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    Clinical Trial Results:
    A Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dosage Study to Evaluate the Efficacy and Safety of Armodafinil Treatment (150 mg/day) as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

    Summary
    EudraCT number
    2010-023623-26
    Trial protocol
    HU   FI   DE   IT   PL   BG  
    Global end of trial date
    29 Jul 2013

    Results information
    Results version number
    v2(current)
    This version publication date
    17 Jul 2016
    First version publication date
    21 May 2015
    Other versions
    v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    QC check completed, data are correct

    Trial information

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    Trial identification
    Sponsor protocol code
    C10953/3073
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01305408
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Teva Branded Pharmaceutical Products R&D, Inc.
    Sponsor organisation address
    41 Moores Road, Frazer, Pennsylvania, United States, 19355-1113
    Public contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products R&D, Inc., 1 215-591-3000, ustevatrials@tevapharm.com
    Scientific contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products R&D, Inc., 1 215-591-3000, ustevatrials@tevapharm.com
    Sponsor organisation name
    Teva Branded Pharmaceutical Products, R&D Inc.
    Sponsor organisation address
    41 Moores Road, Fraser, PA, United States, 19355-1113
    Public contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products R&D, Inc., +1 215-591-3000, ustevatrials@tevapharm.com
    Scientific contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products R&D, Inc., +1 215-591-3000, ustevatrials@tevapharm.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Jul 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jul 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to determine whether armodafinil treatment, at a dosage of 150 mg/day, is more effective than placebo treatment as adjunctive therapy to mood stabilizers for treatment of adults with major depression associated with bipolar I disorder. Efficacy will be assessed by the mean change from baseline in the total score from the 30-Item Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30).
    Protection of trial subjects
    This study was conducted in full accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations (eg, Title 21 Code of Federal Regulations [21CFR] Parts 11, 50, 54, 56, 312, and 314, European Union [EU] Directive 2001/20/EC, and 2005/28/EC. Each investigator was responsible for performing the study in accordance with the protocol, ICH guidelines, and GCP, and for collecting, recording, and reporting the data accurately and properly. Agreement of each investigator to conduct and administer this study in accordance with the protocol was documented in separate study agreements with the sponsor and other forms as required by national authorities in the country where the investigational center is located. Written and/or oral information about the study was provided to all patients in a language understandable by the patients. The information included an adequate explanation of the aims, methods, anticipated benefits, potential hazards, and insurance arrangements in force. Written informed consent was obtained from each patient before any study procedures or assessments were done. It was explained to the patients that they were free to refuse entry into the study and free to withdraw from the study at any time without prejudice to future treatment. Each patient’s willingness to participate in the study was documented in writing in a consent form that was signed by the patient with the date of that signature indicated. Each investigator kept the original consent forms, and copies were given to the patients.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    17 Feb 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    6 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 35
    Country: Number of subjects enrolled
    Bulgaria: 53
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Hungary: 25
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Argentina: 14
    Country: Number of subjects enrolled
    Brazil: 18
    Country: Number of subjects enrolled
    Croatia: 13
    Country: Number of subjects enrolled
    Serbia: 12
    Country: Number of subjects enrolled
    Slovakia: 13
    Country: Number of subjects enrolled
    Ukraine: 56
    Country: Number of subjects enrolled
    United States: 123
    Country: Number of subjects enrolled
    South Africa: 27
    Worldwide total number of subjects
    399
    EEA total number of subjects
    149
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    396
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Region 1: USA and Canada Region 2: Eastern European countries, Kyrgyzstan, Mongolia, Uzbekistan, Cyprus, Greece, and Turkey Region 3: Central and Northern European countries, Andorra, Australia, Iceland, Monaco, San Marino, and Vatican City Region 4: Rest of World

    Pre-assignment
    Screening details
    Participants were randomized (1:1) to receive150 mg/day armodafinil or matching placebo. Randomization was stratified on the basis of the mood-stabilizing medication and region of the world.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo tablets, taken orally, once daily in the morning

