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

Sponsor
Organon and Co (Industry)
Overall Status
Completed
CT.gov ID
NCT00156065
Collaborator
(none)
187
3
25

Study Details

Study Description

Brief Summary

Schizophrenia is a brain disease. The primary features of schizophrenia are characterized by Positive symptoms (symptoms that should not be there, inability to think clearly, to distinguish reality from fantasy i.e., hearing voices) and Negative symptoms (a reduction or absence of normal behaviors or emotions, i.e., unable to manage emotions, make decisions and relate to others). Other symptoms include reduced ability to recall and learn new information, difficulty with problem solving, or maintaining productive employment. The symptoms of schizophrenia may be due to an imbalance in chemicals in the brain, primarily dopamine and serotonin, which enables brain cells to communicate with each other.

The clinical development of asenapine, as described in the 2007 IDB appears to have antipsychotic activity with superior symptomatic control compared to placebo and an improved safety profile compared to currently available neuroleptics. Its fast dissolving formulation may further add to treatment compliance. While various titration schedules have been used in previous studies, dose increases at 5 mg BID (twice daily) up to 10 mg BID have been well tolerated. Therefore, further exploration in a larger group of subjects with acute exacerbation of schizophrenia using an asenapine flexible dosing design ( 5 or 10 mg BID) will mimic actual clinical practice in a long-term 52-week extension trial.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
187 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Flexible-Dose, Long-Term Extension Trial of the Safety and Maintenance of Effect of Asenapine Using Haloperidol Positive Control in Subjects Who Complete Protocol 041023 [NCT00156104]
Study Start Date :
Sep 1, 2005
Actual Primary Completion Date :
Sep 1, 2007
Actual Study Completion Date :
Oct 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Haloperidol/Haloperidol

Haloperidol in original study (NCT00156104) and in current long-term extension.

Drug: Haloperidol
2-8 mg BID

Experimental: Asenapine/Asenapine

Asenapine in original study and asenapine in current long-term extension.

Drug: Asenapine
5 or 10 mg BID

Experimental: Placebo/Asenapine

Double-Blind subjects randomized to only placebo medication for 6 weeks in the short-term 041023 asenapine trial, were randomized (double-blind) into the long-term 041513 asenapine extension trial and received asenapine 5 mg BID for Week 1. After Week 1, subjects received asenapine (either 5 mg BID or 10 mg BID) for the remainder of the 52-week trial.

Drug: Asenapine
5 or 10 mg BID

Outcome Measures

Primary Outcome Measures

  1. Loss of Effect Over Time [Throughout the 52 weeks of the trial.]

    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.

  2. Median Survival Time of Effect [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Completed the short-term 041023 trial (NCT00156104)

  • Continued to meet all demographic and procedural inclusion criteria of the short-term trial upon entry into this long-term extension trial

  • Sign a written informed consent for the 041513 trial.

  • Demonstrated an acceptable degree of compliance with trial medication in the short-term trials in the opinion of the investigator

Exclusion Criteria:
  • CGI-S (Clinical Global Impressions of Severity of Illness) score of greater than or equal to 6 (severely psychotic)

  • Occurrence(s) of AEs (adverse events) or other clinically significant findings that would prohibit their continuation

  • Met any of exclusion criteria regarding medical/psychiatric status listed in the 041023 short-term trial

  • Met exclusion criteria for medication status in short-term trials except for antidepressants and mood stabilizers.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Organon and Co
ClinicalTrials.gov Identifier:
NCT00156065
Other Study ID Numbers:
  • P05785
  • Hera;
  • 41513
First Posted:
Sep 12, 2005
Last Update Posted:
Feb 8, 2022
Last Verified:
Feb 1, 2022
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail 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.
Arm/Group Title Placebo/Asenapine Asenapine/Asenapine Haloperidol/Haloperidol
Arm/Group Description Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension
Period Title: Overall Study
STARTED 51 93 43
COMPLETED 20 30 16
NOT COMPLETED 31 63 27

Baseline Characteristics

Arm/Group Title Placebo/Asenapine Asenapine/Asenapine Haloperidol/Haloperidol Total
Arm/Group Description Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension Total of all reporting groups
Overall Participants 50 92 43 185
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
41.3
(12.6)
35.3
(10.4)
39.9
(11.6)
38.0
(11.6)
Sex: Female, Male (Count of Participants)
Female
22
44%
37
40.2%
25
58.1%
84
45.4%
Male
28
56%
55
59.8%
18
41.9%
101
54.6%

Outcome Measures

1. Primary Outcome
Title Loss of Effect Over Time
Description 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.
Time Frame Throughout the 52 weeks of the trial.

