Results Overview

Loss of effect in subjects who had \>=30% decrease from baseline in Positive and Negative Syndrome Scale (PANSS) score at the end of the original trial (NCT00156104) preceding the long-term extension. PANSS is a 30-item clinician-rated instrument for assessing symptoms of schizophrenia. Scores range from 30-210; higher scores indicate greater severity. Loss of effect = increase in total PANSS \>=30% from start of current study; subjective worsening of schizophrenia/request for dose increase; Clinical Global Impressions of Severity of Illness score \>=6; discontinuation for lack of efficacy.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

187 participants

Primary outcome timeframe

Throughout the 52 weeks of the trial.

Results posted on

2022-02-08

Participant Flow

Note that one participant in each of the Placebo/Asenapine and Asenapine/Asenapine groups was enrolled but did not receive treatment. Thus, the numbers who started the period will be greater than the numbers presented at baseline and for analysis.

Participant milestones

Participant milestones
Measure	Placebo/Asenapine Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension	Asenapine/Asenapine Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension	Haloperidol/Haloperidol Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension
Overall Study STARTED	51	93	43
Overall Study COMPLETED	20	30	16
Overall Study NOT COMPLETED	31	63	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Asenapine Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension	Asenapine/Asenapine Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension	Haloperidol/Haloperidol Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension
Overall Study Enrolled But Never Received Treatment	1	1	0
Overall Study Adverse Event	8	11	4
Overall Study Lack of Efficacy	2	9	3
Overall Study Withdrawal by Subject	13	26	16
Overall Study Lost to Follow-up	5	7	1
Overall Study Other	2	9	3

Baseline Characteristics

Long-Term Efficacy and Safety of Asenapine Using Haloperidol as a Positive Control (41513)(COMPLETED)(P05785)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Asenapine n=50 Participants Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension	Asenapine/Asenapine n=92 Participants Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension	Haloperidol/Haloperidol n=43 Participants Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension	Total n=185 Participants Total of all reporting groups
Age, Continuous	41.3 years STANDARD_DEVIATION 12.6 • n=5 Participants	35.3 years STANDARD_DEVIATION 10.4 • n=7 Participants	39.9 years STANDARD_DEVIATION 11.6 • n=5 Participants	38.0 years STANDARD_DEVIATION 11.6 • n=4 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	37 Participants n=7 Participants	25 Participants n=5 Participants	84 Participants n=4 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	55 Participants n=7 Participants	18 Participants n=5 Participants	101 Participants n=4 Participants

PRIMARY outcome

Timeframe: Throughout the 52 weeks of the trial.

Population: These are participants who completed the original acute-phase trial (41023) with a decrease from baseline in Positive and Negative Syndrome Scale (PANSS) score \>= 30%, received at least one dose in the current long-term extension, and had at least one post-baseline PANSS assessment during the extension.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=30 Participants Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension	Asenapine/Asenapine n=65 Participants Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension	Haloperidol/Haloperidol n=29 Participants Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension
Loss of Effect Over Time <=Week 1	7 Participants	15 Participants	6 Participants
Loss of Effect Over Time >Week 1 to Week 2	3 Participants	4 Participants	4 Participants
Loss of Effect Over Time >Week 2 to Week 4	1 Participants	14 Participants	3 Participants
Loss of Effect Over Time >Week 4 to Week 8	3 Participants	3 Participants	1 Participants
Loss of Effect Over Time >Week 8 to Week 12	2 Participants	1 Participants	1 Participants
Loss of Effect Over Time >Week 12 to Week 16	3 Participants	1 Participants	4 Participants
Loss of Effect Over Time >Week 16 to Week 20	0 Participants	1 Participants	1 Participants
Loss of Effect Over Time >Week 20 to Week 24	0 Participants	3 Participants	0 Participants
Loss of Effect Over Time >Week 24 to Week 28	0 Participants	1 Participants	0 Participants
Loss of Effect Over Time >Week 28 to Week 32	1 Participants	3 Participants	1 Participants
Loss of Effect Over Time >Week 32 to Week 36	0 Participants	0 Participants	0 Participants
Loss of Effect Over Time >Week 36 to Week 40	0 Participants	0 Participants	1 Participants
Loss of Effect Over Time >Week 40 to Week 44	0 Participants	0 Participants	0 Participants
Loss of Effect Over Time >Week 44 to Week 48	0 Participants	0 Participants	0 Participants
Loss of Effect Over Time >Week 48 to Week 52	2 Participants	5 Participants	2 Participants