    Arm title
    Armodafinil 150 mg/day
    Arm description
    Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. Treatment was administered for a total of 8 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Armodafinil
    Investigational medicinal product code
    Other name
    Nuvigil, CEP-10953
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Armodafinil tablets, taken orally, once daily in the morning

    Number of subjects in period 1
    Placebo Armodafinil 150 mg/day
    Started
    199
    200
    Safety Population
    198
    200
    Full Analysis Population
    196
    197
    Completed
    167
    169
    Not completed
    32
    31
         Protocol deviation
    4
    6
         Noncompliance with sutdy procedures
    -
    1
         Noncompliance with study medication
    -
    1
         Lack of efficacy
    3
    4
         Adverse event, non-fatal
    10
    7
         Extended absence
    1
    -
         Consent withdrawn by subject
    9
    9
         Lost to follow-up
    5
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.

    Reporting group title
    Armodafinil 150 mg/day
    Reporting group description
    Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. Treatment was administered for a total of 8 weeks.

    Reporting group values
    Placebo Armodafinil 150 mg/day Total
    Number of subjects
    199 200 399
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    43.7 ± 11.62 45.3 ± 11.26 -
    Gender categorical
    Units: Subjects
        Female
    121 120 241
        Male
    78 80 158
    Race
    Units: Subjects
        White
    176 182 358
        Black
    16 14 30
        Asian
    1 2 3
        American Indian or Alaskan Native
    0 2 2
        Other
    6 0 6
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    14 22 36
        Non-Hispanic or non-Latino
    183 176 359
        Unknown
    2 2 4
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    81.2 ± 17.46 80.7 ± 17.54 -
    Height
    Units: cm
        arithmetic mean (standard deviation)
    168.4 ± 9.32 168.9 ± 9.23 -
    Body Mass Index
    Units: kg/m^2
        arithmetic mean (standard deviation)
    28.7 ± 5.95 28.2 ± 5.52 -
    Time since start of current depressive episode
    Units: weeks
        arithmetic mean (standard deviation)
    12.1 ± 9.1 12.3 ± 9.89 -
    Time since first diagnosis
    Units: years
        arithmetic mean (standard deviation)
    9.9 ± 8.72 10.7 ± 8.55 -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.

    Reporting group title
    Armodafinil 150 mg/day
    Reporting group description
    Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. Treatment was administered for a total of 8 weeks.

    Primary: Change From Baseline to Week 8 in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)

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    End point title
    Change From Baseline to Week 8 in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)
    End point description
    The IDS-C30 is a standardized 30-item, clinician-rated scale to assess the severity of a participant's depressive symptoms. Every effort was made to have the same rater evaluate a participant across all visits. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Negative change from baseline values indicate improvement in the severity of depression.
    End point type
    Primary
    End point timeframe
    Day 0 (baseline), Week 8
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    196 [1]
    197 [2]
    Units: units on a scale
        least squares mean (standard error)
    -19.4 ± 0.99
    -20.8 ± 0.99
    Notes
    [1] - Full analysis set -participants with 1+ doses of study drug and 1+ postbaseline IDS-C30 assessment
    [2] - Full analysis set -participants with 1+ doses of study drug and 1+ postbaseline IDS-C30 assessment
    Statistical analysis title
    Total Score for the IDS-C30
    Statistical analysis description
    Treatment, visit, treatment-by-visit interaction, concurrent mood-stabilizing medication, and region of the world used as fixed factors.
    Comparison groups
    Placebo v Armodafinil 150 mg/day
    Number of subjects included in analysis
    393
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2717 [3]
    Method
    Mixed-model repeated measures (MMRM)
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.76
         upper limit
    1.06
    Notes
    [3] - Statistical tests were 2-tailed at the 0.05 level of significance.

