Efficacy and Safety of Asenapine Compared With Olanzapine in Patients With Persistent Negative Symptoms of Schizophrenia (A7501013)(COMPLETED)(P05771)
Study Details
Study Description
Brief Summary
Treatment with conventional antipsychotics such as haloperidol has little effect or may sometimes even worsen negative symptoms (such as blunted affect, emotional withdrawal, and poor rapport) of schizophrenia. The newer "atypical" antipsychotics agents, such as olanzapine, has shown improvement in the treatment of negative symptoms in acute trials. The purpose of this study is to compare an investigational compound (asenapine) with a marketed agent (olanzapine) in the treatment of stable subjects with persistent negative symptoms of schizophrenia for 6 months. Patients completing this study may be eligible to participate in an extension 6 months of treatment. Patients are required to have stable symptoms prior to entry into study.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: asenapine
|
Drug: Asenapine
5-10 mg sublingually twice daily for up to 26 weeks
|
Active Comparator: olanzapine
|
Drug: Olanzapine
5-20 mg by mouth once daily for up to 26 weeks
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Negative Symptoms of Schizophrenia Measured by the Negative Symptom Assessment (NSA) Scale Total Score [Day 182]
The NSA Scale is a 16-item clinician-rated instrument for rating the negative symptomatology of schizophrenia. Total score ranges from 16 to 96, with greater scores indicating greater severity of symptoms.
Secondary Outcome Measures
- Change From Baseline in Quality of Life Measured by the Quality of Life Scale (QLS) Total Score [Day 182]
The Quality of Life Scale is a 21-item clinician-rated scale for rating psychosocial functioning (Interpersonal Relations, Instrumental Role, Intrapsychic Foundations, and Common Objects and Activities). The score ranges from 0 to 126, with greater values indicating better quality of life.
- Change From Baseline in Body Weight [Day 182]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Have a documented current diagnosis of schizophrenia of paranoid, disorganized, catatonic, residual, or undifferentiated subtype with persistent negative symptoms.
-
No increase in level of psychiatric care during the past few months due to worsening of symptoms of schizophrenia.
-
Caregiver required.
Exclusion Criteria:
-
Have an uncontrolled, unstable clinically significant medical condition.
-
Have any other psychiatric disorder other than schizophrenia as a primary diagnosis including depression.
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.- P05771
- Aphrodite
- A7501013
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Asenapine | Olanzapine |
---|---|---|
Arm/Group Description | 5-10 mg sublingually twice daily for up to 26 weeks | 5-20 mg by mouth once daily for up to 26 weeks |
Period Title: Overall Study | ||
STARTED | 244 | 224 |
COMPLETED | 121 | 143 |
NOT COMPLETED | 123 | 81 |
Baseline Characteristics
Arm/Group Title | Asenapine | Olanzapine | Total |
---|---|---|---|
Arm/Group Description | 5-10 mg sublingually twice daily for up to 26 weeks | 5-20 mg by mouth once daily for up to 26 weeks | Total of all reporting groups |
Overall Participants | 244 | 224 | 468 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
43.1
(11.43)
|
42.8
(11.27)
|
42.9
(11.34)
|
Age, Customized (participants) [Number] | |||
<18 years |
0
0%
|
0
0%
|
0
0%
|
18 to 64 years |
239
98%
|
217
96.9%
|
456
97.4%
|
>=65 years |
5
2%
|
7
3.1%
|
12
2.6%
|
Sex: Female, Male (Count of Participants) | |||
Female |
68
27.9%
|
54
24.1%
|
122
26.1%
|
Male |
176
72.1%
|
170
75.9%
|
346
73.9%
|
Body Weight (kg) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [kg] |
84.0
(19.01)
|
85.7
(18.71)
|
84.8
(18.86)
|
Outcome Measures
