Efficacy and Tolerability of Armodafinil in Adults With Excessive Sleepiness Associated With Shift Work Disorder

Study Overview
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Brief Summary
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The primary objective of the study is to determine whether armodafinil treatment is more effective than placebo treatment in patients with excessive sleepiness associated with shift work disorder (SWD) by measuring improved clinical condition late in the shift, including the commute home.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Tolerability of Armodafinil Treatment (150 mg) in Improving Clinical Condition Late in the Shift and in Improving Functional and Patient-Reported Outcomes in Adult Patients With Excessive Sleepiness Associated With Shift Work Disorder

Conditions
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Excessive Sleepiness

Intervention / Treatment
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* Drug: Armodafinil
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient currently meets the criteria for Shift Work Disorder (SWD) for duration of at least 1 month. The patient has the presence of excessive sleepiness late in the shift, including the commute home if applicable, with a Clinical Global Impression of Severity of Illness (CGI-S) rating of 4 or more at screening. The patient has clinically significant difficulty in social or occupational functioning, with a Global Assessment of Function (GAF) score less than 70 (on clinician interview) at screening. The patient has a Karolinska Sleepiness Scale (KSS) score of 6 or more at screening (visit 1) that is confirmed at baseline (visit 2). The patient works at least 5 night shifts per month, of which at least 3 nights are consecutive, and plans to maintain this schedule. The patient works night shifts or rotating shifts that include at least 6 hours between 2200 and 0800 (including the time period 0400 to 0800), and shifts are no longer than 12 hours in duration. The patient is in good health, as judged by the investigator. The patient is able to complete self-rating scales. Women of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception, and must continue use of 1 of these methods for the duration of the study (and for 30 days after participation in the study). Acceptable methods of contraception include: abstinence, barrier method with spermicide, steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method, or intrauterine device (IUD). The patient is willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol Exclusion Criteria: The patient has mild or more severe obstructive sleep apnea (OSA) defined as an apnea/hypopnea index more than 5 as determined by daytime polysomnography (PSG). The patient has a medical or psychiatric disorder causing clinically significant functional impairment or contributing to the patient's excessive sleepiness. The patient is currently taking a medication or substance that is causing clinically significant functional impairment or contributing to the patient's excessive sleepiness. The patient has a clinically significant treated or untreated medical condition. The patient has a history of clinically significant suicidal ideation in the judgment of the principal investigator or is currently suicidal based on medical and psychiatric history. The patient has a known hypersensitivity to armodafinil, racemic modafinil, or any component of the study drug tablets. The patient has a history of any clinically significant cutaneous drug reaction, or a history of clinically significant hypersensitivity reaction, including multiple allergies or drug reactions. The patient consumes caffeine including coffee, tea and/or other caffeine containing beverages or food averaging more than 600 mg of caffeine per day within 7 days of the baseline visit. The patient uses any prescription or over-the-counter (OTC) drugs disallowed by the protocol within 30 days of the baseline visit. The patient has been in a prior armodafinil study. The patient has a history of alcohol, narcotic, or any other drug abuse. The patient has a positive urine drug screen (UDS) without medical explanation at the screening visit. The patient has a clinically significant deviation from normal on physical examination. The patient is a pregnant or lactating woman. The patient has used an investigational drug within 1 month of the screening visit. The patient has a disorder that could interfere with the absorption, distribution, metabolism, or excretion of the investigational product. The patient needs to use any of the excluded medications in this protocol.