    Secondary: Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score

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    End point title
    Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score
    End point description
    A responder is a participant with a ≥50% decrease or greater from baseline in the total score of the IDS-C30. The IDS-C30 is a standardized 30-item, clinician-rated scale to assess the severity of a participant's depressive symptoms. Every effort was made to have the same rater evaluate a participant across all visits. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 post-baseline IDS-C30 efficacy assessment. The denominator for calculating the percentages at each visit is the number of participants with a non-missing value at that visit. Endpoint was the last observed post-baseline data.
    End point type
    Secondary
    End point timeframe
    Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    196 [4]
    197 [5]
    Units: percentage of participants
    number (not applicable)
        Week 1 (n=196, 195)
    2
    3
        Week 2 (n=187, 189)
    13
    9
        Week 4 (n=181, 183)
    21
    27
        Week 6 (n=172, 172)
    29
    41
        Week 7 (n=167, 170)
    39
    51
        Week 8 (n=167, 169)
    46
    56
        Endpoint (n=196, 197)
    41
    49
    Notes
    [4] - Full analysis set
    [5] - Full analysis set
    No statistical analyses for this end point

    Secondary: Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score

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    End point title
    Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score
    End point description
    A participant in remission was defined as a participant with an IDS-C30 total score of 11 or less. The IDS-C30 is a standardized 30-item, clinician-rated scale to assess the severity of a participant's depressive symptoms. Every effort was made to have the same rater evaluate a participant across all visits. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 post-baseline IDS-C30 efficacy assessment. The denominator for calculating the percentages at each visit is the number of participants with a non-missing value at that visit. Endpoint was the last observed post-baseline data.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    196 [6]
    197 [7]
    Units: percentage of participants
    number (not applicable)
        Week 1 (n=196, 195)
    0.5
    1
        Week 2 (n=187, 189)
    2
    2
        Week 4 (n=181, 183)
    5
    7
        Week 6 (n=172, 172)
    9
    12
        Week 7 (n=167, 170)
    14
    19
        Week 8 (n=167, 169)
    15
    26
        Endpoint (196, 197)
    13
    22
    Notes
    [6] - Full analysis set
    [7] - Full analysis set
    No statistical analyses for this end point

    Secondary: Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)

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    End point title
    Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)
    End point description
    The IDS-C30 is a standardized 30-item, clinician-rated scale to assess the severity of a participant's depressive symptoms. Every effort was made to have the same rater evaluate a participant across all visits. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Negative change from baseline values indicate improvement in the severity of depression. Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 post-baseline IDS-C30 efficacy assessment. Participants are included in the analysis at each timepoint if they have a non-missing value at that visit. Endpoint for analyses was the last observed post-baseline data.
    End point type
    Secondary
    End point timeframe
    Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    196 [8]
    197 [9]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 1 (n=196, 195)
    -6 ± 6.61
    -5.3 ± 7.12
        Week 2 (n=187, 189)
    -10 ± 8.71
    -8.9 ± 8.56
        Week 4 (n=181, 183)
    -13.4 ± 9.87
    -13.5 ± 10.54
        Week 6 (n=172, 172)
    -15.8 ± 10.42
    -17.6 ± 11.09
        Week 7 (n=167, 170)
    -18 ± 11.42
    -20.2 ± 10.88
        Week 8 (n=167, 169)
    -19.7 ± 11.3
    -21.6 ± 11.75
        Endpoint (n=196, 197)
    -18.3 ± 11.62
    -19.5 ± 12.66
    Notes
    [8] - Full analysis set
    [9] - Full analysis set
    No statistical analyses for this end point

    Secondary: Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16)