Title | Change From Baseline in Negative Symptoms of Schizophrenia Measured by the Negative Symptom Assessment (NSA) Scale Total Score |
---|---|
Description | The NSA Scale is a 16-item clinician-rated instrument for rating the negative symptomatology of schizophrenia. Total score ranges from 16 to 96, with greater scores indicating greater severity of symptoms. |
Time Frame | Day 182 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was intent to treat - subjects who received at least 1 dose of double-blind trial medication and had at least 1 post-baseline value. |
Arm/Group Title | Asenapine | Olanzapine |
---|---|---|
Arm/Group Description | 5-10 mg sublingually twice daily for up to 26 weeks | 5-20 mg by mouth once daily for up to 26 weeks |
Measure Participants | 234 | 218 |
Baseline |
60.4
(0.80)
|
61.3
(0.80)
|
Change From Baseline at Day 182 |
-9.7
(0.95)
|
-9.2
(0.89)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Asenapine, Olanzapine |
---|---|---|
Comments | The null hypothesis was that there was no difference in change from baseline in NSA Scale total score between asenapine and olanzapine at Day 182. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.7177 |
Comments | The test of hypothesis was a 2-tailed test with alpha=0.05 (0.049 to adjust for one interim analysis). | |
Method | Mixed Model for Repeated Measurements | |
Comments |
Title | Change From Baseline in Quality of Life Measured by the Quality of Life Scale (QLS) Total Score |
---|---|
Description | The Quality of Life Scale is a 21-item clinician-rated scale for rating psychosocial functioning (Interpersonal Relations, Instrumental Role, Intrapsychic Foundations, and Common Objects and Activities). The score ranges from 0 to 126, with greater values indicating better quality of life. |
Time Frame | Day 182 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was intent to treat - subjects who received at least 1 dose of double-blind trial medication and had at least 1 post-baseline value. |
Arm/Group Title | Asenapine | Olanzapine |
---|---|---|
Arm/Group Description | 5-10 mg sublingually twice daily for up to 26 weeks | 5-20 mg by mouth once daily for up to 26 weeks |
Measure Participants | 234 | 218 |
Baseline |
46.3
(1.20)
|
44.2
(1.20)
|
Change From Baseline at Day 182 |
11.1
(1.54)
|
7.1
(1.41)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Asenapine, Olanzapine |
---|---|---|
Comments | The null hypothesis was that there was no difference in change from baseline in QLS total score between asenapine and olanzapine at Day 182. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0565 |
Comments | The test of hypothesis was a 2-tailed test with alpha=0.025 nominal significance using the Bonferroni adjustment to account for multiplicity of the key secondary comparisons. | |
Method | Mixed Model for Repeated Measurements | |
Comments |
Title | Change From Baseline in Body Weight |
---|---|
Description | |
Time Frame | Day 182 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was intent to treat - subjects who received at least 1 dose of double-blind trial medication and had at least 1 post-baseline value. |
Arm/Group Title | Asenapine | Olanzapine |
---|---|---|
Arm/Group Description | 5-10 mg sublingually twice daily for up to 26 weeks | 5-20 mg by mouth once daily for up to 26 weeks |
Measure Participants | 234 | 218 |
Baseline |
84.2
(1.40)
|
84.7
(1.40)
|
Change From Baseline at Day 182 |
0.0
(0.43)
|
2.6
(0.40)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Asenapine, Olanzapine |
---|---|---|
Comments | The null hypothesis was that there was no difference in change from baseline in body weight between asenapine and olanzapine at Day 182. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | The test of hypothesis was a 2-tailed test with alpha=0.025 nominal significance using the Bonferroni adjustment to account for multiplicity of the key secondary comparisons. | |
