Fixed Dose Efficacy and Safety Study of Asenapine for the Treatment of Schizophrenia in Adolescents (P05896)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01190254
First received: August 25, 2010
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

This study is designed to evaluate whether asenapine, which is approved by the United States Food and Drug Administration (US FDA) for acute treatment of schizophrenia in adults, is also effective in adolescents with schizophrenia. Participants who qualify for the study will be randomly assigned to receive a fixed dose of asenapine (either 2.5 mg or 5 mg twice daily [BID]) or placebo for 8 weeks. Throughout the study, observations will be made on each participant at various times to assess the efficacy and safety of the study treatment. The primary objective of the trial is to demonstrate significant superiority of at least one asenapine dose to placebo, as measured by the change from baseline of the Positive and Negative Syndrome Scale (PANSS) total score at Day 56.


Condition Intervention Phase
Schizophrenia, Paranoid
Schizophrenia, Disorganized
Schizophrenia, Undifferentiated
Drug: asenapine 2.5 mg
Drug: asenapine 5.0 mg
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An 8-week, Placebo-controlled, Double-blind, Randomized, Fixed-dose Efficacy and Safety Trial of Asenapine in Adolescent Subjects With Schizophrenia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ Designated as safety issue: No ]
    The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). 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. The PANSS total score for each participant was calculated as the 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 56; improvement in symptoms is represented by negative values.


Secondary Outcome Measures:
  • Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ Designated as safety issue: No ]
    Change from baseline in CGI-S score at Day 56 is the 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 56; improvement in symptoms is represented by negative values.

  • Change From Baseline in PANSS Positive Subscale Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ 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 the symptoms of schizophrenia. 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. The PANSS positive subscale score for each participant was calculated as the 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. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

  • Change From Baseline in PANSS Negative Subscale Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ 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 the symptoms of schizophrenia. 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. The PANSS negative subscale score for each participant was calculated as the 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. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

  • Change From Baseline in PANSS Positive and Negative Subscale Scores Combined at Day 56 [ Time Frame: Baseline and Day 56 ] [ Designated as safety issue: No ]
    This measure reports results for the combined positive subscale (7 items) and negative subscale (7 items) of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each of the total 14 items in the combined positive and negative subscales, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive and negative subscale scores combined for each participant was calculated as the sum of the rating assigned to each of the 14 combined subscale items, and ranged from 14 to 98 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

  • Change From Baseline in PANSS General Psychopathology Subscale Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ 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 at Day 56; improvement in symptoms is represented by negative values.

  • Change From Baseline in PANSS Marder Positive Symptoms Factor Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ Designated as safety issue: No ]
    This measure reports results for the 8 items of the Marder positive symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items (Marder et al. J Clin Psychiatry 1997;58(12):538-46). 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. The PANSS Marder positive symptoms factor score for each participant was calculated as the sum of the 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. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

  • Change From Baseline in PANSS Marder Negative Symptoms Factor Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ 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 the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. 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. The PANSS Marder negative symptoms factor score for each participant was calculated as the 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. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

  • Change From Baseline in PANSS Marder Disorganized Thoughts Factor Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ 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 the symptoms of schizophrenia. 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. The PANSS Marder disorganized thoughts factor score for each participant was calculated as the 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. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

  • Change From Baseline in PANSS Marder Hostility/Excitement Factor Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ 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 the symptoms of schizophrenia. 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. The PANSS Marder hostility/excitement factor score for each participant was calculated as the sum of the 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. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

  • Change From Baseline in PANSS Marder Anxiety/Depression Factor Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ 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 the symptoms of schizophrenia. 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. The PANSS Marder anxiety/depression factor score for each participant was calculated as the sum of the 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. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

  • Total PANSS 30% Responders [ Time Frame: Baseline up to Day 56 ] [ Designated as safety issue: No ]
    A Total PANSS 30% responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS Total score at the last available assessment of the study for that participant (i.e., endpoint). The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. 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.

  • Kaplan-Meier Estimate of Cumulative Percentage of Participants With Total PANSS 30% Response at End of Study [ Time Frame: Baseline up to approximately Day 59 ] [ Designated as safety issue: No ]
    A total PANSS 30% response was defined as a reduction from baseline of at least 30% in the PANSS Total score. The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. 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. The Kaplan-Meier estimate reports the cumulative percentage of participants with total PANSS 30% response from first drug intake up to approximately Day 59.

  • Clinical Global Impression of Improvement (CGI-I) Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ Designated as safety issue: No ]
    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.

  • CGI-I Responders [ Time Frame: Baseline up to Day 56 ] [ 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 the last available assessment of the study for that participant (i.e., endpoint). 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.