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    End point title
    Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16)
    End point description
    The QIDS-C16 was derived from specified items in the IDS-C30, clinician-rated scale to assess the severity of a participant's depressive symptoms. Total scores range from 0-27, with a score of 0 indicating no depression and a score of 27 indicating the most severe depression. Negative change from baseline values indicate improvement in the severity of depression. Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 post-baseline IDS-C30 efficacy assessment. The number of participants at each visit are those with a non-missing value at that visit. Endpoint was the last observed post-baseline data.
    End point type
    Secondary
    End point timeframe
    Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    196 [10]
    197 [11]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 1 (n=196, 195)
    -2.4 ± 2.92
    -2.1 ± 3.07
        Week 2 (n=187, 189)
    -4.2 ± 3.83
    -3.4 ± 3.63
        Week 4 (n=181, 183)
    -5.3 ± 4.05
    -5.3 ± 4.15
        Week 6 (n=172, 172)
    -6.3 ± 4.16
    -6.7 ± 4.38
        Week 7 (n=167, 170)
    -7.2 ± 4.49
    -7.8 ± 4.35
        Week 8 (n=167, 169)
    -8 ± 4.53
    -8.3 ± 4.62
        Endpoint (n=196, 197)
    -7.3 ± 4.73
    -7.5 ± 4.91
    Notes
    [10] - Full analysis set
    [11] - Full analysis set
    No statistical analyses for this end point

    Secondary: Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression

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    End point title
    Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression
    End point description
    The CGI-S is an observer-rated scale that measures illness severity on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). Negative change from baseline values indicate improvement in the severity of depression. Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 post-baseline IDS-C30 efficacy assessment. The number of participants is those with a non-missing value at that visit. Endpoint was the last observed post-baseline data.
    End point type
    Secondary
    End point timeframe
    Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    196 [12]
    197 [13]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 1 (n=196, 195)
    -0.2 ± 0.49
    -0.2 ± 0.46
        Week 2 (n=187, 189)
    -0.5 ± 0.65
    -0.5 ± 0.77
        Week 4 (n=181, 183)
    -0.7 ± 0.76
    -0.9 ± 0.97
        Week 6 (n=172, 172)
    -1 ± 0.91
    -1.2 ± 1.03
        Week 7 (n=167, 170)
    -1.2 ± 1.08
    -1.4 ± 1.1
        Week 8 (n=167, 169)
    -1.3 ± 1.11
    -1.6 ± 1.19
        Endpoint (n=196, 197)
    -1.2 ± 1.14
    -1.4 ± 1.25
    Notes
    [12] - Full analysis set
    [13] - Full analysis set
    No statistical analyses for this end point

    Secondary: Change From Baseline to Weeks 4, 8 and Endpoint in the Global Assessment for Functioning (GAF) Scale

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    End point title
    Change From Baseline to Weeks 4, 8 and Endpoint in the Global Assessment for Functioning (GAF) Scale
    End point description
    The Global Assessment of Functioning (GAF) is a numeric scale (1 through 100) used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of adults, e.g., how well or adaptively one is meeting various problems-in-living. Ratings of 1 - 10 mean the participant is in persistent danger of severely hurting self or others (e.g., recurrent violence) or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death. Ratings of 91 - 100 indicate no symptoms, and the participant exhibits superior functioning in a wide range of activities, life's problems never seem to get out of hand, is sought out by others because of his or her many positive qualities. Positive change from baseline values indicate improvement in functioning. Full analysis set which includes participants who took 1+ doses of study drug and 1+ post-baseline IDS-C30 efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Day 0 (baseline), Weeks 4, 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    196 [14]
    197 [15]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 4 (n=181, 183)
    5.8 ± 7.39
    8.2 ± 10.39
        Week 8 (n=167, 169)
    11.5 ± 10.42
    15.3 ± 11.72
        Endpoint (n=189, 192)
    10.6 ± 10.42
    13.6 ± 12.38
    Notes
    [14] - Full analysis set
    [15] - Full analysis set
    No statistical analyses for this end point

    Secondary: Participants With Treatment-Emergent Adverse Events (TEAE)