Method | Mixed Model for Repeated Measurements | |
Comments |
Adverse Events
Time Frame | Adverse events (AEs) were recorded at each visit through end of treatment in this protocol (6 months). For subjects who did not continue in an extension protocol, serious adverse events (SAEs) were recorded via telephone 30 days after end of treatment. | |||
---|---|---|---|---|
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 SAEs and treatment-emergent nonserious AEs. | |||
Arm/Group Title | Asenapine | Olanzapine | ||
Arm/Group Description | 5-10 mg sublingually twice daily for up to 26 weeks | 5-20 mg by mouth once daily for up to 26 weeks | ||
All Cause Mortality |
||||
Asenapine | Olanzapine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Asenapine | Olanzapine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 30/244 (12.3%) | 18/224 (8%) | ||
Blood and lymphatic system disorders | ||||
PANCYTOPENIA | 0/244 (0%) | 0 | 1/224 (0.4%) | 1 |
Endocrine disorders | ||||
ATRIAL FIBRILLATION | 0/244 (0%) | 0 | 1/224 (0.4%) | 1 |
General disorders | ||||
VENTRICULAR EXTRASYSTOLES | 0/244 (0%) | 0 | 1/224 (0.4%) | 1 |
PYREXIA | 0/244 (0%) | 0 | 1/224 (0.4%) | 1 |
Hepatobiliary disorders | ||||
CHOLECYSTITIS CHRONIC | 1/244 (0.4%) | 1 | 0/224 (0%) | 0 |
CHOLELITHIASIS | 1/244 (0.4%) | 1 | 0/224 (0%) | 0 |
PORCELAIN GALLBLADDER | 1/244 (0.4%) | 1 | 0/224 (0%) | 0 |
Infections and infestations | ||||
BRONCHITIS | 1/244 (0.4%) | 1 | 0/224 (0%) | 0 |
CELLULITIS | 1/244 (0.4%) | 1 | 0/224 (0%) | 0 |
CLOSTRIDIUM DIFFICILE COLITIS | 0/244 (0%) | 0 | 1/224 (0.4%) | 1 |
Metabolism and nutrition disorders | ||||
DIABETES MELLITUS INADEQUATE CONTROL | 1/244 (0.4%) | 1 | 0/224 (0%) | 0 |
Nervous system disorders | ||||
GRAND MAL CONVULSION | 1/244 (0.4%) | 1 | 1/224 (0.4%) | 1 |
HEMORRHAGIC STROKE | 1/244 (0.4%) | 1 | 0/224 (0%) | 0 |
Psychiatric disorders | ||||
ALCOHOL ABUSE | 1/244 (0.4%) | 1 | 0/224 (0%) | 0 |
HOMICIDAL IDEATION | 1/244 (0.4%) | 1 | 1/224 (0.4%) | 1 |
PSYCHOTIC DISORDER | 4/244 (1.6%) | 4 | 1/224 (0.4%) | 1 |
SCHIZOPHRENIA | 11/244 (4.5%) | 11 | 10/224 (4.5%) | 11 |
SCHIZOPHRENIA, PARANOID TYPE | 8/244 (3.3%) | 8 | 6/224 (2.7%) | 6 |
SCHIZOPHRENIA, UNDIFFERENTIATED TYPE | 1/244 (0.4%) | 1 | 0/224 (0%) | 0 |
SUICIDAL IDEATION | 4/244 (1.6%) | 4 | 1/224 (0.4%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||
ASTHMA | 0/244 (0%) | 0 | 1/224 (0.4%) | 1 |
CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 1/244 (0.4%) | 1 | 0/224 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
Asenapine | Olanzapine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 145/244 (59.4%) | 140/224 (62.5%) | ||
Gastrointestinal disorders | ||||
DRY MOUTH | 9/244 (3.7%) | 9 | 18/224 (8%) | 20 |
NAUSEA | 20/244 (8.2%) | 23 | 11/224 (4.9%) | 12 |
Investigations | ||||
WEIGHT INCREASED | 23/244 (9.4%) | 23 | 48/224 (21.4%) | 51 |
Metabolism and nutrition disorders | ||||
INCREASED APPETITE | 8/244 (3.3%) | 8 | 12/224 (5.4%) | 16 |
Nervous system disorders | ||||
AKATHISIA | 22/244 (9%) | 29 | 13/224 (5.8%) | 16 |
DIZZINESS | 18/244 (7.4%) | 19 | 21/224 (9.4%) | 26 |
HEADACHE | 33/244 (13.5%) | 40 | 23/224 (10.3%) | 26 |
SEDATION | 16/244 (6.6%) | 17 | 17/224 (7.6%) | 19 |
SOMNOLENCE | 36/244 (14.8%) | 38 | 43/224 (19.2%) | 62 |
Psychiatric disorders | ||||
ANXIETY | 26/244 (10.7%) | 37 | 16/224 (7.1%) | 20 |
INSOMNIA | 43/244 (17.6%) | 55 | 26/224 (11.6%) | 34 |
Limitations/Caveats
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 clinical trial report has been released by the sponsor.
Results Point of Contact
Name/Title | Senior Vice President, Global Clinical Development |
---|---|
Organization | Merck Sharp & Dohme Corp. |
Phone | |
ClinicalTrialsDisclosure@merck.com |
- P05771
- Aphrodite
- A7501013