PRIMARY outcome

Timeframe: 52 Weeks

Kaplan-Meier estimate of median time to loss of effect in subjects who had \>=30% decrease from baseline in PANSS score at the end of the original trial (NCT00156104) preceding the long-term extension. PANSS is a 30-item clinician-rated instrument for assessing symptoms of schizophrenia. Scores range from 30-210; higher scores indicate greater severity. Loss of effect = increase in total PANSS \>=30% from start of current study; subjective worsening of schizophrenia/request for dose increase; Clinical Global Impressions of Severity of Illness score \>=6; discontinuation for lack of efficacy.

Outcome measures

Outcome measures
Measure	Placebo/Asenapine n=30 Participants Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension	Asenapine/Asenapine n=65 Participants Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension	Haloperidol/Haloperidol n=29 Participants Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension
Median Survival Time of Effect	57 Days Interval 15.0 to 111.0	31 Days Interval 28.0 to 140.0	85 Days Interval 15.0 to 118.0

Adverse Events

Placebo/Asenapine

Serious events: 12 serious events

Other events: 28 other events

Deaths: 0 deaths

Asenapine/Asenapine

Serious events: 13 serious events

Other events: 54 other events

Deaths: 0 deaths

Haloperidol/Haloperidol

Serious events: 6 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo/Asenapine n=50 participants at risk Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension	Asenapine/Asenapine n=92 participants at risk Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension	Haloperidol/Haloperidol n=43 participants at risk Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension
Injury, poisoning and procedural complications DRUG EXPOSURE DURING PREGNANCY	2.0% 1/50 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	1.1% 1/92 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/43 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Injury, poisoning and procedural complications MULTIPLE FRACTURES	0.00% 0/50 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	1.1% 1/92 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/43 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Injury, poisoning and procedural complications ROAD TRAFFIC ACCIDENT	0.00% 0/50 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	1.1% 1/92 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/43 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Metabolism and nutrition disorders HYPONATREMIA	0.00% 0/50 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/92 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Nervous system disorders CONVULSION	0.00% 0/50 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/92 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	2.3% 1/43 • Number of events 2 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Nervous system disorders SYNCOPE	2.0% 1/50 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/92 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/43 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Psychiatric disorders AGITATION	0.00% 0/50 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	1.1% 1/92 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/43 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Psychiatric disorders COMPLETED SUICIDE	0.00% 0/50 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	1.1% 1/92 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/43 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Psychiatric disorders SCHIZOPHRENIA	14.0% 7/50 • Number of events 8 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	8.7% 8/92 • Number of events 14 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	11.6% 5/43 • Number of events 6 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Psychiatric disorders SCHIZOPHRENIA, PARANOID TYPE	6.0% 3/50 • Number of events 3 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	1.1% 1/92 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/43 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Psychiatric disorders SUICIDAL IDEATION	0.00% 0/50 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	1.1% 1/92 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/43 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Psychiatric disorders SUICIDE ATTEMPT	0.00% 0/50 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/92 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	0.00% 0/50 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/92 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.
Surgical and medical procedures ABORTION INDUCED	2.0% 1/50 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	1.1% 1/92 • Number of events 1 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.	0.00% 0/43 • Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up. Information regarding AEs was obtained by questioning or examining the subject at each visit, and recording complaints and symptoms. Reports are for all serious AEs and treatment-emergent nonserious AEs.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Except for compelling legal reasons, neither the sponsor nor the investigator will communicate to third parties any result of the clinical trial before the CTR has been released by the sponsor.
Publication restrictions are in place

Restriction type: OTHER