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A Study to Evaluate the Efficacy and Safety of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

Sponsor
Cephalon (Industry)
Overall Status
Completed
CT.gov ID
NCT01072929
Collaborator
(none)
433
Enrollment
40
Locations
3
Arms
26
Duration (Months)
10.8
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
433 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dosage Study to Evaluate the Efficacy and Safety of Armodafinil Treatment (150 and 200 mg/Day) as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder
Study Start Date :
Jan 1, 2010
Actual Primary Completion Date :
Mar 1, 2012
Actual Study Completion Date :
Mar 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Armodafinil 150 mg/day

Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.

Drug: Armodafinil
Doses of either 150mg/day or 200 mg/day in tablet form taken orally, once daily in the morning.
Other Names:
  • Nuvigil
  • CEP-10953

    		•
    Experimental: Armodafinil 200 mg/day

    Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.

    Drug: Armodafinil
    Doses of either 150mg/day or 200 mg/day in tablet form taken orally, once daily in the morning.
    Other Names:
  • Nuvigil
  • CEP-10953

    		•
    Placebo Comparator: Placebo

    Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.

    Drug: Placebo
    Matching Placebo, also in tablet form taken orally, once daily in the morning.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline to Week 8 in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) [Day 0 (baseline), Week 8]

      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.

    Secondary Outcome Measures

    1. Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score [Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

      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.

    2. Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

      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.

    3. Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) [Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

      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.

    4. Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) [Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

      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.

    5. Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression [Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

      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.

    6. Change From Baseline to Weeks 4, 8 and Endpoint in the Global Assessment for Functioning (GAF) Scale [Day 0 (baseline), Weeks 4, 8, and last postbaseline observation (up to 8 weeks)]

      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.

    7. Participants With Treatment-Emergent Adverse Events (TEAE) [Day 1 to Week 9]

      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.

    8. Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score [Day 0 (baseline), last postbaseline observation (up to 8 weeks)]

      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.

    9. Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score [Day 0 (baseline), last postbaseline observation (up to 8 weeks)]

      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.

    10. Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score [Day 0 (baseline), last postbaseline observation (up to 8 weeks)]

      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.

    11. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    12. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    13. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    14. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    15. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    16. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    17. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    18. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    19. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    20. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    21. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    22. 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 [Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • The patient has a diagnosis of bipolar I disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision) (DSM-IV-TR) criteria and is currently experiencing a major depressive episode.

    • Documentation that the patient has had at least 1 previous manic or mixed episode.

    • The patient has had no more than 6 mood episodes in the last year.

    • The patient's current major depressive episode must have started no less than 2 weeks and no more than 12 months prior to the screening visit. The current depressive episode must have begun after the patient's current mood stabilizer regime began.

    • The patient must have been taking 1 (or 2) of the following protocol-allowed mood stabilizers: lithium, valproic acid, lamotrigine, aripiprazole, olanzapine, risperidone, or ziprasidone (only if taken in combination with lithium or valproic acid).

    • Written informed consent is obtained.

    • The patient is a man or woman 18 through 65 years of age.

    • The patient is in good health (except for diagnosis of bipolar I disorder) as judged by the investigator, on the basis of medical and psychiatric history, medical examination, electrocardiography (ECG), serum chemistry, hematology, and urinalysis.

    • Women of childbearing potential (women who have not reached menopause, women who are less than 2 years postmenopausal, and women who are not surgically sterile) who are sexually active must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study.

    • The patient is willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol.

    • The patient has permanent accommodations and means of being contacted by the study center.

    • The patient understands that they may enroll in this clinical study only once and may not enroll in any other clinical study while participating in this trial.

    Exclusion Criteria:

    • The patient has any Axis I disorder apart from bipolar I disorder that was the primary focus of treatment within 6 months of the screening visit or during the screening period.

    • The patient has psychotic symptoms or has had psychosis within 4 weeks of the screening visit or during the screening period.

    • The patient has current active suicidal ideation, is at imminent risk of self-harm, or has a history of significant suicidal ideation or suicide attempt at any time in the past that causes concern at present.

    • The patient has a history of an eating disorder or obsessive compulsive disorder (OCD) within 6 months of the screening visit or during the screening period.

