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A Study of the Efficacy and Safety of Asenapine in Participants With an Acute Exacerbation of Schizophrenia (P05688)

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ClinicalTrials.gov Identifier: NCT01617187
Recruitment Status : Completed
First Posted : June 12, 2012
Results First Posted : August 31, 2015
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE June 8, 2012
First Posted Date  ICMJE June 12, 2012
Results First Submitted Date  ICMJE July 31, 2015
Results First Posted Date  ICMJE August 31, 2015
Last Update Posted Date October 11, 2018
Actual Study Start Date  ICMJE December 4, 2012
Actual Primary Completion Date August 11, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2015)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 8, 2012)
Change From Baseline to Day 42 in Positive and Negative Syndrome Scale (PANSS) Total Score [ Time Frame: Baseline, Day 42 ]
PANSS is a 30-item instrument for assessing symptoms of schizophrenia composed of 3 subscales: Positive (7 items), Negative (7 items), and General Psychopathology (16 items). Symptoms rated 1-7 points (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate-severe, 6=severe, and 7=extreme) representing increasing levels of psychopathology. Minimum scores for Positive, Negative, and General subscales= 7, 7, and 16 points respectively; minimum total score=30 points. Maximum scores for Positive, Negative, and General subscales=49, 49 and 112 respectively; maximum total score=210 points
Change History Complete list of historical versions of study NCT01617187 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2015)
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2012)
  • Change from Baseline to Day 42 in Clinical Global Impression - Severity of Illness (CGI-S) Score [ Time Frame: Baseline, Day 42 ]
    The CGI-S scale is a clinical instrument which rates the overall severity of any mental disorder and refers to the global impression of the patient. It is rated according to the clinical judgement of the physician in routine professional practice on a scale for the overall current severity of symptoms from 1 (healthy, not ill) to 7 (among the most severely ill).
  • Number of Participants with ≥30% Reduction in PANSS Total Score (Responders) at Day 42 [ Time Frame: Baseline to Day 42 ]
    PANSS is a 30-item instrument for assessing symptoms of schizophrenia composed of 3 subscales: Positive (7 items), Negative (7 items), and General Psychopathology (16 items). Symptoms rated 1-7 points (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate-severe, 6=severe, and 7=extreme) representing increasing levels of psychopathology. Minimum scores for Positive, Negative, and General subscales= 7, 7, and 16 points respectively; minimum total score=30 points. Maximum scores for Positive, Negative, and General subscales=49, 49 and 112 respectively; maximum total score=210 points
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Efficacy and Safety of Asenapine in Participants With an Acute Exacerbation of Schizophrenia (P05688)
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Schizophrenia
Intervention  ICMJE
  • Drug: Asenapine
    2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually
  • Drug: Placebo Asenapine
    Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually
  • Drug: Olanzapine
    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
  • Drug: Placebo Olanzapine
    Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
Study Arms  ICMJE
  • Experimental: Asenapine 2.5 mg BID
    Interventions:
    • Drug: Asenapine
    • Drug: Placebo Olanzapine
  • Experimental: Asenapine 5 mg BID
    Interventions:
    • Drug: Asenapine
    • Drug: Placebo Olanzapine
  • Active Comparator: Olanzapine 15 mg QD
    Interventions:
    • Drug: Placebo Asenapine
    • Drug: Olanzapine
    • Drug: Placebo Olanzapine
  • Placebo Comparator: Placebo BID
    Interventions:
    • Drug: Placebo Asenapine
    • Drug: Placebo Olanzapine
Publications * Landbloom R, Mackle M, Wu X, Kelly L, Snow-Adami L, McIntyre RS, Mathews M, Hundt C. Asenapine for the treatment of adults with an acute exacerbation of schizophrenia: results from a randomized, double-blind, fixed-dose, placebo-controlled trial with olanzapine as an active control. CNS Spectr. 2017 Aug;22(4):333-341. doi: 10.1017/S1092852916000377. Epub 2016 Nov 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 25, 2014)
360
Original Estimated Enrollment  ICMJE
 (submitted: June 8, 2012)
354
Actual Study Completion Date  ICMJE September 9, 2014
Actual Primary Completion Date August 11, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Bulgaria,   Croatia,   Romania,   Russian Federation,   Ukraine,   United States
 
Administrative Information
NCT Number  ICMJE NCT01617187
Other Study ID Numbers  ICMJE P05688
2010-018407-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP