40 Week Extension Study Of Asenapine and Olanzapine For Bipolar Disorder (A7501007)(COMPLETED)(P05857)

Sponsor
Organon and Co (Industry)
Overall Status
Completed
CT.gov ID
NCT00159783
Collaborator
Pfizer (Industry)
218
2
21

Study Details

Study Description

Brief Summary

Bipolar disorder is characterized by mood swings that range from from high (manic) to low (depressed) states. Sometimes, symptoms of both depression and mania are present (mixed episodes). Asenapine is an investigational medication for the treatment of manic or mixed episodes of bipolar disorder. Patients who completed study A7501006 (a 9 week extension study) could continue with the same treatment that they had been receiving: asenapine or olanzapine (a medication that is already approved for the treatment of bipolar mania) in a 40 -week continuation study.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
218 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Double-Blind, 40-Week Continuation Study Evaluating the Safety of Asenapine and Olanzapine in the Treatment of Subjects With Acute Mania Clinical Trial Protocol A7501007 (Secondary Title: ARES)
Study Start Date :
Jul 1, 2005
Actual Primary Completion Date :
Apr 1, 2007
Actual Study Completion Date :
Apr 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Experimental: Asenapine

Asenapine 5-10 mg twice daily for 40 weeks

Drug: asenapine
Asenapine, 40 weeks
Other Names:
  • Org 5222
  • Active Comparator: Olanzapine

    Olanzapine 5-20 mg once daily for 40 weeks

    Drug: Olanzapine
    Olanzapine, 40 weeks

    Outcome Measures

    Primary Outcome Measures

    1. Participants Who Experienced Adverse Event(s) [Up to 40 weeks]

      Adverse event (AE) data, both serious and non-serious, were collected. Serious AEs were also collected up to 30 days post last dose of study drug. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product. It does not necessarily have to have a causal relationship with this treatment. An AE is defined as serious if it results in death, is life-threatening, requires in-patient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

    2. Number of Participants With Abnormal Physical Examination Findings [Week 40 or endpoint]

      Physical exam (PE) included assessment of general appearance, skin, head, eyes, ears, nose, throat, lungs, blood pressure, cardiac rhythm & rate, neurologic status, and abdomen. The findings were deemed to be normal/abnormal based on the clinical judgment of the investigator.

    3. Number of Participants With Abnormal Electrocardiogram [Week 40 or endpoint]

      This is the number of participants with electrocardiogram (ECG) adverse events.

    4. Body Weight [Baseline to Week 40 or endpoint]

      Weight change from baseline

    5. Extrapyramidal Symptoms [EPS] [Week 40 or endpoint]

      EPS was assessed using the (1) involuntary movement scale [AIMS], (2) Barnes Akathisia Rating Scale [BARS], and (3) Simpson Angus Rating Scale SARS. AIMS score range 0-4; higher scores indicate greater symptom severity. BARS score rang 0-9; higher scores indicate greater severity of akathisia. SARS score range 0-40; higher scores indicate greater degree of Parkinsonism.

    6. Concomitant Medications [Up to 40 weeks]

      Concomitant medications are any medications taken on or after the date of first dose of double-blind study drug through the date of last dose of double-blind study drug.

    7. Abdominal Girth [Baseline to Week 40 or endpoint]

      Change in abdominal girth from baseline

    8. Number of Participants With Markedly Abnormal Vital Sign Changes [Post-baseline (at Week 4, 12, 20, 28, and 40 or endpoint)]

      Vital signs measured: sitting blood pressure, heart rate. Definitions: Markedly abnormal decreases: heart rate (HR) - if ≤50 bpm and decrease from baseline of ≥15 beats per minute (bpm); systolic blood pressure (SBP) - if ≤90 mm Hg and decrease from baseline of ≥20 mm Hg; diastolic blood pressure (DBP) - if ≤50 mm Hg and decrease from baseline of ≥15 mm Hg. Markedly abnormal increases: HR - if ≥110 bpm and increase from baseline of ≥15 bpm; SBP - if ≥180 mm Hg and increase from baseline of ≥20 mm Hg; DBP - if ≥105 mm Hg and increase from baseline of ≥15 mm Hg.