    • The patient has a history of alcohol or substance abuse or dependence (with the exception of nicotine dependence) within 3 months of the screening visit or during the screening period.

    • The patient has a history of any cutaneous drug reaction or drug hypersensitivity reaction, a history of any clinically significant hypersensitivity reaction, or a history of multiple clinically relevant allergies.

    • The patient has any clinically significant uncontrolled medical condition, treated or untreated.

    • The patient has received modafinil or armodafinil within the past 5 years, or the patient has a known sensitivity to any ingredients in the study drug tablets.

    • The patient has previously participated in a clinical study with armodafinil or has used any investigational product within 90 days of screening. The patient may not enroll in any other clinical study while participating in this study.

    • The patient has ever been treated with vagus nerve stimulation (VNS) or deep brain stimulation (DBS), or has been treated with electroconvulsive therapy (ECT) or repetitive transcranial magnetic stimulation (rTMS) within 3 months of the screening visit.

    • The patient is a pregnant or lactating woman.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Research Group Birmingham Alabama United States
    2 Southwestern Research Beverly Hills California United States
    3 Collaborative NeuroScience Network Garden Grove California United States
    4 Sun Valley Behavioral Medical Imperial California United States
    5 University of California Irvine Irvine California United States
    6 Excell Research Oceanside California United States
    7 Artemis Institute for Clinical Research San Diego California United States
    8 Clinical Innovations Inc. Santa Ana California United States
    9 Viking Clinical Research Center Temecula California United States
    10 CNS Clinical Research Group - Florida Clinical Research Cent Coral Springs Florida United States
    11 Gulfcoast Clinical Research Center Fort Myers Florida United States
    12 Sarkis Clinical Trials Gainesville Florida United States
    13 Dr. Vijapura and Assoc. Jacksonville Florida United States
    14 Fidelity Clinical Research Lauderhill Florida United States
    15 Clinical Neuroscience Solutions, Inc. Orlando Florida United States
    16 University of South Florida Tampa Florida United States
    17 Comprehensive Neuroscience, Inc Atlanta Georgia United States
    18 Northwest Behavioral Research Center Roswell Georgia United States
    19 AMR Baber Research Inc. Naperville Illinois United States
    20 American Medical Research Oak Brook Illinois United States
    21 CNS - Comprehensive Neuro Science Park Ridge Illinois United States
    22 Pharmasite Research, Inc Baltimore Maryland United States
    23 AccelRx Research Fall River Massachusetts United States
    24 Mid-America Clinical Research, LLC St. Louis Missouri United States
    25 CRI Worldwide, LLC Mount Laurel New Jersey United States
    26 Albequerque Neuroscience Albuquerque New Mexico United States
    27 Social Psychiatry Research Institute Brooklyn New York United States
    28 Eastside Comprehensive Medical Center New York New York United States
    29 Finger Lakes Clinical Research Rochester New York United States
    30 Richmond Behavioral Associates Staten Island New York United States
    31 Richard Weisler, MD and Associates Raleigh North Carolina United States
    32 Charak Clinical Research Center Beachwood Ohio United States
    33 Midwest Clinical Research Center Dayton Ohio United States
    34 Oregon Center for Clinical Investigations, Inc Salem Oregon United States
    35 Suburban Research Associates Media Pennsylvania United States
    36 Scranton Counseling Center Scranton Pennsylvania United States
    37 Carolina Clinical Trials, Inc. Charleston South Carolina United States
    38 Community Clinical Research Austin Texas United States
    39 FutureSearch Trials of Neurology Austin Texas United States
    40 Northwest Clinical Research Center Bellevue Washington United States

    Sponsors and Collaborators

    • Cephalon

    Investigators

    • Study Director: Sponsor's Medical Expert, Cephalon

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Cephalon
    ClinicalTrials.gov Identifier:
    NCT01072929
    Other Study ID Numbers:
    • C10953/3071
    • 2009-016667-11
    First Posted:
    Feb 22, 2010
    Last Update Posted:
    Apr 27, 2016
    Last Verified:
    Apr 1, 2016
    Keywords provided by Cephalon
    Bipolar I Disorder
    Additional relevant MeSH terms:
    Depression
    Depressive Disorder
    Modafinil