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    End point title
    Participants With Treatment-Emergent Adverse Events (TEAE)
    End point description
    AEs were graded by the investigator for severity on a three-point scale: mild, moderate and severe. Causality is graded as either related or not related. A serious adverse event (SAE) is an AE resulting in death, a life-threatening adverse event, hospitalization, a persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may require medical intervention to prevent any of the previous results. Protocol-defined adverse events requiring expedited reporting included skin rash, hypersensitivity reaction, emergent suicidal ideation or suicide attempt, and psychosis.
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 9
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [16]
    200 [17]
    Units: participants
        >=1 adverse event
    71
    89
        Severe adverse event
    4
    4
        Treatment-related adverse event
    32
    53
        Deaths
    0
    0
        Other serious adverse events
    6
    5
        Withdrawn from study due to adverse events
    10
    7
        Protocol-defined adverse events
    3
    3
    Notes
    [16] - The safety analysis set includes randomized participants who took 1 or more doses of study drug.
    [17] - The safety analysis set includes randomized participants who took 1 or more doses of study drug.
    No statistical analyses for this end point

    Secondary: Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score

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    End point title
    Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score
    End point description
    The YMRS is a clinician-rated, 11-item checklist used to measure the severity of manic episodes. Information for assigning scores is gained from the participant's subjective reported symptoms over the previous 48 hours and from clinical observation during the interview. Seven items are ranked 0 through 4 and have descriptors associated with each severity level. Four items (irritability, speech, content, and disruptive-aggressive behavior) are scored 0 through 8 and have descriptors for every second increment. The total scale is 0-60. A score of ≤12 indicates remission of manic symptoms, and higher scores indicate greater severity of mania. Negative change from baseline scores indicate a decrease in severity of mania. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with both baseline and during treatment assessments.
    End point type
    Secondary
    End point timeframe
    Day 0 (baseline), last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    196 [18]
    198 [19]
    Units: units on a scale
        arithmetic mean (standard deviation)
    -1 ± 2.45
    -0.9 ± 3.19
    Notes
    [18] - Safety analysis set
    [19] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score

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    End point title
    Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score
    End point description
    HAM-A measures the severity of anxiety symptoms. The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Negative change from baseline scores indicate a decrease in severity of anxiety. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with both baseline and during treatment assessments.
    End point type
    Secondary
    End point timeframe
    Day 0 (baseline), last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    190 [20]
    194 [21]
    Units: units on a scale
        arithmetic mean (standard deviation)
    -4.2 ± 4.53
    -4.3 ± 5.37
    Notes
    [20] - Safety analysis set
    [21] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score

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    End point title
    Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score
    End point description
    The ISI is a participant-rated, 7-item questionnaire designed to assess the severity of the participant's insomnia. Each item is ranked 0 (none) through 4 (very severe) and has a descriptor associated with each severity level. Total range is 0 (no insomnia) to 28 (very severe insomnia). Responses to each item are added to obtain a total score to determine the severity of insomnia. Negative change from baseline scores indicate a decrease in severity of insomnia. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with both baseline and during treatment assessments.
    End point type
    Secondary
    End point timeframe
    Day 0 (baseline), last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    190 [22]
    192 [23]
    Units: units on a scale
        arithmetic mean (standard deviation)
    -7 ± 6.62
    -7.1 ± 6.91
    Notes
    [22] - Safety analysis set
    [23] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Actual Attempt Question

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    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Actual Attempt Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Actual Attempt question records whether the participant committed a potentially self-injurious act with at least some wish to die since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [24]
    200 [25]
    Units: participants
        Week 1 (n=196, 195)
    0
    0
        Week 2 (n=187, 189)
    0
    0
        Week 4 (n=181, 183)
    0
    0
        Week 6 (n=172, 172)
    0
    0
        Week 7 (n=167, 170)
    0
    0
        Week 8 (n=167, 169)
    0
    0
        Endpoint (n=196, 198)
    0
    0
    Notes
    [24] - Safety analysis set
    [25] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Non-Suicidal Self-Injurious Behavior Question