  • Kaplan-Meier Estimate of Cumulative Percentage of Participants With CGI-I Response at End of Study [ Time Frame: Baseline up to approximately Day 58 ] [ Designated as safety issue: No ]
    CGI-I response was defined as the occurrence of a CGI-I score of 1 (very much improved) or 2 (much improved). 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. The Kaplan-Meier estimate reports the cumulative percentage of participants with CGI-I response from first drug intake up to approximately Day 58.

  • Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ Designated as safety issue: No ]
    CGAS is a 100-point scale measuring psychological, social, and school functioning in children aged 6-17. Minimum scores ranged from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The reported measure is the change from baseline at Day 56; improvement in functioning is represented by positive values.

  • Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 56 [ Time Frame: Baseline and Day 56 ] [ Designated as safety issue: No ]
    PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant was calculated as the sum of the rating assigned to each of the first 14 items, and ranged from 14 to 70 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 56; improvement in quality of life is represented by positive values. This analysis used a last-observation-carried-forward (LOCF) approach; if no Day 56 value was available for a participant, the last available assessment prior to the Day 56 assessment was used.

  • Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 56 [ Time Frame: Baseline and Day 56 ] [ Designated as safety issue: No ]
    PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The Item 15 result is defined to be the PQ-LES-Q overall score, and ranged from 1 to 5 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 56; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 56 value was available for a participant, the last available assessment prior to the Day 56 assessment was used.


Enrollment: 306
Study Start Date: September 2010
Study Completion Date: April 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Asenapine 2.5 mg BID
Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks.
Drug: asenapine 2.5 mg
asenapine 2.5 mg tablets for sublingual administration
Other Name: Saphris®, SCH 900274, Org 5222
Experimental: Asenapine 5.0 mg BID
Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period.
Drug: asenapine 2.5 mg
asenapine 2.5 mg tablets for sublingual administration
Other Name: Saphris®, SCH 900274, Org 5222
Drug: asenapine 5.0 mg
asenapine 5.0 mg tablets for sublingual administration
Other Name: Saphris®, SCH 900274, Org 5222
Placebo Comparator: Placebo
Participants receive placebo asenapine tablets sublingually BID for 8 weeks.
Drug: placebo
asenapine-matched placebo tablets for sublingual administration

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Each participant must have schizophrenia, diagnosed and confirmed by board-eligible or board certified psychiatrists with at least two years of specialization in pediatric/adolescent psychiatric medicine.
  • Each participant must be ≥12 years of age and <18 years of age.
  • Each participant must have a minimum PANSS total score of 80 at Screening and Baseline.
  • Each participant must have a score of at least 4 (moderate) on two or more of the five items in the positive subscale of the PANSS (delusions, conceptual disorganization, hallucinatory behavior, grandiosity, suspiciousness/ persecution) at Screening and Baseline.
  • Each participant must have a CGI-S scale score of ≥4 at Screening and Baseline.
  • Each participant must taper off all prohibited psychotropic medications (including antipsychotics, antidepressants, and mood stabilizers) prior to Baseline.
  • Each participant must agree not to begin formal, structured psychotherapy during the trial.

Exclusion Criteria:

  • A participant must not have a diagnosis of schizoaffective disorder; schizophrenia of residual subtype; schizophrenia of catatonic subtype, or schizophrenia with "continuous," "single episode in partial remission," or "single episode in full remission" course specifiers.
  • A participant must not have a primary Axis I diagnosis other than schizophrenia and must not have a comorbid Axis I diagnosis that is primarily responsible for current symptoms and functional impairment.
  • A participant must not have a known or suspected diagnosis of mental retardation or organic brain disorder.
  • A participant must not currently (within the past 6 months) meet the Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM-IV-TR^TM) criteria for substance abuse or dependence (excluding nicotine).
  • A participant must not have a diagnosis of psychotic disorder or a behavioral disturbance thought to be substance induced or due to substance abuse.
  • A participant must not be at imminent risk of self-harm or harm to others, in the investigator's opinion based on clinical interview and responses provided on the Columbia Suicide Severity Rating Scale (C-SSRS).
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01190254     History of Changes
Other Study ID Numbers: P05896, 2009-017971-10, MK-8274-020, CTRI/2011/07/001909
Study First Received: August 25, 2010
Results First Received: March 10, 2014
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Asenapine
adolescents
schizophrenia
phase IIIb
placebo-controlled

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia, Disorganized
Schizophrenia, Paranoid
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Asenapine
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 23, 2014