    Study Results

    Participant Flow

    Recruitment Details Four geographic regions that include countries with similar clinical practices. Region 1: USA and Canada Region 2: Bulgaria, Ukraine, Poland, and Serbia Region 3: Australia, France, and Spain Region 4: Argentina
    Pre-assignment Detail Participants were randomized (1:1) to receive150 mg/day armodafinil or matching placebo. The 200-mg/day armodafinil treatment group was discontinued per protocol Amendment 03. Randomization was stratified on the basis of the mood-stabilizing medication and region of the world.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Period Title: Overall Study
    STARTED 199 201 33
    Safety Population 199 198 32
    Full Analysis Population 196 197 31
    COMPLETED 155 150 24
    NOT COMPLETED 44 51 9

    Baseline Characteristics

    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day Total
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment. Total of all reporting groups
    Overall Participants 199 201 33 433
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    42.6
    (10.47)
    44.0
    (11.34)
    44.8
    (11.78)
    43.4
    (10.99)
    Sex: Female, Male (Count of Participants)
    Female
    129
    64.8%
    133
    66.2%
    26
    78.8%
    288
    66.5%
    Male
    70
    35.2%
    68
    33.8%
    7
    21.2%
    145
    33.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    28
    14.1%
    32
    15.9%
    1
    3%
    61
    14.1%
    Not Hispanic or Latino
    166
    83.4%
    167
    83.1%
    32
    97%
    365
    84.3%
    Unknown or Not Reported
    5
    2.5%
    2
    1%
    0
    0%
    7
    1.6%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    1
    3%
    1
    0.2%
    Asian
    3
    1.5%
    2
    1%
    0
    0%
    5
    1.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    0.5%
    0
    0%
    1
    0.2%
    Black or African American
    29
    14.6%
    17
    8.5%
    4
    12.1%
    50
    11.5%
    White
    163
    81.9%
    179
    89.1%
    27
    81.8%
    369
    85.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    4
    2%
    2
    1%
    1
    3%
    7
    1.6%
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    83.9
    (22.78)
    83.1
    (20.65)
    87.3
    (20.46)
    83.8
    (21.53)
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    168.4
    (10.56)
    167.2
    (9.32)
    167.2
    (7.57)
    167.8
    (9.80)
    Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    29.5
    (7.04)
    29.7
    (6.91)
    31.3
    (6.56)
    29.7
    (6.94)
    Time Since Start of Current Depressive Episode (weeks) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [weeks]
    13.7
    (10.69)
    12.9
    (9.38)
    15.2
    (10.42)
    13.4
    (10.07)
    Time Since First Diagnosis for Bipolar (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    10.9
    (8.51)
    10.6
    (8.55)
    13.7
    (10.23)
    11.0
    (8.69)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline to Week 8 in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)
    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.
    Time Frame Day 0 (baseline), Week 8

    Outcome Measure Data

    Analysis Population Description
    Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment.
    Arm/Group Title Placebo Armodafinil 150 mg/Day All Armodafinil
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
    Measure Participants 196 197 228
    Least Squares Mean (Standard Error) [units on a scale]
    -17.9
    (1.10)
    -21.7
    (1.11)
    -20.8
    (1.07)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Armodafinil 150 mg/Day
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0097
    Comments All statistical tests were 2-tailed at the 0.05 level of significance.
    Method mixed-model repeated measures (MMRM)
    Comments Treatment, visit, treatment-by-visit interaction, concurrent mood-stabilizing medication, and region of the world used as fixed factors.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.8
    Confidence Interval (2-Sided) 95%
    -6.58 to -0.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, All Armodafinil
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0385
    Comments All statistical tests were 2-tailed at the 0.05 level of significance.
    Method mixed-model repeated measures (MMRM)
    Comments Treatment, visit, treatment-by-visit interaction, concurrent mood-stabilizing medication, and region of the world used as fixed factors.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.9
    Confidence Interval (2-Sided) 95%
    -5.71 to -0.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score
    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.
    Time Frame Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. The denominator for calculating the percentages at each visit is the number of participants with a nonmissing value at that visit. Endpoint was the last observed postbaseline data.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 196 197 31
    Week 1 (191, 193, 29)
    4
    2%
    6
    3%
    10
    30.3%
    Week 2 (188, 181, 27)
    12
    6%
    8
    4%
    26
    78.8%
    Week 4 (178, 168, 27)
    23
    11.6%
    26
    12.9%
    37
    112.1%
    Week 6 (160, 158, 21)
    38
    19.1%
    39
    19.4%
    43
    130.3%
    Week 7 (152, 144, 19)
    39
    19.6%
    51
    25.4%
    47
    142.4%
    Week 8 (155, 150, 24)
    39
    19.6%
    55
    27.4%
    42
    127.3%
    Endpoint (196, 197, 31)
    34
    17.1%
    46
    22.9%
    39
    118.2%
    3. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. The denominator for calculating the percentages at each visit is the number of participants with a nonmissing value at that visit. Endpoint was the last observed postbaseline data.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 196 197 31
    Week 1 (191, 193, 29)
    1
    0.5%
    1
    0.5%
    3
    9.1%
    Week 2 (188, 181, 27)
    2
    1%
    2
    1%
    7
    21.2%
    Week 4 (178, 168, 27)
    6
    3%
    4
    2%
    11
    33.3%
    Week 6 (160, 158, 21)
    16
    8%
    15
    7.5%
    10
    30.3%
    Week 7 (152, 144, 19)
    22
    11.1%
    17
    8.5%
    16
    48.5%
    Week 8 (155, 150, 24)
    22
    11.1%
    28
    13.9%
    17
    51.5%
    Endpoint (196, 197, 31)
    17
    8.5%
    21
    10.4%
    13
    39.4%
    4. Secondary Outcome
    Title Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)
    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.
    Time Frame Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. Participants are included in the analysis at each timepoint if they have a nonmissing value at that visit. Endpoint for analyses was the last observed postbaseline data.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 196 197 31