    9. Number of Participants With Laboratory Values Outside Normal Range [Week 40 or endpoint]

      Normal ranges were provided by the central laboratory. Biochemistry = electrolytes, creatine kinase, liver enzymes, blood urea nitrogen, creatinine, alkaline phosphatase, protein, albumin Metabolic chemistry = cholesterol, glucose, triglycerides, glycosylated hemoglobin Endocrinology/miscellaneous = insulin, prolactin Hematology = hemoglobin, red blood cell count, white blood cell count, platelets, hematocrit, neutrophils, lymphocytes, monocytes, eosinophils, basophils

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Have completed asenapine 3-week and 9 -week studies for the treatment of an acute manic or mixed episode and not had any major protocol violations..
    Exclusion Criteria:
    • Patients with unstable medical conditions or clinically significant laboratory

    abnormalities.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Organon and Co
    • Pfizer

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Organon and Co
    ClinicalTrials.gov Identifier:
    NCT00159783
    Other Study ID Numbers:
    • P05857
    • A7501007
    First Posted:
    Sep 12, 2005
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
    Period Title: Overall Study
    STARTED 32 79 107
    COMPLETED 13 52 68
    NOT COMPLETED 19 27 39

    Baseline Characteristics

    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine Total
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks Total of all reporting groups
    Overall Participants 32 79 107 218
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    31
    96.9%
    77
    97.5%
    106
    99.1%
    214
    98.2%
    >=65 years
    1
    3.1%
    2
    2.5%
    1
    0.9%
    4
    1.8%
    Sex: Female, Male (Count of Participants)
    Female
    15
    46.9%
    43
    54.4%
    39
    36.4%
    97
    44.5%
    Male
    17
    53.1%
    36
    45.6%
    68
    63.6%
    121
    55.5%

    Outcome Measures

    1. Primary Outcome
    Title Participants Who Experienced Adverse Event(s)
    Description Adverse event (AE) data, both serious and non-serious, were collected. Serious AEs were also collected up to 30 days post last dose of study drug. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product. It does not necessarily have to have a causal relationship with this treatment. An AE is defined as serious if it results in death, is life-threatening, requires in-patient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
    Time Frame Up to 40 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
    Measure Participants 32 79 107
    Number [Participants]
    23
    71.9%
    68
    86.1%
    85
    79.4%
    2. Primary Outcome
    Title Number of Participants With Abnormal Physical Examination Findings
    Description Physical exam (PE) included assessment of general appearance, skin, head, eyes, ears, nose, throat, lungs, blood pressure, cardiac rhythm & rate, neurologic status, and abdomen. The findings were deemed to be normal/abnormal based on the clinical judgment of the investigator.
    Time Frame Week 40 or endpoint

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title All Treatment Groups
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks or Olanzapine 5-20 mg daily for 40 weeks
    Measure Participants 218
    Number [Participants]
    32
    100%
    3. Primary Outcome
    Title Number of Participants With Abnormal Electrocardiogram
    Description This is the number of participants with electrocardiogram (ECG) adverse events.
    Time Frame Week 40 or endpoint

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
    Measure Participants 32 79 107
    Sinus bradycardia
    0
    0%
    2
    2.5%
    0
    0%
    Bundle branch block right
    0
    0%
    1
    1.3%
    0
    0%
    ECG QRS complex prolonged
    0
    0%
    0
    0%
    1
    0.9%
    ECG ST segment depression
    0
    0%
    0
    0%
    1
    0.9%
    ECG T wave inversion
    0
    0%
    0
    0%
    1
    0.9%
    Supraventricular extrasystoles
    0
    0%
    0
    0%
    1
    0.9%
    Ventricular extrasystoles
    0
    0%
    0
    0%
    1
    0.9%
    4. Primary Outcome
    Title Body Weight
    Description Weight change from baseline
    Time Frame Baseline to Week 40 or endpoint