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    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Non-Suicidal Self-Injurious Behavior Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Non-Suicidal Self-Injurious Behavior question records whether the participant committed a potentially self-injurious act that was not associated with a wish to die since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [26]
    200 [27]
    Units: participants
        Week 1 (n=196, 195)
    0
    0
        Week 2 (n=187, 189)
    0
    0
        Week 4 (n=181, 183)
    0
    0
        Week 6 (n=172, 172)
    0
    0
        Week 7 (n=167, 170)
    0
    0
        Week 8 (n=167, 169)
    0
    0
        Endpoint (n=196, 198)
    0
    0
    Notes
    [26] - Safety analysis set
    [27] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Interrupted Attempt Question

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    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Interrupted Attempt Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Interrupted Attempt question records whether the participant was interrupted by an outside circumstance from starting the potentially self-injurious act with at least some wish to die since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [28]
    200 [29]
    Units: participants
        Week 1 (n=196, 195)
    0
    0
        Week 2 (n=187, 189)
    0
    0
        Week 4 (n=181, 183)
    0
    0
        Week 6 (n=172, 172)
    0
    0
        Week 7 (n=167, 170)
    0
    0
        Week 8 (n=167, 169)
    0
    0
        Endpoint (n=196, 198)
    0
    0
    Notes
    [28] - Safety analysis set
    [29] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Aborted Attempt Question

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    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Aborted Attempt Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Aborted Attempt question records whether the participant began to take steps toward making a suicide attempt but stops themselves before starting the potentially self-injurious act since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [30]
    200 [31]
    Units: participant
        Week 1 (n=196, 195)
    0
    0
        Week 2 (n=187, 189)
    0
    0
        Week 4 (n=181, 183)
    0
    0
        Week 6 (n=172, 172)
    0
    0
        Week 7 (n=167, 170)
    0
    0
        Week 8 (n=167, 169)
    0
    0
        Endpoint (n=196, 198)
    0
    0
    Notes
    [30] - Safety analysis set
    [31] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Suicidal Behavior Question

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    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Suicidal Behavior Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Suicidal Behavior question records whether in the clinician's opinion, the participant exhibited suicidal behavior since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [32]
    200 [33]
    Units: participants
        Week 1 (n=196, 195)
    0
    0
        Week 2 (n=187, 189)
    0
    0
        Week 4 (n=181, 183)
    0
    0
        Week 6 (n=172, 172)
    0
    0
        Week 7 (n=167, 170)
    0
    0
        Week 8 (n=167, 169)
    0
    0
        Endpoint (n=196, 198)
    0
    0
    Notes
    [32] - Safety analysis set
    [33] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Preparatory Acts or Behavior Question

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    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Preparatory Acts or Behavior Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Preparatory Acts or Behavior question records whether the participant exhibited acts or preparations towards imminently making a suicide attempt since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [34]
    200 [35]
    Units: participants
        Week 1 (n=196, 195)
    0
    0
        Week 2 (n=187, 189)
    0
    0
        Week 4 (n=181, 183)
    0
    0
        Week 6 (n=172, 172)
    0
    0
        Week 7 (n=167, 170)
    0
    0
        Week 8 (n=167, 169)
    0
    0
        Endpoint (n=196, 198)
    0
    0
    Notes
    [34] - Safety analysis set
    [35] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Completed Suicide Question

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    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Completed Suicide Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Completed Suicide question records whether the participant intentionally causing his/her's own death since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [36]
    200 [37]
    Units: participants
        Week 1 (n=196, 195)
    0
    0
        Week 2 (n=187, 189)
    0
    0
        Week 4 (n=181, 183)
    0
    0
        Week 6 (n=172, 172)
    0
    0
        Week 7 (n=167, 170)
    0
    0
        Week 8 (n=167, 169)
    0
    0
        Endpoint (n=196, 198)
    0
    0
    Notes
    [36] - Safety analysis set
    [37] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Wish to Be Dead Question