    Week 1 (191, 193, 29)
    -6.1
    (7.46)
    -6.5
    (7.90)
    -9.8
    (8.96)
    Week 2 (188, 181, 27)
    -10.2
    (8.60)
    -10.4
    (9.08)
    -12.9
    (10.92)
    Week 4 (178, 168, 27)
    -14.3
    (11.04)
    -15.6
    (10.33)
    -15.3
    (13.09)
    Week 6 (160, 158, 21)
    -18.3
    (12.23)
    -19.7
    (10.49)
    -17.4
    (13.42)
    Week 7 (152, 144, 19)
    -18.8
    (13.27)
    -21.7
    (11.30)
    -17.8
    (14.57)
    Week 8 (155, 150, 24)
    -19.7
    (13.19)
    -23.3
    (12.22)
    -17.0
    (14.64)
    Endpoint (196, 197, 31)
    -17.3
    (14.06)
    -20.2
    (13.44)
    -15.8
    (13.55)
    5. Secondary Outcome
    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)
    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.
    Time Frame Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. The number of participants at each visit are those with a nonmissing value at that visit. Endpoint was the last observed postbaseline data.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 196 197 31
    Week 1 (191, 194, 29)
    -2.3
    (3.05)
    -2.8
    (3.53)
    -4.1
    (3.95)
    Week 2 (188, 181, 27)
    -3.8
    (3.66)
    -4.4
    (3.83)
    -5.0
    (4.80)
    Week 4 (178, 168, 27)
    -5.6
    (4.55)
    -6.5
    (4.23)
    -6.4
    (4.96)
    Week 6 (160, 158, 21)
    -6.9
    (5.01)
    -8.1
    (3.91)
    -7.4
    (5.22)
    Week 7 (152, 145, 19)
    -7.2
    (5.32)
    -8.6
    (4.16)
    -7.6
    (6.36)
    Week 8 (155, 150, 24)
    -7.6
    (5.39)
    -9.4
    (4.56)
    -7.3
    (5.56)
    Endpoint (196, 197, 31)
    -6.6
    (5.63)
    -8.0
    (5.23)
    -6.6
    (5.40)
    6. Secondary Outcome
    Title Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression
    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.
    Time Frame Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. The number of participants is those with a nonmissing value at that visit. Endpoint was the last observed postbaseline data.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 196 197 31
    Week 1 (191, 194, 29)
    -0.3
    (0.54)
    -0.4
    (0.72)
    -0.5
    (0.74)
    Week 2 (188, 181, 28)
    -0.5
    (0.68)
    -0.6
    (0.80)
    -0.5
    (0.79)
    Week 4 (178, 168, 27)
    -0.9
    (0.93)
    -0.9
    (0.94)
    -0.8
    (0.97)
    Week 6 (160, 158, 21)
    -1.2
    (1.10)
    -1.4
    (1.01)
    -0.9
    (1.14)
    Week 7 (152, 145, 19)
    -1.3
    (1.20)
    -1.6
    (1.10)
    -1.1
    (1.33)
    Week 8 (155, 150, 24)
    -1.5
    (1.27)
    -1.7
    (1.17)
    -1.3
    (1.49)
    Endpoint (196, 197, 31)
    -1.3
    (1.28)
    -1.4
    (1.26)
    -1.2
    (1.39)
    7. Secondary Outcome
    Title Change From Baseline to Weeks 4, 8 and Endpoint in the Global Assessment for Functioning (GAF) Scale
    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.
    Time Frame Day 0 (baseline), Weeks 4, 8, and last postbaseline observation (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. The number of participants is those with a nonmissing value at that visit. Endpoint was the last observed postbaseline data.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 196 197 31
    Week 4 (175, 168, 27)
    7.2
    (9.24)
    7.7
    (9.78)
    8.9
    (8.74)
    Week 8 (153, 150, 24)
    11.4
    (13.67)
    15.6
    (13.37)
    13.6
    (15.04)
    Endpoint (191, 189, 29)
    10.2
    (13.31)
    12.8
    (13.42)
    12.2
    (14.11)
    8. Secondary Outcome
    Title Participants With Treatment-Emergent Adverse Events (TEAE)
    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.
    Time Frame Day 1 to Week 9

