Fixed-dose Safety and Efficacy Study of Asenapine for the Treatment of Acute Manic or Mixed Episode in Bipolar 1 Disorder (P05691)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00764478
First received: September 30, 2008
Last updated: April 8, 2015
Last verified: April 2015
  Purpose

This trial will study the efficacy and safety of a fixed dose of asenapine in participants diagnosed with Bipolar 1 Disorder. Participants who qualify for the study will be randomly assigned to receive a fixed dose of asenapine (either 5 mg or 10 mg twice daily [BID]) or placebo (BID) for 3 weeks. Throughout the trial, observations will be made on each participant at various times to assess the safety and effectiveness of the study treatment. The primary hypothesis is that there is at least one dose of asenapine that is superior to placebo in the change from baseline in manic symptoms (as measured by Young Mania Rating Scale [YMRS]) at Day 21 of the trial.


Condition Intervention Phase
Bipolar 1 Disorder
Drug: Asenapine
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: A Phase 3b, Multicenter, Double-Blind, Fixed-Dose, Parallel-Group, Three Week Placebo Controlled Trial Evaluating the Safety and Efficacy of Asenapine in Subjects With Bipolar 1 Disorder Experiencing an Acute Manic or Mixed Episode (Protocol P05691 [Formerly 041044])

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score at Day 21 [ Time Frame: Baseline and Day 21 ] [ Designated as safety issue: No ]
    Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a mixed model repeated measures (MMRM) model. An improvement in symptoms is represented by change from baseline values that are negative.


Secondary Outcome Measures:
  • Change From Baseline in Clinical Global Impression - Bipolar Mania - Severity of Illness (CGI-BP-S) Overall Score at Day 21 [ Time Frame: Baseline and Day 21 ] [ Designated as safety issue: No ]
    The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Percentage of Participants Who Are Y-MRS Responders at Day 21 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by Last Observation Carried Forward (LOCF). Y-MRS responders are defined as having a >= 50% decrease from baseline in Y-MRS total score.

  • Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 [ Time Frame: Baseline and Day 2, Day 4, Day 7 and Day 14 ] [ Designated as safety issue: No ]
    Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 [ Time Frame: Day 2, Day 4, Day 7, Day 14 ] [ Designated as safety issue: No ]
    Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Y-MRS responders are defined as having a >= 50% decrease from baseline in Y-MRS total score.

  • Percentage of Participants Who Are Y-MRS Remitters at Day 21 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Y-MRS remitters are defined as having a Y-MRS total score of 12 or lower.

  • Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 [ Time Frame: Day 2, Day 4, Day 7, Day 14, Day 21 ] [ Designated as safety issue: No ]
    Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a generalized linear mixed model (GLMM). Y-MRS remitters are defined as having a Y-MRS total score of 12 or lower.

  • Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline and Day 7 and Day 21 ] [ Designated as safety issue: No ]
    The MADRS measures depression and consists of 10 items, each rated on a scale from 0 to 6. The MADRS total score sums the scores from the 10 items, ranging from 0 to 60, with a higher numeric rating implying a greater degree of symptom severity. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 [ Time Frame: Baseline and Day 2, Day 4, Day 7, Day 14 ] [ Designated as safety issue: No ]
    The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in CGI-BP-S Mania Score [ Time Frame: Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21 ] [ Designated as safety issue: No ]
    The CGI-BP-S mania is a score that assesses the severity of the mania component of bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in CGI-BP-S Depression Score [ Time Frame: Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21 ] [ Designated as safety issue: No ]
    The CGI-BP-S depression is a score that assesses the severity of the depression component of bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.

  • Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score [ Time Frame: Day 2, Day 4, Day 7, Day 14, and Day 21 ] [ Designated as safety issue: No ]
    The CGI-BP-I overall is a score on a 7-point scale for assessing the change from preceding phase of overall symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I overall score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.

  • Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score [ Time Frame: Day 2, Day 4, Day 7, Day 14, and Day 21 ] [ Designated as safety issue: No ]
    The CGI-BP-I mania is a score on a 7-point scale for assessing the change from preceding phase of mania symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I mania score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.

  • Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score [ Time Frame: Day 2, Day 4, Day 7, Day 14, and Day 21 ] [ Designated as safety issue: No ]
    The CGI-BP-I depression is a score on a 7-point scale for assessing the change from preceding phase of depression symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I depression score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.

  • Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score [ Time Frame: Baseline and Day 7, Day 14, Day 21 ] [ Designated as safety issue: No ]
    PANSS total score measures symptoms of schizophrenia and consists of responses to 30 items: 7 items from the positive subscale (P1-P7), 7 items from the negative subscale (N1-N7) and 16 items from the general psychopathology subscale (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS total score sums the scores from all 30 items, and ranges from 30 to 210, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in PANSS Negative Subscale Score [ Time Frame: Baseline and Day 7, Day 14, Day 21 ] [ Designated as safety issue: No ]
    PANSS Negative subscale measures symptoms of schizophrenia and consists of responses to 7 items (N1-N7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Negative subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in PANSS Positive Subscale Score [ Time Frame: Baseline and Day 7, Day 14, Day 21 ] [ Designated as safety issue: No ]
    PANSS Positive subscale measures symptoms of schizophrenia and consists of responses to 7 items (P1-P7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Positive subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in PANSS General Psychopathology Subscale Score [ Time Frame: Baseline and Day 7, Day 14, Day 21 ] [ Designated as safety issue: No ]
    PANSS General Psychopathology subscale measures symptoms of schizophrenia and consists of responses to 16 items (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS General Psychopathology subscale sums the scores from all 16 items and ranges from 16 to 112, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in PANSS Marder Factor Positive Symptom Score [ Time Frame: Baseline and Day 7, Day 14, Day 21 ] [ Designated as safety issue: No ]
    PANSS Marder Factor Positive symptom score measures symptoms of schizophrenia and consists of responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Positive symptom score sums the scores from all 8 items and ranges from 8 to 56, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in PANSS Marder Factor Negative Symptom Score [ Time Frame: Baseline and Day 7, Day 14, Day 21 ] [ Designated as safety issue: No ]
    PANSS Marder Factor Negative symptom score measures symptoms of schizophrenia and consists of responses to 7 items (N1,N2,N3,N4,N6,G7,G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Negative symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score [ Time Frame: Baseline and Day 7, Day 14, Day 21 ] [ Designated as safety issue: No ]
    PANSS Marder Factor Disorganized Thought symptom score measures symptoms of schizophrenia and consists of responses to 7 items (P2,N5,G5,G10,G11,G13,G15). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Disorganized Thought symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score [ Time Frame: Baseline and Day 7, Day 14, Day 21 ] [ Designated as safety issue: No ]
    PANSS Marder Factor Hostility/Excitement symptom score measures symptoms of schizophrenia and consists of responses to 4 items (P4,P7,G8,G14). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Hostility/Excitement symptom score sums the score from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

  • Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score [ Time Frame: Baseline and Day 7, Day14, Day 21 ] [ Designated as safety issue: No ]
    PANSS Marder Factor Anxiety/Depression symptom score measures symptoms of schizophrenia and consists of responses to 4 items (G2,G3,G4,G6). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Anxiety/Depression symptom score sums the scores from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.


Enrollment: 367
Study Start Date: April 2012
Study Completion Date: May 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Asenapine 5 mg BID
Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days
Drug: Asenapine
asenapine tablet, 5 mg sublingually BID for 21 days
Other Name: SCH 900274, Saphris®, Sycrest®, Org 5222
Experimental: Asenapine 10 mg BID
Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days
Drug: Asenapine
asenapine tablet, 10 mg sublingually BID for 21 days
Other Name: SCH 900274, Saphris®, Sycrest®, Org 5222
Placebo Comparator: Placebo BID
Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
Drug: Placebo
placebo sublingual tablet, administered BID for 21 days

  Eligibility

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

Inclusion Criteria:

  • Each participant must be at least 18 years of age
  • Male, or a female who is not of child-bearing potential or who is non-pregnant, non-lactating, and is using a medically accepted method of contraception
  • Each participant must have a current diagnosis of Bipolar I Disorder, current episode manic or mixed
  • Each participant must be confirmed to be experiencing an acute manic or mixed bipolar 1 episode
  • Each participant must have discontinued the use of all prohibited psychotropic medications

Exclusion Criteria:

  • A participant must not have a primary Axis I disorder other than Bipolar 1 Disorder (i.e., an Axis 1 disorder other than Bipolar 1 Disorder that is primarily responsible for current symptoms and functional impairment)
  • A participant must not currently (within the past 6 months) meet the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR™) criteria for substance abuse or dependence (excluding nicotine)
  • 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 (CSSRS).
  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: NCT00764478

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: NCT00764478     History of Changes
Other Study ID Numbers: P05691, 2010-018409-13, MK-8274-003
Study First Received: September 30, 2008
Results First Received: March 26, 2015
Last Updated: April 8, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
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 May 21, 2015