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 150 mg/day armodafinil<br> | Drug: Armodafinil<br>* At the baseline visit, patients who continued to meet eligibility criteria were randomly assigned (1:1) to receive either 150 mg of armodafinil or matching placebo treatment only on nights worked for 6 weeks. Study drug was taken once nightly, 30 to 60 minutes prior to the start of the night shift, on nights worked. Armodafinil treatment was titrated as follows (only on nights worked): the first dose was 50 mg (1 tablet), the second and third doses were 100 mg (2 tablets), and the fourth and subsequent doses were 150 mg (3 tablets). Placebo tablets matching armodafinil tablets were administered on the same schedule.<br>* Other names: CEP-10953;|
| Placebo Comparator: Matching placebo<br> | Drug: Matching Placebo<br>* At the baseline visit, patients who continued to meet eligibility criteria were randomly assigned (1:1) to receive either 150 mg of armodafinil or matching placebo treatment only on nights worked for 6 weeks. Study drug was taken once nightly, 30 to 60 minutes prior to the start of the night shift, on nights worked. Armodafinil treatment was titrated as follows (only on nights worked): the first dose was 50 mg (1 tablet), the second and third doses were 100 mg (2 tablets), and the fourth and subsequent doses were 150 mg (3 tablets). Placebo tablets matching armodafinil tablets were administered on the same schedule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With at Least Minimal Improvement From Baseline in the Clinical Global Impression of Change (CGI-C) Rating as Related to Late Shift Sleepiness at Endpoint | The Clinical Global Impression of Change (CGI-C) is an assessment performed by the clinician, evaluating the change in the patient's symptoms over time. The clinician categorizes the change as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. The data presented here represents the percentage of patients whose condition showed at least minimal improvement in the CGI-C rating as related to late shift sleepiness (defined as the period 0400-0800, including the commute home). | Baseline and week 6 (or last observation after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Endpoint in Global Assessment of Function (GAF) Score | The Global Assessment of Functioning (GAF) is a numeric scale (0 through 100) used by the clinician to rate the social, occupational, and psychological functioning of the patient. A higher score indicates superior functioning and fewer symptoms. The data presented here represents the mean change from baseline to endpoint in the GAF scores of each group. | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Week 3 in Global Assessment of Functioning | The Global Assessment of Functioning (GAF) is a numeric scale (0 through 100) used by the clinician to rate the social, occupational, and psychological functioning of the patient. A higher score indicates superior functioning and fewer symptoms. The data presented here represents the mean change from baseline in the GAF scores of each group. | Baseline and Week 3 | 
| Change From Baseline to Week 6 in Global Assessment of Functioning | The Global Assessment of Functioning (GAF) is a numeric scale (0 through 100) used by the clinician to rate the social, occupational, and psychological functioning of the patient. A higher score indicates superior functioning and fewer symptoms. The data presented here represents the mean change from baseline in the GAF scores of each group. | Baseline and Week 6 | 
| Change From Baseline to Endpoint in the Mean Karolinska Sleepiness Scale (KSS) Score | The Karolinska sleepiness scale is a 10-point scale, on which the participant has to mark his sleepiness during the previous 10 minutes. The scale ranges from 1, which indicates extremely alert, to 10, which indicates extremely sleepy, can't stay awake. The KSS was performed by the participant at the baseline visit, week 3, and week 6 (or early termination visit). The score recorded is the average of 3 assessments within ±15 minutes at 0400, 0600, and 0800. The data presented here represents the mean change from baseline in the KSS scores of each group. | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Week 3 in the Mean Karolinska Sleepiness Scale (KSS) Score | The Karolinska sleepiness scale is a 10-point scale, on which the participant has to mark his sleepiness during the previous 10 minutes. The scale ranges from 1, which indicates extremely alert, to 10, which indicates extremely sleepy, can't stay awake. The KSS was performed by the participant at the baseline visit, week 3, and week 6 (or early termination visit). The score recorded is the average of 3 assessments within ±15 minutes at 0400, 0600, and 0800. The data presented here represents the mean change from baseline in the KSS scores of each group. | Baseline and week 3 | 