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set includes randomized participants who took 1 or more doses of study drug.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    >=1 adverse event
    91
    45.7%
    95
    47.3%
    23
    69.7%
    Severe adverse event
    8
    4%
    6
    3%
    4
    12.1%
    Treatment-related adverse event
    44
    22.1%
    44
    21.9%
    13
    39.4%
    Deaths
    0
    0%
    0
    0%
    1
    3%
    Other serious adverse events
    5
    2.5%
    3
    1.5%
    2
    6.1%
    Withdrawn from study due to adverse events
    7
    3.5%
    11
    5.5%
    2
    6.1%
    Protocol-defined adverse events
    4
    2%
    7
    3.5%
    0
    0%
    9. Secondary Outcome
    Title Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score
    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.
    Time Frame Day 0 (baseline), last postbaseline observation (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 197 198 31
    Mean (Standard Deviation) [units on a scale]
    -1.1
    (3.37)
    -1.1
    (3.13)
    -1.0
    (2.39)
    10. Secondary Outcome
    Title Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score
    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.
    Time Frame Day 0 (baseline), last postbaseline observation (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 193 192 30
    Mean (Standard Deviation) [units on a scale]
    -4.2
    (4.69)
    -4.2
    (5.88)
    -3.3
    (4.31)
    11. Secondary Outcome
    Title Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score
    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.
    Time Frame Day 0 (baseline), last postbaseline observation (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 193 190 29
    Mean (Standard Deviation) [units on a scale]
    -6.4
    (9.93)
    -6.5
    (7.19)
    -5.6
    (6.33)
    12. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (191, 194, 29)
    0
    0%
    0
    0%
    0
    0%
    Week 2 (188, 181, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 4 (178, 168, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 6 (159, 158, 21)
    0
    0%
    0
    0%
    0
    0%
    Week 7 (152, 145, 19)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (155, 150, 24)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (197, 198, 31)
    1
    0.5%
    0
    0%
    0
    0%
    13. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (191, 194, 29)
    0
    0%
    0
    0%
    0
    0%
    Week 2 (188, 181, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 4 (178, 168, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 6 (159, 158, 21)
    0
    0%
    0
    0%
    0
    0%
    Week 7 (152, 145, 19)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (155, 150, 24)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (197, 198, 31)
    0
    0%
    0
    0%
    0
    0%
    14. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (191, 194, 29)
    0
    0%
    0
    0%
    0
    0%
    Week 2 (188, 181, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 4 (178, 168, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 6 (159, 158, 21)
    0
    0%
    0
    0%
    0
    0%
    Week 7 (152, 145, 19)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (155, 150, 24)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (197, 198, 31)
    0
    0%
    0
    0%
    0
    0%
    15. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (191, 194, 29)
    0
    0%
    0
    0%
    0
    0%
    Week 2 (188, 181, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 4 (178, 168, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 6 (159, 158, 21)
    0
    0%
    0
    0%
    0
    0%
    Week 7 (152, 145, 19)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (155, 150, 24)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (197, 198, 31)
    0
    0%
    0
    0%
    0
    0%
    16. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (191, 194, 29)
    0
    0%
    0
    0%
    0
    0%
    Week 2 (188, 181, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 4 (178, 168, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 6 (159, 158, 21)
    0
    0%
    0
    0%
    0
    0%
    Week 7 (152, 145, 19)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (155, 150, 24)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (197, 198, 31)
    1
    0.5%
    0
    0%
    0
    0%
    17. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (191, 194, 29)
    0
    0%
    0
    0%
    0
    0%
    Week 2 (188, 181, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 4 (178, 168, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 6 (159, 158, 21)
    0
    0%
    0
    0%
    0
    0%
    Week 7 (152, 145, 19)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (155, 150, 24)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (197, 198, 31)
    1
    0.5%
    0
    0%
    0
    0%
    18. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (191, 194, 29)
    0
    0%
    0
    0%
    0
    0%
    Week 2 (188, 181, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 4 (178, 168, 27)
    0
    0%
    0
    0%
    0
    0%
    Week 6 (159, 158, 21)
    0
    0%
    0
    0%
    0
    0%
    Week 7 (152, 145, 19)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (155, 150, 24)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (197, 198, 31)
    0
    0%
    0
    0%
    0
    0%
    19. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (191, 194, 29)
    4
    2%
    7
    3.5%
    1
    3%
    Week 2 (188, 181, 27)
    2
    1%
    4
    2%
    0
    0%
    Week 4 (178, 168, 27)
    3
    1.5%
    5
    2.5%
    0
    0%
    Week 6 (159, 158, 21)
    0
    0%
    5
    2.5%
    0
    0%
    Week 7 (152, 145, 19)
    1
    0.5%
    0
    0%
    0
    0%
    Week 8 (155, 150, 24)
    1
    0.5%
    2
    1%
    0
    0%
    Endpoint (197, 198, 31)
    6
    3%
    7
    3.5%
    0
    0%
    20. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (191, 194, 29)
    1
    0.5%
    1
    0.5%
    1
    3%
    Week 2 (188, 181, 27)
    0
    0%
    1
    0.5%
    0
    0%
    Week 4 (178, 168, 27)
    0
    0%
    1
    0.5%
    0
    0%
    Week 6 (159, 158, 21)
    0
    0%
    1
    0.5%
    0
    0%
    Week 7 (152, 145, 19)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (155, 150, 24)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (197, 198, 31)
    0
    0%
    3
    1.5%
    0
    0%
    21. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set includes randomized participants who took 1 or more doses of study drug. This question is asked if the answer to the 'Non-Specific Active Suicidal Thoughts' question was YES, or based on the judgment of the assessor. The number analyzed includes participants with treatment assessments at the indicated time period.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (3, 6, 1)
    1
    0.5%
    0
    0%
    0
    0%
    Week 2 (2, 2, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 4 (2, 4, 0)
    0
    0%
    1
    0.5%
    0
    0%
    Week 6 (0, 2, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 7 (1, 0, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (0, 2, 0)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (11, 11, 1)
    1
    0.5%
    3
    1.5%
    0
    0%
    22. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set includes randomized participants who took 1 or more doses of study drug. This question is asked if the answer to the 'Non-Specific Active Suicidal Thoughts' question was YES, or based on the judgment of the assessor. The number analyzed includes participants with treatment assessments at the indicated time period.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (3, 6, 1)
    0
    0%
    0
    0%
    0
    0%
    Week 2 (2, 2, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 4 (2, 4, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 6 (0, 2, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 7 (1, 0, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (0, 2, 0)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (11, 11, 1)
    0
    0%
    0
    0%
    0
    0%
    23. Secondary Outcome
    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
    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.
    Time Frame Weeks 1, 2, 4, 6, 7, 8, and Endpoint (up to 8 weeks)