    Close Top of page
    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Wish to Be Dead Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Wish to Be Dead question records whether the participant endorses thoughts about a wish to dead or not alive anymore, or a wish to fall asleep and not wake up since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [38]
    200 [39]
    Units: participants
        Week 1 (n=196, 195)
    6
    5
        Week 2 (n=187, 189)
    2
    6
        Week 4 (n=181, 183)
    1
    7
        Week 6 (n=172, 172)
    2
    3
        Week 7 (n=167, 170)
    2
    2
        Week 8 (n=167, 169)
    1
    3
        Endpoint (n=196, 198)
    2
    4
    Notes
    [38] - Safety analysis set
    [39] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Non-Specific Active Suicidal Thoughts Question

    Close Top of page
    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Non-Specific Active Suicidal Thoughts Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Non-Specific Active Suicidal Thoughts question records whether the participant shares general non-specific thoughts of wanting to end one's life/commit suicide since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [40]
    200 [41]
    Units: participants
        Week 1 (n=196, 195)
    2
    0
        Week 2 (n=187, 189)
    0
    0
        Week 4 (n=181, 183)
    0
    1
        Week 6 (n=172, 172)
    0
    1
        Week 7 (n=167, 170)
    0
    1
        Week 8 (n=167, 169)
    0
    1
        Endpoint (n=196, 198)
    0
    1
    Notes
    [40] - Safety analysis set
    [41] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Any Methods (Not Plan) Without Intent to Act Question

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    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Any Methods (Not Plan) Without Intent to Act Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Any Methods (Not Plan) Without Intent to Act question records whether the participant endorses thoughts of suicide and has thought of at least one method but has no specific plan of action since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. This question is asked only if the answer to the 'Non-Specific Active Suicidal Thoughts' question was YES. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [42]
    200 [43]
    Units: participants
        Week 1 (n=6, 5)
    1
    1
        Week 2 (n=2, 6)
    0
    0
        Week 4 (n=1, 7)
    0
    0
        Week 6 (n=1, 3)
    0
    0
        Week 7 (n=2, 2)
    0
    0
        Week 8 (n=1, 3)
    0
    0
        Endpoint (n=8, 12)
    1
    0
    Notes
    [42] - Safety analysis set
    [43] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Some Intent to Act Without a Specific Plan Question

    Close Top of page
    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Some Intent to Act Without a Specific Plan Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Some Intent to Act Without a Specific Plan question records whether the participant has active suicidal thoughts of killing oneself and reports having some intent to act on such thoughts since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. This question is asked only if the answer to the 'Non-Specific Active Suicidal Thoughts' question was YES. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [44]
    200 [45]
    Units: participants
        Week 1 (n=6, 5)
    0
    0
        Week 2 (n=2, 6)
    0
    0
        Week 4 (n=1, 7)
    0
    0
        Week 6 (n=1, 3)
    0
    0
        Week 7 (n=2, 2)
    0
    0
        Week 8 (n=1, 3)
    0
    0
        Endpoint (n=8, 12)
    0
    0
    Notes
    [44] - Safety analysis set
    [45] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Specific Plan and Intent Question

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    End point title
    Columbia-Suicide Severity Rating Scale ‘Since Last Visit’ Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Specific Plan and Intent Question
    End point description
    The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Specific Plan and Intent question records whether the participant has active suicidal thoughts of killing oneself with details of plan fully or partially worked out and the participant has some intent to carry out the plan since the last visit. The safety analysis set includes randomized participants who took 1 or more doses of study drug. This question is asked only if the answer to the 'Non-Specific Active Suicidal Thoughts' question was YES. The number analyzed includes participants with treatment assessments at the indicated time period.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation
    End point values
    Placebo Armodafinil 150 mg/day
    Number of subjects analysed
    198 [46]
    200 [47]
    Units: participants
        Week 1 (n=6, 5)
    1
    0
        Week 2 (n=2, 6)
    0
    0
        Week 4 (n=1, 7)
    0
    0
        Week 6 (n=1, 3)
    0
    0
        Week 7 (n=2, 2)
    0
    0
        Week 8 (n=1, 3)
    0
    0
        Endpoint (n=8, 12)
    1
    0
    Notes
    [46] - Safety analysis set
    [47] - Safety analysis set
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 to Week 9
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    Armodafinil 150 mg/day
    Reporting group description
    Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. Treatment was administered for a total of 8 weeks.

