- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01617187
A Study of the Efficacy and Safety of Asenapine in Participants With an Acute Exacerbation of Schizophrenia (P05688)
February 7, 2022 updated by: Organon and Co
A Multicenter, Randomized, Double-Blind, Fixed-Dose, 6-Week Trial of the Efficacy and Safety of Asenapine Compared With Placebo Using Olanzapine as an Active Control in Subjects With an Acute Exacerbation of Schizophrenia
The purpose of this trial is to assess the effect of asenapine 2.5 and 5 mg sublingually twice daily (BID) compared with placebo in the treatment of schizophrenia (overall symptoms) as measured by the Positive and Negative Syndrome Scale (PANSS).
Olanzapine administered 15 mg orally once daily (QD) was used as an active control.
The primary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by the change from Baseline in the PANSS total score at Day 42.
The first key secondary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by the change from Baseline in Clinical Global Impression Scale-Severity (CGI-S) score at Day 42.
The second key secondary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by the rate of PANSS responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The trial consists of a screening/tapering period, treatment period, and follow-up period.
The 6-week active treatment period includes an inpatient phase and outpatient phase.
Participants who complete the trial may continue treatment under a long-term extension protocol (P05689).
Participants who do not continue in the treatment continuation trial (whether they complete the 6-week trial or discontinue prematurely) will have a follow-up visit 7 days after their last dose of trial medication.
Study Type
Interventional
Enrollment (Actual)
360
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Current diagnosis of schizophrenia of paranoid, disorganized, or undifferentiated subtype
- Minimum PANSS total score of 70 at Screening and Baseline
- Score of at least 4 (moderate) in two or more of the five items in the positive subscale of the PANSS
- Confirmed to be experiencing an acute exacerbation of schizophrenia
- CGI-S scale score of at least 4 (moderately ill) at Baseline
- Has responded positively to an antipsychotic medication other than clozapine (Clozaril®) in a prior episode
Exclusion Criteria:
- Body mass index (BMI) <18.5 or >40.0 kg/m^2
- Laboratory and/or clinical evidence of clinically significant hepatic conditions
- Known history of, or undergoing treatment for, narrow angle glaucoma
- Diagnosed with epilepsy or has had any seizure disorder beyond childhood febrile seizures
- Known serological evidence of human immunodeficiency virus (HIV) antibody
- History of neuroleptic malignant syndrome or tardive dyskinesias
- Past or current diagnosis of schizoaffective disorder, schizophrenia of residual subtype, schizophrenia of catatonic subtype, current diagnosis of schizophrenia with course specifiers continuous, single episode in partial remission, or single episode in full remission, or borderline personality disorder
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo BID
|
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually
|
Experimental: Asenapine 2.5 mg BID
|
2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
|
Experimental: Asenapine 5 mg BID
|
2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
|
Active Comparator: Olanzapine 15 mg QD
|
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually
5 and 10 mg film-coated active olanzapine tablets administered orally QD.
The time of the active olanzapine dose (either morning or evening) is not disclosed in order to preserve blinding
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in PANSS Total Score at Day 42
Time Frame: Baseline and Day 42
|
The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms.
It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items).
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
The PANSS total score for each participant was sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms.
The reported measure is the change from baseline at Day 42; improvement in symptoms is represented by negative values.
|
Baseline and Day 42
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in CGI-S Score at Day 42
Time Frame: Baseline and Day 42
|
Change from baseline in CGI-S score at Day 42 is a Key Secondary Outcome Measure.
CGI-S is a 7-point scale for assessing the global severity of the participant's illness, with ratings from 1=normal, not ill to 7=very severely ill.
The reported measure is the change from baseline at Day 42; improvement in symptoms is represented by negative values.
|
Baseline and Day 42
|
Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42
Time Frame: Baseline and Day 42
|
Rate of PANSS responders at Day 42 is a Key Secondary Outcome Measure.
A PANSS responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS total score at a post-baseline assessment.
The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms.
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms.
Missing data were imputed by Last Observation Carried Forward (LOCF).
|
Baseline and Day 42
|
Change From Baseline in Body Weight at Day 42
Time Frame: Baseline and Day 42
|
Change from baseline in body weight at Day 42 is the Key Safety Outcome Measure.
|
Baseline and Day 42
|
Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35
Time Frame: Baseline and Days 4, 7, 14, 21, 28 and 35
|
The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms.
It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items).
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
The PANSS total score for each participant was sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms.