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set includes randomized participants who took 1 or more doses of study drug. This question is asked if the answer to the 'Non-Specific Active Suicidal Thoughts' question was YES, or based on the judgment of the assessor. The number analyzed includes participants with treatment assessments at the indicated time period.
    Arm/Group Title Placebo Armodafinil 150 mg/Day Armodafinil 200 mg/Day
    Arm/Group Description Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
    Measure Participants 199 198 32
    Week 1 (3, 6, 1)
    0
    0%
    0
    0%
    0
    0%
    Week 2 (2, 2, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 4 (2, 4, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 6 (0, 2, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 7 (1, 0, 0)
    0
    0%
    0
    0%
    0
    0%
    Week 8 (0, 2, 0)
    0
    0%
    0
    0%
    0
    0%
    Endpoint (11, 11, 1)
    1
    0.5%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame Day 1 to Week 9
    Adverse Event Reporting Description
    Arm/Group Title ARMODAFINIL 150 MG ARMODAFINIL 200 MG PLACEBO
    Arm/Group Description Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment. Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.
    All Cause Mortality
    ARMODAFINIL 150 MG ARMODAFINIL 200 MG PLACEBO
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    ARMODAFINIL 150 MG ARMODAFINIL 200 MG PLACEBO
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/198 (1.5%) 2/32 (6.3%) 5/199 (2.5%)
    General disorders
    Chest pain 0/198 (0%) 0 0/32 (0%) 0 1/199 (0.5%) 1
    Irritability 1/198 (0.5%) 1 0/32 (0%) 0 0/199 (0%) 0
    Hepatobiliary disorders
    Acute hepatic failure 0/198 (0%) 0 1/32 (3.1%) 1 0/199 (0%) 0
    Hepatitis acute 0/198 (0%) 0 1/32 (3.1%) 1 0/199 (0%) 0
    Injury, poisoning and procedural complications
    Intentional overdose 0/198 (0%) 0 0/32 (0%) 0 2/199 (1%) 2
    Psychiatric disorders
    Aggression 1/198 (0.5%) 1 0/32 (0%) 0 0/199 (0%) 0
    Depression 0/198 (0%) 0 0/32 (0%) 0 3/199 (1.5%) 3
    Depressive symptom 1/198 (0.5%) 2 0/32 (0%) 0 0/199 (0%) 0
    Psychotic disorder 2/198 (1%) 2 0/32 (0%) 0 0/199 (0%) 0
    Suicidal ideation 2/198 (1%) 3 0/32 (0%) 0 0/199 (0%) 0
    Suicide attempt 0/198 (0%) 0 0/32 (0%) 0 1/199 (0.5%) 1
    Other (Not Including Serious) Adverse Events
    ARMODAFINIL 150 MG ARMODAFINIL 200 MG PLACEBO
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 41/198 (20.7%) 15/32 (46.9%) 44/199 (22.1%)
    Gastrointestinal disorders
    Diarrhoea 17/198 (8.6%) 18 2/32 (6.3%) 3 13/199 (6.5%) 13
    Nausea 11/198 (5.6%) 13 3/32 (9.4%) 3 9/199 (4.5%) 11
    General disorders
    Feeling jittery 1/198 (0.5%) 1 2/32 (6.3%) 2 1/199 (0.5%) 1
    Nervous system disorders
    Headache 19/198 (9.6%) 27 7/32 (21.9%) 8 20/199 (10.1%) 25
    Migraine 0/198 (0%) 0 2/32 (6.3%) 3 1/199 (0.5%) 1
    Psychiatric disorders
    Insomnia 8/198 (4%) 14 4/32 (12.5%) 4 8/199 (4%) 8

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.

    Results Point of Contact

    Name/Title Director, Clinical Research
    Organization Teva Branded Pharmaceutical Products, R&D Inc.
    Phone 215-591-3000
    Email ustevatrials@tevapharm.com
    Responsible Party:
    Cephalon
    ClinicalTrials.gov Identifier:
    NCT01072929
    Other Study ID Numbers:
    • C10953/3071
    • 2009-016667-11
    First Posted:
    Feb 22, 2010
    Last Update Posted:
    Apr 27, 2016
    Last Verified:
    Apr 1, 2016