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

June 5, 2024 updated by: Organon and Co

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])

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
367

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

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: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • SCH 900274, Saphris®, Sycrest®, Org 5222
Drug: Asenapine
asenapine tablet, 10 mg sublingually BID for 21 days
Other Names:
  • 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, 5 mg sublingually BID for 21 days
Other Names:
  • SCH 900274, Saphris®, Sycrest®, Org 5222
Drug: Asenapine
asenapine tablet, 10 mg sublingually BID for 21 days
Other Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score at Day 21
Time Frame: Baseline and Day 21
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.
Baseline and Day 21

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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.
Baseline and Day 21
Percentage of Participants Who Are Y-MRS Responders at Day 21
Time Frame: Day 21
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.
Day 21
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
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.
Baseline and Day 2, Day 4, Day 7 and Day 14
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
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.
Day 2, Day 4, Day 7, Day 14
Percentage of Participants Who Are Y-MRS Remitters at Day 21
Time Frame: Day 21
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.
Day 21
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
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.
Day 2, Day 4, Day 7, Day 14, Day 21
Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score
Time Frame: Baseline and Day 7 and Day 21
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.
Baseline and Day 7 and Day 21
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
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.
Baseline and Day 2, Day 4, Day 7, Day 14
Change From Baseline in CGI-BP-S Mania Score
Time Frame: Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21
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.
Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21
Change From Baseline in CGI-BP-S Depression Score
Time Frame: Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21
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.
Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21
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
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.
Day 2, Day 4, Day 7, Day 14, and Day 21
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
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.
Day 2, Day 4, Day 7, Day 14, and Day 21
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
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.
Day 2, Day 4, Day 7, Day 14, and Day 21
Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score
Time Frame: Baseline and Day 7, Day 14, Day 21
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.
Baseline and Day 7, Day 14, Day 21
Change From Baseline in PANSS Negative Subscale Score
Time Frame: Baseline and Day 7, Day 14, Day 21
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.
Baseline and Day 7, Day 14, Day 21
Change From Baseline in PANSS Positive Subscale Score
Time Frame: Baseline and Day 7, Day 14, Day 21
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.
Baseline and Day 7, Day 14, Day 21
Change From Baseline in PANSS General Psychopathology Subscale Score
Time Frame: Baseline and Day 7, Day 14, Day 21
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.
Baseline and Day 7, Day 14, Day 21
Change From Baseline in PANSS Marder Factor Positive Symptom Score
Time Frame: Baseline and Day 7, Day 14, Day 21
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.
Baseline and Day 7, Day 14, Day 21
Change From Baseline in PANSS Marder Factor Negative Symptom Score
Time Frame: Baseline and Day 7, Day 14, Day 21
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.
Baseline and Day 7, Day 14, Day 21
Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score
Time Frame: Baseline and Day 7, Day 14, Day 21
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.
Baseline and Day 7, Day 14, Day 21
Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score
Time Frame: Baseline and Day 7, Day 14, Day 21
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.
Baseline and Day 7, Day 14, Day 21
Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score
Time Frame: Baseline and Day 7, Day14, Day 21
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.
Baseline and Day 7, Day14, Day 21

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Organon and Co

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Director, Merck Sharp & Dohme LLC

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.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 6, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 28, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 30, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 1, 2008

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 2, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 18, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P05691
  • 2010-018409-13 (EudraCT Number)
  • MK-8274-003 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

  1. CSR Synopsis

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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