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Placebo/Asenapine Asenapine/Asenapine Haloperidol/Haloperidol
Arm/Group Description Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension
Measure Participants 30 65 29
<=Week 1
7
14%
15
16.3%
6
14%
>Week 1 to Week 2
3
6%
4
4.3%
4
9.3%
>Week 2 to Week 4
1
2%
14
15.2%
3
7%
>Week 4 to Week 8
3
6%
3
3.3%
1
2.3%
>Week 8 to Week 12
2
4%
1
1.1%
1
2.3%
>Week 12 to Week 16
3
6%
1
1.1%
4
9.3%
>Week 16 to Week 20
0
0%
1
1.1%
1
2.3%
>Week 20 to Week 24
0
0%
3
3.3%
0
0%
>Week 24 to Week 28
0
0%
1
1.1%
0
0%
>Week 28 to Week 32
1
2%
3
3.3%
1
2.3%
>Week 32 to Week 36
0
0%
0
0%
0
0%
>Week 36 to Week 40
0
0%
0
0%
1
2.3%
>Week 40 to Week 44
0
0%
0
0%
0
0%
>Week 44 to Week 48
0
0%
0
0%
0
0%
>Week 48 to Week 52
2
4%
5
5.4%
2
4.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Asenapine
Comments
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Kaplan-Meier Estimate of Loss of Effect
Estimated Value 0.8619
Confidence Interval () 95%
0.6912 to 0.9644
Parameter Dispersion Type:
Value:
Estimation Comments 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.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Asenapine/Asenapine
Comments
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Kaplan-Meier Estimate of Loss of Effect
Estimated Value 0.8834
Confidence Interval () 95%
0.7744 to 0.9550
Parameter Dispersion Type:
Value:
Estimation Comments 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.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Haloperidol/Haloperidol
Comments
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Kaplan-Meier Estimate of Loss of Effect
Estimated Value 0.9376
Confidence Interval () 95%
0.7631 to 0.9952
Parameter Dispersion Type:
Value:
Estimation Comments 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.
2. Primary Outcome
Title Median Survival Time of Effect
Description 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.
Time Frame 52 Weeks

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Placebo/Asenapine Asenapine/Asenapine Haloperidol/Haloperidol
Arm/Group Description Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension
Measure Participants 30 65 29
Median (95% Confidence Interval) [Days]
57
31
85