    Reporting group title
    Placebo
    Reporting group description
    Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.

    Serious adverse events
    Armodafinil 150 mg/day Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 200 (2.50%)
    6 / 198 (3.03%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Social circumstances
    Social stay hospitalisation
         subjects affected / exposed
    1 / 200 (0.50%)
    0 / 198 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Unintended pregnancy
         subjects affected / exposed
    0 / 200 (0.00%)
    1 / 198 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 200 (0.50%)
    0 / 198 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bipolar I disorder
         subjects affected / exposed
    1 / 200 (0.50%)
    0 / 198 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 200 (0.50%)
    0 / 198 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypomania
         subjects affected / exposed
    0 / 200 (0.00%)
    1 / 198 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Insomnia
         subjects affected / exposed
    1 / 200 (0.50%)
    0 / 198 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 200 (0.00%)
    1 / 198 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 200 (0.50%)
    0 / 198 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    0 / 200 (0.00%)
    1 / 198 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis chronic
         subjects affected / exposed
    1 / 200 (0.50%)
    0 / 198 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Toxic skin eruption
         subjects affected / exposed
    0 / 200 (0.00%)
    1 / 198 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 200 (0.00%)
    1 / 198 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Armodafinil 150 mg/day Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    37 / 200 (18.50%)
    21 / 198 (10.61%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    29 / 200 (14.50%)
    15 / 198 (7.58%)
         occurrences all number
    35
    17
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    12 / 200 (6.00%)
    7 / 198 (3.54%)
         occurrences all number
    13
    7

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Sep 2011
    Amendment 1 (dated 21 September 2011) to the protocol was issued after 14 patients were enrolled into the study. Changes to the protocol were considered to have no negative impact on the safety of patients already enrolled into the study. The following major procedural changes (not all-inclusive) were made to the protocol: - In the Schedule of Procedures and Assessments, the instruction to contact the IVRS or IWRS to register a visit, from visit 3 through visit 8, was deleted. - A clarification was made, which stated that Interactive Computerized Interview for Rating the IDS-C30, administered by the qualified rater at the investigational center, must have been performed before the interactive computerized interview was performed by the patient. - βHCG serum tests were to be performed for all women, at screening, at weeks 4 and 8, or last postbaseline observation, and if clinically indicated thereafter. The qualifier “unless surgically sterile” was removed. - A revision was made to perform sensitivity analyses for the primary efficacy variable with details provided in the SAP. - In order to accommodate country-specific regulations and guidelines, text was added to the informed consent form to include the requirement for a caregiver consent form as required by national/local health authorities.
    22 Mar 2012
    Amendment 2 (dated 22 March 2012) to the protocol was issued after 50 patients were enrolled into the study. Changes to the protocol were considered to have no negative impact on the safety of patients already enrolled into the study. The following major procedural changes (not all-inclusive) were made to the protocol: - Quetiapine, commonly prescribed in the treatment of patients with depressive episodes associated with bipolar disorder, was added as a protocol-allowed mood stabilizer. Lamotrigine was added to the list of mood stabilizers that could be taken concomitantly with ziprasidone. - An exclusion criterion was rewritten to clarify that a patient with any clinically significant cutaneous drug reaction, or a history of clinically significant hypersensitivity reaction, including multiple allergies, was not eligible for the study. - Text was removed from the informed consent form, which included the requirement for a caregiver consent form, since the addition of investigational centers in countries requiring caregiver consent was no longer applicable.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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