| Change From Baseline to Week 6 in the Mean Karolinska Sleepiness Scale (KSS) Score | The Karolinska sleepiness scale is a 10-point scale, on which the participant has to mark his sleepiness during the previous 10 minutes. The scale ranges from 1, which indicates extremely alert, to 10, which indicates extremely sleepy, can't stay awake. The KSS was performed by the participant at the baseline visit, week 3, and week 6 (or early termination visit). The score recorded is the average of 3 assessments within ±15 minutes at 0400, 0600, and 0800. The data presented here represents the mean change from baseline in the KSS scores of each group. | Baseline and week 6 | 
| Percentage of Patients With at Least Minimal Improvement From Baseline in the Clinical Global Impression of Change (CGI-C) Rating as Related to Late Shift Sleepiness at Week 3 | The Clinical Global Impression of Change (CGI-C) is an assessment performed by the clinician, evaluating the change in the patient's symptoms over time. The clinician categorizes the change as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. The data presented here represents the percentage of patients whose condition showed at least minimal improvement in the CGI-C rating as related to late shift sleepiness (defined as the period 0400-0800, including the commute home). | Baseline and week 3 | 
| Percentage of Patients With at Least Minimal Improvement From Baseline in the Clinical Global Impression of Change (CGI-C) Rating as Related to Late Shift Sleepiness at Week 6 | The Clinical Global Impression of Change (CGI-C) is an assessment performed by the clinician, evaluating the change in the patient's symptoms over time. The clinician categorizes the change as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. The data presented here represents the percentage of patients whose condition showed at least minimal improvement in the CGI-C rating as related to late shift sleepiness (defined as the period 0400-0800, including the commute home). | Baseline and week 6 | 
| Change From Baseline to Endpoint in the Modified Sheehan Disability Scale (MSDS) Composite Score | Mental-health related disability was assessed with the Modified Sheehan Disability Scale (MSDS). The MSDS has three 11-point items, and the participant is asked to rate, on a numerical scale, the extent to which emotional problems have disrupted her/his work, social life, and family life/home responsibilities over the last month. Each item is rated from 0, indicating not at all, to 10, indicating extremely. Scores for the items are summed for a possible score of 0 to 30. The MSDS was performed by the patient at the baseline visit, at Week 3, and at Week 6. | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Endpoint in the Modified Sheehan Disability Scale (MSDS) Work Item Score | Mental-health related disability was assessed with the Modified Sheehan Disability Scale (MSDS). The MSDS has three 11-point items, and the participant is asked to rate, on a numerical scale, the extent to which emotional problems have disrupted her/his work, social life, and family life/home responsibilities over the last month. Each item is rated from 0, indicating not at all, to 10, indicating extremely. Scores for the items are summed for a possible score of 0 to 30. The MSDS was performed by the patient at the baseline visit, at Week 3, and at Week 6. | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Endpoint in the Modified Sheehan Disability Scale (MSDS) Social Life Item Score | Mental-health related disability was assessed with the Modified Sheehan Disability Scale (MSDS). The MSDS has three 11-point items, and the participant is asked to rate, on a numerical scale, the extent to which emotional problems have disrupted her/his work, social life, and family life/home responsibilities over the last month. Each item is rated from 0, indicating not at all, to 10, indicating extremely. Scores for the items are summed for a possible score of 0 to 30. The MSDS was performed by the patient at the baseline visit, at Week 3, and at Week 6. | Baseline and week 6 (or last observation (or last observation after baseline)) | 