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
    Measure Participants 32 79 107
    Baseline
    81.4
    (19.94)
    68.1
    (17.22)
    72.0
    (19.96)
    Change from baseline to Week 40 or endpoint
    1.7
    (5.95)
    3.5
    (6.65)
    6.0
    (6.59)
    5. Primary Outcome
    Title Extrapyramidal Symptoms [EPS]
    Description EPS was assessed using the (1) involuntary movement scale [AIMS], (2) Barnes Akathisia Rating Scale [BARS], and (3) Simpson Angus Rating Scale SARS. AIMS score range 0-4; higher scores indicate greater symptom severity. BARS score rang 0-9; higher scores indicate greater severity of akathisia. SARS score range 0-40; higher scores indicate greater degree of Parkinsonism.
    Time Frame Week 40 or endpoint

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
    Measure Participants 32 79 107
    AIMS
    0.4
    (1.37)
    0.1
    (0.60)
    0.0
    (0.14)
    BARS
    0.4
    (1.21)
    0.2
    (0.77)
    0.1
    (0.55)
    SARS
    0.6
    (1.72)
    0.2
    (1.36)
    0.3
    (1.15)
    6. Primary Outcome
    Title Concomitant Medications
    Description Concomitant medications are any medications taken on or after the date of first dose of double-blind study drug through the date of last dose of double-blind study drug.
    Time Frame Up to 40 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
    Measure Participants 32 79 107
    Participants with no concomitant medications
    10
    31.3%
    21
    26.6%
    31
    29%
    Participants with >=1 concomitant medication
    22
    68.8%
    58
    73.4%
    76
    71%
    7. Primary Outcome
    Title Abdominal Girth
    Description Change in abdominal girth from baseline
    Time Frame Baseline to Week 40 or endpoint

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
    Measure Participants 32 79 107
    Baseline
    91.1
    (14.20)
    86.8
    (14.79)
    89.4
    (14.78)
    Change from baseline to Week 40 or endpoint
    3.0
    (6.84)
    2.6
    (6.87)
    5.0
    (7.89)
    8. Primary Outcome
    Title Number of Participants With Markedly Abnormal Vital Sign Changes
    Description Vital signs measured: sitting blood pressure, heart rate. Definitions: Markedly abnormal decreases: heart rate (HR) - if ≤50 bpm and decrease from baseline of ≥15 beats per minute (bpm); systolic blood pressure (SBP) - if ≤90 mm Hg and decrease from baseline of ≥20 mm Hg; diastolic blood pressure (DBP) - if ≤50 mm Hg and decrease from baseline of ≥15 mm Hg. Markedly abnormal increases: HR - if ≥110 bpm and increase from baseline of ≥15 bpm; SBP - if ≥180 mm Hg and increase from baseline of ≥20 mm Hg; DBP - if ≥105 mm Hg and increase from baseline of ≥15 mm Hg.
    Time Frame Post-baseline (at Week 4, 12, 20, 28, and 40 or endpoint)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
    Measure Participants 32 79 107
    Number [Participants]
    2
    6.3%
    12
    15.2%
    11
    10.3%
    9. Primary Outcome
    Title Number of Participants With Laboratory Values Outside Normal Range
    Description Normal ranges were provided by the central laboratory. Biochemistry = electrolytes, creatine kinase, liver enzymes, blood urea nitrogen, creatinine, alkaline phosphatase, protein, albumin Metabolic chemistry = cholesterol, glucose, triglycerides, glycosylated hemoglobin Endocrinology/miscellaneous = insulin, prolactin Hematology = hemoglobin, red blood cell count, white blood cell count, platelets, hematocrit, neutrophils, lymphocytes, monocytes, eosinophils, basophils
    Time Frame Week 40 or endpoint