Adverse Events

Time Frame Adverse events (AEs) were monitored continually through 52 weeks of treatment and 1 month of posttreatment follow-up.
Adverse Event Reporting Description 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.
Arm/Group Title Placebo/Asenapine Asenapine/Asenapine Haloperidol/Haloperidol
Arm/Group Description Placebo in Original Study (NCT00156104) and Asenapine 5 or 10 mg BID (twice daily) in Current Long-Term Extension Asenapine 5 or 10 mg BID in Original Study and in Current Long-Term Extension Haloperidol 2-8 mg BID in Original Study and in Current Long-Term Extension
All Cause Mortality
Placebo/Asenapine Asenapine/Asenapine Haloperidol/Haloperidol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Placebo/Asenapine Asenapine/Asenapine Haloperidol/Haloperidol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 12/50 (24%) 13/92 (14.1%) 6/43 (14%)
Injury, poisoning and procedural complications
DRUG EXPOSURE DURING PREGNANCY 1/50 (2%) 1 1/92 (1.1%) 1 0/43 (0%) 0
MULTIPLE FRACTURES 0/50 (0%) 0 1/92 (1.1%) 1 0/43 (0%) 0
ROAD TRAFFIC ACCIDENT 0/50 (0%) 0 1/92 (1.1%) 1 0/43 (0%) 0
Metabolism and nutrition disorders
HYPONATREMIA 0/50 (0%) 0 0/92 (0%) 0 1/43 (2.3%) 1
Nervous system disorders
CONVULSION 0/50 (0%) 0 0/92 (0%) 0 1/43 (2.3%) 2
SYNCOPE 1/50 (2%) 1 0/92 (0%) 0 0/43 (0%) 0
Psychiatric disorders
AGITATION 0/50 (0%) 0 1/92 (1.1%) 1 0/43 (0%) 0
COMPLETED SUICIDE 0/50 (0%) 0 1/92 (1.1%) 1 0/43 (0%) 0
SCHIZOPHRENIA 7/50 (14%) 8 8/92 (8.7%) 14 5/43 (11.6%) 6
SCHIZOPHRENIA, PARANOID TYPE 3/50 (6%) 3 1/92 (1.1%) 1 0/43 (0%) 0
SUICIDAL IDEATION 0/50 (0%) 0 1/92 (1.1%) 1 0/43 (0%) 0
SUICIDE ATTEMPT 0/50 (0%) 0 0/92 (0%) 0 1/43 (2.3%) 1
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE 0/50 (0%) 0 0/92 (0%) 0 1/43 (2.3%) 1
Surgical and medical procedures
ABORTION INDUCED 1/50 (2%) 1 1/92 (1.1%) 1 0/43 (0%) 0
Other (Not Including Serious) Adverse Events
Placebo/Asenapine Asenapine/Asenapine Haloperidol/Haloperidol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 28/50 (56%) 54/92 (58.7%) 25/43 (58.1%)
Gastrointestinal disorders
CONSTIPATION 4/50 (8%) 5 4/92 (4.3%) 4 3/43 (7%) 3
HYPOAESTHESIA ORAL 3/50 (6%) 3 0/92 (0%) 0 0/43 (0%) 0
NAUSEA 3/50 (6%) 3 2/92 (2.2%) 2 6/43 (14%) 6
VOMITING 2/50 (4%) 2 3/92 (3.3%) 3 3/43 (7%) 4
General disorders
ASTHENIA 5/50 (10%) 10 7/92 (7.6%) 8 6/43 (14%) 6
Infections and infestations
INFLUENZA 3/50 (6%) 3 4/92 (4.3%) 4 3/43 (7%) 4
Investigations
ALANINE AMINOTRANSFERASE INCREASED 0/50 (0%) 0 6/92 (6.5%) 6 1/43 (2.3%) 1
WEIGHT DECREASED 2/50 (4%) 2 5/92 (5.4%) 6 0/43 (0%) 0
WEIGHT INCREASED 1/50 (2%) 1 3/92 (3.3%) 3 3/43 (7%) 3
Nervous system disorders
AKATHISIA 4/50 (8%) 6 6/92 (6.5%) 7 3/43 (7%) 5
DIZZINESS 3/50 (6%) 3 2/92 (2.2%) 4 1/43 (2.3%) 1
HEADACHE 9/50 (18%) 17 10/92 (10.9%) 13 7/43 (16.3%) 8
PARKINSONISM 3/50 (6%) 3 10/92 (10.9%) 14 3/43 (7%) 7
SOMNOLENCE 5/50 (10%) 5 4/92 (4.3%) 6 1/43 (2.3%) 1
TREMOR 2/50 (4%) 3 3/92 (3.3%) 3 4/43 (9.3%) 6
Psychiatric disorders
AGITATION 1/50 (2%) 2 7/92 (7.6%) 8 2/43 (4.7%) 3
ANXIETY 3/50 (6%) 6 7/92 (7.6%) 12 2/43 (4.7%) 2
DEPRESSION 1/50 (2%) 2 2/92 (2.2%) 2 3/43 (7%) 3
INSOMNIA 12/50 (24%) 15 17/92 (18.5%) 34 4/43 (9.3%) 4
SCHIZOPHRENIA 5/50 (10%) 5 9/92 (9.8%) 11 3/43 (7%) 4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title Senior Vice President, Global Clinical Development
Organization Merck Sharp & Dohme Corp
Phone
Email ClinicalTrialsDisclosure@merck.com
Responsible Party:
Organon and Co
ClinicalTrials.gov Identifier:
NCT00156065
Other Study ID Numbers:
  • P05785
  • Hera;
  • 41513
First Posted:
Sep 12, 2005
Last Update Posted:
Feb 8, 2022
Last Verified:
Feb 1, 2022