| Change From Baseline to Endpoint in the Modified Sheehan Disability Scale (MSDS) Family Life Item Score | Mental-health related disability was assessed with the Modified Sheehan Disability Scale (MSDS). The MSDS has three 11-point items, and the participant is asked to rate, on a numerical scale, the extent to which emotional problems have disrupted her/his work, social life, and family life/home responsibilities over the last month. Each item is rated from 0, indicating not at all, to 10, indicating extremely. Scores for the items are summed for a possible score of 0 to 30. The MSDS was performed by the patient at the baseline visit, at Week 3, and at Week 6. | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Endpoint in the Modified Sheehan Disability Scale (MSDS) Score - Days Missed Work or Unable to Carry Out Responsibilities | Mental-health related disability was assessed with the Modified Sheehan Disability Scale (MSDS). The MSDS has three 11-point items, and the participant is asked to rate, on a numerical scale, the extent to which emotional problems have disrupted her/his work, social life, and family life/home responsibilities over the last month. Each item is rated from 0, indicating not at all, to 10, indicating extremely. Scores for the items are summed for a possible score of 0 to 30. The MSDS was performed by the patient at the baseline visit, at Week 3, and at Week 6. | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Endpoint in the Modified Sheehan Disability Scale (MSDS) Score - Number of Days of Reduced Productivity | Mental-health related disability was assessed with the Modified Sheehan Disability Scale (MSDS). The MSDS has three 11-point items, and the participant is asked to rate, on a numerical scale, the extent to which emotional problems have disrupted her/his work, social life, and family life/home responsibilities over the last month. Each item is rated from 0, indicating not at all, to 10, indicating extremely. Scores for the items are summed for a possible score of 0 to 30. The MSDS was performed by the patient at the baseline visit, at Week 3, and at Week 6. | Baseline and week 6 (or last observation after baseline) | 
| Treatment Satisfaction Questionnaire for Medication (TSQM)- Effectiveness Score at Endpoint | TSQM is a 14 question questionnaire assessing satisfaction with the medication. 4 scales are generated: side effects, effectiveness, convenience, and global satisfaction. Subjects responded to the questionnaire at Week 3, Week 6, and last observation after baseline. Optional responses are: Extremely Dissatisfied, Very Dissatisfied, Dissatisfied, Somewhat Satisfied, Satisfied, Very Satisfied, and Extremely Satisfied. From the responses, a scale score from 0 - 100 is calculated, with a higher score indicating greater satisfaction. Results from the Effectiveness scale are presented here. | Endpoint | 
| Treatment Satisfaction Questionnaire for Medication (TSQM)- Side Effects Score at Endpoint | TSQM is a 14 question questionnaire assessing satisfaction with the medication. 4 scales are generated: side effects, effectiveness, convenience, and global satisfaction. Subjects responded to the questionnaire at Week 3, Week 6, and last post-baseline observation. Optional responses are: Extremely Dissatisfied, Very Dissatisfied, Dissatisfied, Somewhat Satisfied, Satisfied, Very Satisfied, and Extremely Satisfied. From the responses, a scale score from 0 - 100 is calculated, with a higher score indicating greater satisfaction. Results from the Side Effects scale are presented here. | Endpoint | 
| Treatment Satisfaction Questionnaire for Medication (TSQM)- Convenience Score at Endpoint | TSQM is a 14 question questionnaire assessing satisfaction with the medication. 4 scales are generated: side effects, effectiveness, convenience, and global satisfaction. Subjects responded to the questionnaire at Week 3, Week 6, and last observation after baseline. Optional responses are: Extremely Dissatisfied, Very Dissatisfied, Dissatisfied, Somewhat Satisfied, Satisfied, Very Satisfied, and Extremely Satisfied. From the responses, a scale score from 0 - 100 is calculated, with a higher score indicating greater satisfaction. Results from the Convenience scale are presented here. | Endpoint | 
| Treatment Satisfaction Questionnaire for Medication (TSQM)- Global Satisfaction Score at Endpoint | TSQM is a 14 question questionnaire assessing satisfaction with the medication. 4 scales are generated: side effects, effectiveness, convenience, and global satisfaction. Subjects responded to the questionnaire at Week 3, Week 6, and last observation after baseline. Optional responses are: Extremely Dissatisfied, Very Dissatisfied, Dissatisfied, Somewhat Satisfied, Satisfied, Very Satisfied, and Extremely Satisfied. From the responses, a scale score from 0 - 100 is calculated, with a higher score indicating greater satisfaction. Results from the Global Satisfaction scale are presented here. | Endpoint | 
