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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01617187
First received: June 8, 2012
Last updated: July 31, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Asenapine
Drug: Placebo Asenapine
Drug: Olanzapine
Drug: Placebo Olanzapine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change From Baseline in PANSS Total Score at Day 42 [ Time Frame: Baseline and Day 42 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in CGI-S Score at Day 42 [ Time Frame: Baseline and Day 42 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 360
Study Start Date: December 2012
Study Completion Date: September 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Asenapine 2.5 mg BID Drug: Asenapine
2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually
Drug: Placebo Olanzapine
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
Experimental: Asenapine 5 mg BID Drug: Asenapine
2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually
Drug: Placebo Olanzapine
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
Active Comparator: Olanzapine 15 mg QD 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
Placebo Comparator: Placebo BID Drug: Placebo Asenapine
Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually
Drug: Placebo Olanzapine
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617187

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01617187     History of Changes
Other Study ID Numbers: P05688, 2010-018407-28
Study First Received: June 8, 2012
Results First Received: July 31, 2015
Last Updated: July 31, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Asenapine
Olanzapine
Antiemetics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on September 02, 2015