The reported measure is the change from baseline; improvement in symptoms is represented by negative values.
|
Baseline and Days 4, 7, 14, 21, 28 and 35
|
Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Days 4, 7, 14, 21, 28 and 35
Time Frame: Days 4, 7, 14, 21, 28 and 35
|
A PANSS responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS total score at a post-baseline assessment.
The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms.
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms.
Missing data were imputed by LOCF.
|
Days 4, 7, 14, 21, 28 and 35
|
Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35
Time Frame: Baseline and Days 4, 7, 14, 21, 28 and 35
|
CGI-S is a 7-point scale for assessing the global severity of the participant's illness, with ratings from 1=normal, not ill to 7=very severely ill.
The reported measure is the change from baseline; improvement in symptoms is represented by negative values.
|
Baseline and Days 4, 7, 14, 21, 28 and 35
|
Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42
Time Frame: Days 4, 7, 14, 21, 28, 35 and 42
|
A CGI-I responder was defined as a participant who had a CGI-I score of 1 (very much improved) or 2 (much improved) at a post-baseline assessment.
CGI-I is a 7-point scale for assessing the global improvement of the participant's illness relative to baseline, with ratings from 1=very much improved to 7=very much worse.
Missing data were imputed by LOCF.
|
Days 4, 7, 14, 21, 28, 35 and 42
|
Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42
Time Frame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
This measure reports results for the 7 items of the negative subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms.
Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal).
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
PANSS negative subscale score for each participant was sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Measure reports change from baseline; improvement in symptoms is represented by negative values.
|
Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42
Time Frame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
This measure reports results for the 7 items of the positive subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms.
Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions).
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
PANSS positive subscale score for each participant was sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Measure reports change from baseline; improvement in symptoms is represented by negative values.
|
Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42
Time Frame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
This measure reports results for the 16 items of the general psychopathology subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia.
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
The PANSS general psychopathology subscale score for each participant was calculated as the sum of the rating assigned to each of the 16 subscale items, and ranged from 16 to 112 with a higher score indicating greater severity of symptoms.
The reported measure is the change from baseline; improvement in symptoms is represented by negative values.
|
Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
Time Frame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
This measure reports results for the 8 items of the Marder positive symptom factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms.
Marder factors are a modified grouping of the 30 PANSS items.
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
PANSS Marder factor positive symptom score for each participant was sum of rating assigned to each of the 8 applicable Marder factor items, and ranged from 8 to 56 with a higher score indicating greater severity of symptoms.
Measure reports change from baseline; improvement in symptoms is represented by negative values.
|
Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
Time Frame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
This measure reports results for the 7 items of the Marder negative symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms.
Marder factors are a modified grouping of the 30 PANSS items.
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
PANSS Marder factor negative symptom score for each participant was sum of the rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Measure reports change from baseline; improvement in symptoms is represented by negative values.
|
Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
Time Frame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
This measure reports results for the 7 items of the Marder disorganized thoughts factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms.
Marder factors are a modified grouping of the 30 PANSS items.
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
PANSS Marder factor disorganized thought symptom score for each participant was sum of rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Measure reports change from baseline; improvement in symptoms is represented by negative values.
|
Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
Time Frame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
This measure reports results for the 4 items of the Marder hostility/excitement factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms.
Marder factors are a modified grouping of the 30 PANSS items.
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
PANSS Marder factor hostility/excitement symptom score for each participant was sum of rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms.
Measure reports change from baseline; improvement in symptoms is represented by negative values.
|
Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
Time Frame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
This measure reports results for the 4 items of the Marder anxiety/depression factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms.
Marder factors are a modified grouping of the 30 PANSS items.
For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme.
PANSS Marder factor anxiety/depression symptom score for each participant was sum of rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms.
Measure reports change from baseline; improvement in symptoms is represented by negative values.
|
Baseline and Days 4, 7, 14, 21, 28, 35 and 42
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 4, 2012
Primary Completion (Actual)
August 11, 2014
Study Completion (Actual)
September 9, 2014
Study Registration Dates
First Submitted
June 8, 2012
First Submitted That Met QC Criteria
June 8, 2012
First Posted (Estimate)
June 12, 2012
Study Record Updates
Last Update Posted (Actual)
February 9, 2022
Last Update Submitted That Met QC Criteria
February 7, 2022
Last Verified
February 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Schizophrenia Spectrum and Other Psychotic Disorders
- Schizophrenia
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiemetics
- Gastrointestinal Agents
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Olanzapine
- Asenapine
Other Study ID Numbers
- P05688
- 2010-018407-28 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Study Data/Documents
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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