    Outcome Measure Data

    Analysis Population Description
    Number at risk = participants with either normal or abnormal baseline value and a non-missing value at endpoint. Actual at risk: 20-32 for placebo/asenapine arm; 50-78 for asenapine arm; 63-106 in olanzapine arm.
    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
    Measure Participants 32 79 107
    Biochemistry
    25
    78.1%
    76
    96.2%
    115
    107.5%
    Metabolic chemistry
    17
    53.1%
    32
    40.5%
    96
    89.7%
    Endocrinology/miscellaneous
    7
    21.9%
    35
    44.3%
    39
    36.4%
    Hematology
    22
    68.8%
    90
    113.9%
    83
    77.6%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
    Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
    All Cause Mortality
    Placebo/Asenapine Asenapine Olanzapine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo/Asenapine Asenapine Olanzapine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/32 (6.3%) 6/79 (7.6%) 9/107 (8.4%)
    Cardiac disorders
    Cardiac failure 0/32 (0%) 0 0/79 (0%) 0 1/107 (0.9%) 1
    General disorders
    Death neonatal 0/32 (0%) 0 1/79 (1.3%) 1 0/107 (0%) 0
    Injury, poisoning and procedural complications
    Drug exposure during pregnancy 0/32 (0%) 0 1/79 (1.3%) 1 0/107 (0%) 0
    Psychiatric disorders
    Bipolar I disorder 0/32 (0%) 0 1/79 (1.3%) 1 2/107 (1.9%) 2
    Completed suicide 0/32 (0%) 0 0/79 (0%) 0 1/107 (0.9%) 1
    Depression 2/32 (6.3%) 2 3/79 (3.8%) 3 3/107 (2.8%) 3
    Mania 0/32 (0%) 0 0/79 (0%) 0 2/107 (1.9%) 2
    Psychotic disorder 0/32 (0%) 0 1/79 (1.3%) 1 0/107 (0%) 0
    Suicidal ideation 1/32 (3.1%) 1 0/79 (0%) 0 0/107 (0%) 0
    Suicide attempt 0/32 (0%) 0 0/79 (0%) 0 1/107 (0.9%) 1
    Other (Not Including Serious) Adverse Events
    Placebo/Asenapine Asenapine Olanzapine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/32 (37.5%) 28/79 (35.4%) 34/107 (31.8%)
    Gastrointestinal disorders
    Dyspepsia 2/32 (6.3%) 2 1/79 (1.3%) 1 0/107 (0%) 0
    General disorders
    Fatigue 1/32 (3.1%) 1 1/79 (1.3%) 1 7/107 (6.5%) 7
    Pyrexia 0/32 (0%) 0 2/79 (2.5%) 3 6/107 (5.6%) 6
    Infections and infestations
    Nasopharyngitis 2/32 (6.3%) 2 1/79 (1.3%) 1 4/107 (3.7%) 6
    Investigations
    Weight decreased 3/32 (9.4%) 3 4/79 (5.1%) 4 0/107 (0%) 0
    Weight increased 1/32 (3.1%) 2 5/79 (6.3%) 5 8/107 (7.5%) 8
    Musculoskeletal and connective tissue disorders
    Back pain 2/32 (6.3%) 2 2/79 (2.5%) 2 1/107 (0.9%) 1
    Nervous system disorders
    Parkinsonism 2/32 (6.3%) 2 2/79 (2.5%) 2 1/107 (0.9%) 4
    Sedation 1/32 (3.1%) 1 5/79 (6.3%) 5 5/107 (4.7%) 7
    Somnolence 2/32 (6.3%) 2 3/79 (3.8%) 3 3/107 (2.8%) 3
    Insomnia 2/32 (6.3%) 5 6/79 (7.6%) 7 7/107 (6.5%) 14
    Psychiatric disorders
    Depression 2/32 (6.3%) 2 7/79 (8.9%) 8 5/107 (4.7%) 5

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    If study is part of a multicenter trial, Investigator agrees that the first publication is to be a joint publication covering all centers. However, if a joint manuscript has not been submitted for publication within 12 mos of completion or termination of study at all participating sites, Investigator is free to publish separately. The sponsor should review any publication prior to submission for publication to ensure no confidential information is released inadvertently.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Organon and Co
    ClinicalTrials.gov Identifier:
    NCT00159783
    Other Study ID Numbers:
    • P05857
    • A7501007
    First Posted:
    Sep 12, 2005
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022