| Change From Baseline to Endpoint in the Functional Outcomes of Sleep Questionnaire (FOSQ-10) Total Score | FOSQ-10 consists of 10 questions, on a scale of 1-4(1=extreme difficulty 4=no difficulty), measures impact of sleepiness on activities of daily living. Lower score = more difficulty with activity due to lack of sleep. Total score = MEAN of subscale scores (vigilance, productivity, social outcome, intimacy, activity) multiplied by 5. Worst total score is 5 (maximum difficulty) the best is 20 (no difficulty). This data reports CHANGE in total score from baseline to endpoint, with higher (positive) values representing improvement. Worst possible CHANGE value would be -15 best would be +15. | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Endpoint in the Functional Outcomes of Sleep Questionnaire (FOSQ-10) Activity Level Score | FOSQ-10 consists of 10 questions rated on a scale of 1 to 4 (1=extreme difficulty and 4=no difficulty), and is used to measure the impact of daytime sleepiness on activities of daily living and quality of life. A total score and 5 subscale (vigilance, general productivity, social outcome, intimacy, and activity level) scores are calculated from the responses. Worst subscale score is 1 (maximum difficulty) and the best score is 4 (no difficulty). This score represents the CHANGE from Baseline in the Activity level subscale. Positive change scores represent improvement (possible range -3 to +3). | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Endpoint in the Functional Outcomes of Sleep Questionnaire (FOSQ-10) General Productivity Score | FOSQ-10 consists of 10 questions rated on a scale of 1-4 (1=extreme difficulty, 4=no difficulty), and is used to measure the impact of daytime sleepiness on activities of daily living and quality of life. A total score and 5 subscale (vigilance, general productivity, social outcome, intimacy, and activity level) scores are calculated from the responses. Worst subscale score is 1 (maximum difficulty) and the best score is 4 (no difficulty). This score represents the CHANGE from Baseline in the General Productivity subscale. Positive change scores represent improvement (possible range -3 to +3). | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Endpoint in the Functional Outcomes of Sleep Questionnaire (FOSQ-10) Vigilance Score | FOSQ-10 consists of 10 questions rated on a scale of 1-4 (1=extreme difficulty, 4=no difficulty), and is used to measure the impact of daytime sleepiness on activities of daily living and quality of life. A total score and 5 subscale (vigilance, general productivity, social outcome, intimacy, and activity level) scores are calculated from the responses. Worst subscale score is 1 (maximum difficulty) and the best score is 4 (no difficulty). This score represents the CHANGE from Baseline in the Vigilance subscale. Positive change scores represent improvement (possible range -3 to +3). | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Endpoint in the Functional Outcomes of Sleep Questionnaire (FOSQ-10) Social Outcome | FOSQ-10 consists of 10 questions rated on a scale of 1-4 (1=extreme difficulty, 4=no difficulty), and is used to measure the impact of daytime sleepiness on activities of daily living and quality of life. A total score and 5 subscale (vigilance, general productivity, social outcome, intimacy, and activity level) scores are calculated from the responses. Worst subscale score is 1 (maximum difficulty) and the best score is 4 (no difficulty). This score represents the CHANGE from Baseline in the Social Outcome subscale. Positive change scores represent improvement (possible range -3 to +3). | Baseline and week 6 (or last observation after baseline) | 
| Change From Baseline to Endpoint in the Functional Outcomes of Sleep Questionnaire (FOSQ-10) Intimacy | FOSQ-10 consists of 10 questions rated on a scale of 1-4 (1=extreme difficulty, 4=no difficulty), and is used to measure the impact of daytime sleepiness on activities of daily living and quality of life. A total score and 5 subscale (vigilance, general productivity, social outcome, intimacy, and activity level) scores are calculated from the responses. Worst subscale score is 1 (maximum difficulty) and the best score is 4 (no difficulty). This score represents the CHANGE from Baseline in the Intimacy subscale. Positive change scores represent improvement (possible range -3 to +3). | Baseline and week 6 (or last observation after baseline) |