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

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and tolerability of long term (6 months) armodafinil treatment as adjunctive therapy to mood-stabilizing medications in adults with bipolar I disorder.

Official Title
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A 6-Month, Open-Label, Flexible-Dosage (150 to 200 mg/Day) Extension Study of the Safety and Efficacy of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

Conditions
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Depression

Intervention / Treatment
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* Drug: Armodafinil


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The patient has completed 8 weeks of treatment in a Cephalon-sponsored Phase 3, double-blind study of armodafinil treatment in patients with major depression associated with bipolar I disorder. The patient met criteria for enrollment in the previous double-blind study and, in the opinion of the investigator, is in need of continued treatment for depression. During the previous double-blind study, the patient must have been taking 1 (or 2) of the following protocol-allowed mood stabilizers: lithium; valproic acid; olanzapine; quetiapine; aripiprazole; lamotrigine; risperidone; ziprasidone, (only if taken in combination with lithium, valproic acid, or lamotrigine). The following criteria must also be met: The mood stabilizers must be taken in an oral formulation, with the exception of risperidone, which can be either in an oral or long-acting injection formulation. The patient may be taking 2 protocol-allowed mood stabilizers only if 1 of the drugs is lithium, valproic acid, or lamotrigine. The patient must be judged by the investigator to be compliant with treatment with the mood stabilizer(s). The patient must be willing to continue treatment with the same protocol-allowed mood stabilizer(s) at dosages considered appropriate by the investigator. The patient has a Young Mania Rating Scale (YMRS) total score of 14 or less at the enrollment visit. Patients who have a YMRS score of 12 through 14 must be discussed with the medical monitor to determine their suitability for enrollment. Key Exclusion Criteria: The patient has any Axis I or Axis II disorder apart from bipolar I disorder that became the primary focus of treatment during the double-blind study. The patient has psychotic symptoms or had psychosis during the double-blind study. 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 met criteria for alcohol or substance abuse or dependence (with the exception of nicotine dependence) during the double-blind study. The patient has any history of homicidal ideation or significant aggression or currently has homicidal or significant aggressive ideation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Armodafinil 150-200 mg/day<br>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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months. | Drug: Armodafinil<br>* Armodafinil tablets, taken orally, once daily in the morning<br>* Other names: Nuvigil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Treatment-Emergent Adverse Events (TEAE) | 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. | Day 1 up to Month 6 | 
| Participants With Clinically Significant Abnormal Serum Chemistry Values | Summary of serum chemistry tests in which at least one participant had a during study value that was clinically significant abnormal. The test name and criterion for clinically significant abnormal appear in each row. ULN=upper limit of normal BUN=Blood Urea Nitrogen; Uric acid has a normal range of 125-494 μmol/L. Criterion for clinically significant abnormal are different for men and women. GGT = gamma-glutamyl transpeptidase with a normal range of 4-61 U/L ALT = alanine aminotransferase with a normal range of 6-43 U/L BUN = blood urea nitrogen with a normal range of 1.4-8.6 mmol/L AST = aspartate aminotransferase with a normal range of 9-36 U/L | Day 1 to Month 6 | 
| Participants With Clinically Significant Abnormal Hematology Values | Summary of hematology tests in which at least one participant had a during study value that was clinically significant abnormal. The test name and criterion for clinically significant abnormal appear in each row. ULN=upper limit of normal WBC - white blood cell counts with a normal range of 3.8-10.7 10^9/L. Hemoglobin with a normal range of 115-181 g/L Hematocrit with a normal range of 0.34-0.54 L/L Platelet counts with a normal range of 130-400 10^9/L ANC= absolute neutrophil counts with a normal range of 1.96-7.23 10^9/L | Day 1 to Month 6 | 
| Participants With Clinically Significant Abnormal Urinalysis Values | Summary of urinalysis tests in which at least one participant had a during study value that was clinically significant abnormal. Criterion for clinically significant abnormal urinalysis tests was >=2 unit increase from baseline. | Day 1 to Month 6 | 
| Participants With Clinically Significant Abnormal Vital Signs Values | Summary of vital signs tests in which at least one participant had a during study value that was clinically significant abnormal. Criterion for clinically significant abnormal vital signs are based on FDA Neuropharmacological Division criteria: Pulse high: >=120 beats per minute (bpm) and increase of >=15 bpm from baseline Pulse low: <=50 bpm and decrease of >=15 bpm from baseline Sitting systolic blood pressure high: >=180 mm Hg and increase of >=20 mm Hg from baseline Sitting systolic blood pressure low: <=90 mm Hg and decrease of >=20 mm Hg from baseline Sitting diastolic blood pressure high: >=105 mm Hg and increase of >=15 mm Hg from baseline Sitting diastolic blood pressure low: <=50 mm Hg and decrease of >=15 mm Hg from baseline | Day 1 to Month 6 | 
| Change From Baseline to Endpoint in Electrocardiogram (ECG) Values | ECG was conducted at baseline which was before the first dose of study drug in the double-blind study, and at the month-6 visit of the open-label study (or early termination). RR= inter-beat intervals | Day 0 (baseline), Month 6 or last post-baseline observation | 
| Physical Examination Shifts From Baseline to Endpoint | Baseline is the day prior to double-blind treatment. Assessments are summarized as normal or abnormal. The first assessment is the baseline assessment followed by the endpoint assessment. For example 'normal/abnormal' indicates participants who were normal at baseline and abnormal at endpoint. HEENT = Head, Eye, Ear, Nose and Throat exam | Day 0 (baseline), Month 6 (or last post-baseline observation) | 
| Change From Baseline to Endpoint in Body Weight | Baseline was the score before the first dose of study drug in the double-blind study. | Day 0 (baseline), Month 6 (or last post-baseline observation) | 
| Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score | 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. Baseline was the score before the first dose of study drug in the double-blind study. | Day 0 (baseline), Month 6 or last post-baseline observation | 
| Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) | 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 number of participants who had findings on any of the C-SSRS-SLV (SLV=since last visit) categories at any of the time frames are indicated. - C-SSRS=Columbia Suicide Severity Rating Scale | Day 1, Week 1, Months 1, 2, 4 and 6 or last post-baseline visit | 
| Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score | 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. Baseline was the assessment before the first dose of study drug in the double-blind study. | Day 0 (baseline), Month 6 (or last post-baseline observation) | 
| Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score | 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. Baseline was the score before the first dose of study drug in the double-blind study. | Day 0 (baseline), Month 6 or last post-baseline observation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (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. Negative change from baseline values indicate improvement in the severity of depression. Baseline was the score before the first dose of study drug in the double-blind study. | Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment) | 
| Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) | 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. Baseline was the score before the first dose of study drug in the double-blind study. | Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment) | 
| Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Clinical Global Impression of Severity (CGI-S) for Depression | 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. Baseline was the score before the first dose of study drug in the double-blind study. | Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment) | 
| Change From Baseline to Endpoint in the Global Assessment for Functioning (GAF) Scale | 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. Baseline was the score before the first dose of study drug in the double-blind study. | Day 0 (baseline), Month 6 or the last post-baseline assessment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar I Disorder