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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier:
NCT01305408
First received: February 25, 2011
Last updated: January 15, 2015
Last verified: January 2015
  Purpose

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 Intervention Phase
Depression
Drug: Armodafinil
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 mg/Day) as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Change From Baseline to Week 8 in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) [ Time Frame: Day 0 (baseline), Week 8 ] [ Designated as safety issue: No ]

    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:
  • Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score [ Time Frame: Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: No ]

    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.


  • Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) [ Time Frame: Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) [ Time Frame: Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression [ Time Frame: Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Weeks 4, 8 and Endpoint in the Global Assessment for Functioning (GAF) Scale [ Time Frame: Day 0 (baseline), Weeks 4, 8, and last postbaseline observation ] [ Designated as safety issue: No ]
    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.

  • Participants With Treatment-Emergent Adverse Events (TEAE) [ Time Frame: Day 1 to Week 9 ] [ Designated as safety issue: Yes ]

    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.


  • Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score [ Time Frame: Day 0 (baseline), last postbaseline observation ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score [ Time Frame: Day 0 (baseline), last postbaseline observation ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score [ Time Frame: Day 0 (baseline), last postbaseline observation ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.


  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.


  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.


  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.


  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.


  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.


  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.


  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.


  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.


  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.


  • 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 [ Time Frame: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 399
Study Start Date: March 2011
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.
Drug: Placebo
Matching placebo tablets, taken orally, once daily in the morning
Other Name: placebo
Experimental: Armodafinil 150 mg/day
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.
Drug: Armodafinil
Armodafinil tablets, taken orally, once daily in the morning
Other Names:
  • Nuvigil
  • CEP-10953

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, quetiapine, risperidone, ziprasidone (only if taken in combination with lithium, valproic acid, or lamotrigine). The following criteria must also be met:

    1. The mood stabilizer(s) must have been taken a minimum 4 weeks before the onset of the major depressive episode and still be taken at the time of the screening visit at dose or blood level considered appropriate for maintenance therapy by the patient's physician.
    2. The patient must continue to take the same mood stabilizer(s) during the screening period; no mood stabilizer may be added during the screening period.
    3. The mood stabilizer(s) must be taken for a minimum of at least 8 weeks prior to the baseline visit.
    4. The dosage of the mood stabilizer(s) must be stable for a minimum of 4 weeks prior to the baseline visit.
    5. The mood stabilizer(s) must be taken in an oral formulation, with the exception of risperidone, which can be either in an oral or long-acting injection formulation.
    6. The patient may be taking 2 protocol-allowed mood stabilizers only if 1 of the drugs is lithium, valproic acid, or lamotrigine.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01305408

  Show 130 Study Locations
Sponsors and Collaborators
Cephalon
Investigators
Study Director: Sponsor's Medical Expert Cephalon
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier: NCT01305408     History of Changes
Other Study ID Numbers: C10953/3073, 2010-023623-26
Study First Received: February 25, 2011
Results First Received: January 15, 2015
Last Updated: January 15, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Teva Pharmaceutical Industries:
Bipolar I Disorder

Additional relevant MeSH terms:
Depression
Behavioral Symptoms
Armodafinil
Modafinil
Central Nervous System Agents
Central Nervous System Stimulants
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Wakefulness-Promoting Agents

ClinicalTrials.gov processed this record on March 26, 2015