Binge Eating Disorder
Conditions
Brief summary
To evaluate maintenance of efficacy based on time to relapse between SPD489 (50 or 70mg) and placebo, as measured by the number of binge days (defined as days during which at least 1 binge episode occurs) per week as assessed by clinical interview based on subject diary and Clinical Global Impression - Severity (CGI-S) scores for patients who responded to SPD489 by the end of the Open-label Treatment Phase.
Interventions
DRUGLisdexamfetamine dimesylate
SDP489 30, 50, or 70mg capsule once per day (open-label and double-blind periods)
OTHERPlacebo
Placebo capsule once per day (double-blind period)
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is between 18-55 years of age, inclusive. 2. Subject meets the following criteria for a diagnosis of BED: * Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following: eating, in a discrete period of time (eg, within a 2-hour period) an amount of food that is definitely larger than most people would eat in a similar period of time under similar conditions, and a sense of lack of control over the eating (eg, a feeling that one cannot stop eating or control what or how much one is eating). * The binge eating episodes are associated with at least 3 of the following: eating much more rapidly than normal; eating until uncomfortably full; eating large amounts of food when not feeling physically hungry; eating alone because of being embarrassed by how much one is eating; feeling disgusted with oneself, depressed, or feeling very guilty after overeating. * Marked distress regarding binge eating. * The binge eating occurs, on average, at least 2 days a week for 6 months. * The episodes of binge eating do not occur exclusively during the course of bulimia nervosa or anorexia nervosa. 3. Subject is consistently able to swallow a capsule.
Exclusion criteria
1. Subject has current diagnosis of bulimia nervosa or anorexia nervosa. 2. Subject is receiving psychotherapy or weight loss support within the past 3 months. 3. Subject has used psychostimulants to facilitate fasting or dieting within the past 6 months. 4. Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease. 5. Subject has abnormal thyroid function. 6. Subject initiated treatment with a lipid lowering medication within the past 3 months. 7. Subject has a history of moderate or severe hypertension. 8. Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder. 9. Subject has glaucoma. 10. Subject is female and pregnant or nursing. 11. Subjects who have had bariatric surgery, lap bands, duodenal stents, or other procedures for weight loss.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Relapse From Date of Randomization to Endpoint of The Randomized-withdrawal Period | Visit 21 (26 weeks after randomization [Week 38] or Early Termination) | Relapse status was assessed during the double-blind treatment phase and was defined as having 2 or more binge days per week for 2 consecutive weeks (14 consecutive days) prior to any visit and having an increase in Clinical Global Impressions-Severity (CGI-S) score of 2 or more points compared to the randomized-withdrawal baseline (date of relapse - date of randomization). Binge eating information was captured via a self-report paper diary. The binge diary captured the number of binges per day, total hours per day spent binging, type of binge (at mealtime or at another time other than mealtime), and a description of the binge (amounts and types of foods). Binge frequency was reviewed by the clinician with the subject to confirm reported binge episodes per day. The CGI-S was performed to rate the severity of a subject's condition using a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Visit 21 (26 weeks after randomization [Week 38] or Early Termination) | The CGI-S permits a global evaluation of a subject's condition and severity of symptoms. The CGI-S was performed to rate the severity of a subject's condition based on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill). |
| Change From Randomized-Withdrawal Baseline in The Total Score of The Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) During The Randomized-withdrawal Period | Randomized-withdrawal baseline (Visit 8; 12 weeks after start of open-label treatment [Week 12]), Visit 21 (26 weeks after randomization [Week 38]) | The Y-BOCS-BE measures the obsession of binge eating thoughts and compulsiveness of binge eating behaviors. The scale is a clinician rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms). The scale includes questions regarding the amount of time spent on obsessions, impairment or distress experienced, and resistance and control over these thoughts. The same types of questions were asked about compulsions (ie, time spent, interference, etc.).Total scores range from 0 to 40. A total score of 0-7 is sub-clinical, 8-15 is mild, 16-23 is moderate, 24-31 is severe, and 32-40 is extreme. A decrease from baseline in Y-BOCS-BE Total Score represents an improvement in obsession with binge-eating thoughts or compulsiveness of binge-eating behaviors. |
| Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Mobility at Endpoint of The Open-label Period | Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination) | The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. |
| Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | Visit 21 (26 weeks after randomization [Week 38] or Early Termination) | The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. |
| Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Open-label Period | Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination) | The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. |
| Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | Visit 21 (26 weeks after randomization [Week 38] or Early Termination) | The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. |
| Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Open-label Period | Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination) | The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. |
| Change From Randomized-Withdrawal Baseline in The Number of Binge- Eating Days Per Week During The Randomized-withdrawal Period | Randomized--withdrawal baseline (Visit 8; 12 weeks after start of open- label treatment [Week 12]), Visit 21 (26 weeks after randomization [Week 38]) | A binge day was defined as days during which at least 1 binge episode occurred. As assessed by clinical interview based on subject binge diary. Binge eating information was captured via a self-report paper diary. The binge diary captured the number of binges per day, total hours per day spent binging, type of binge (at mealtime or at another time other than mealtime), and a description of the binge (amounts and types of foods). Binge frequency was reviewed by the clinician with the subject to confirm reported binge episodes per day. A negative change from Baseline indicates that binge-related behavior decreased. The randomized -withdrawal-baseline was defined as the weekly average number of binge days for the 14 days prior to the Randomization Visit (Visit 8). |
| Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Open-label Period | Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination) | The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. |
| Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | Visit 21 (26 weeks after randomization [Week 38] or Early Termination) | The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. |
| Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Open-label Period | Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination) | The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. |
| Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | Visit 21 (26 weeks after randomization [Week 38] or Early Termination) | The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. |
| Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Open-label Period | Visit 8 (12 weeks after start of open-label treatment [Week 12]) | The C-SSRS is a semistructured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answer to the first 2 ideation questions was yes, the clinician asked questions 3-5. Active suicidal ideation included any participant who answered yes to questions 2-5. If the answers to ideation questions 1 and 2 were No, then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide. |
| Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Randomized-withdrawal Period | Visit 21 (26 weeks after randomization [Week 38] or Early Termination) | The C-SSRS is a semistructured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answer to the first 2 ideation questions was yes, the clinician asked questions 3-5. Active suicidal ideation included any participant who answered yes to questions 2-5. If the answers to ideation questions 1 and 2 were No, then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide. |
| Total Scores For The Amphetamine Cessation Symptom Assessment (ACSA) Scale During Follow-up | Visit 21 (26 weeks after randomization [Week 38] or Early Termination) and Visit 22 (7 days post last dose) | The ACSA was used in this study to assess potential withdrawal symptoms associated with chronic use of SPD489. The ACSA is a self-completed scale used to assess withdrawal symptoms. The scale has 16 symptom items rated on a 5-point scale ranging from 0 (not at all) to 4 (extremely). The ACSA total score ranges from 0-64, where a higher score indicates greater withdrawal symptom severity. |
| Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | Visit 21 (26 weeks after randomization [Week 38] or Early Termination) | The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health. |
Countries
Canada, Germany, Spain, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-label Safety Population The Open-label Safety Population included all participants who had taken at least 1 dose of SPD489 in the open-label period and who had a post-baseline safety assessment. | 411 |
| Total | 411 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open-label Period (Non-randomized) | Adverse Event | 22 | 0 | 0 |
| Open-label Period (Non-randomized) | Failure to Meet Randomization Criteria | 48 | 0 | 0 |
| Open-label Period (Non-randomized) | Lost to Follow-up | 20 | 0 | 0 |
| Open-label Period (Non-randomized) | Other | 13 | 0 | 0 |
| Open-label Period (Non-randomized) | Pregnancy | 1 | 0 | 0 |
| Open-label Period (Non-randomized) | Protocol Violation | 10 | 0 | 0 |
| Open-label Period (Non-randomized) | Withdrawal by Subject | 29 | 0 | 0 |
| Randomized-withdrawal Period | Adverse Event | 0 | 0 | 6 |
| Randomized-withdrawal Period | Lost to Follow-up | 0 | 13 | 6 |
| Randomized-withdrawal Period | Other | 0 | 9 | 5 |
| Randomized-withdrawal Period | Pregnancy | 0 | 0 | 2 |
| Randomized-withdrawal Period | Protocol Violation | 0 | 1 | 2 |
| Randomized-withdrawal Period | Relapse Criteria Met | 0 | 40 | 5 |
| Randomized-withdrawal Period | Withdrawal by Subject | 0 | 25 | 9 |
Baseline characteristics
| Characteristic | Open-label Safety Population |
|---|---|
| Age, Continuous | 38.3 years STANDARD_DEVIATION 10.4 |
| Age, Customized < 40 years of age | 217 Participants |
| Age, Customized >/= 40 years of age | 194 Participants |
| Sex: Female, Male Female | 358 Participants |
| Sex: Female, Male Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 303 / 411 | 45 / 134 | 59 / 136 |
| serious Total, serious adverse events | 3 / 411 | 0 / 134 | 2 / 136 |
Outcome results
Primary
Time to Relapse From Date of Randomization to Endpoint of The Randomized-withdrawal Period
Relapse status was assessed during the double-blind treatment phase and was defined as having 2 or more binge days per week for 2 consecutive weeks (14 consecutive days) prior to any visit and having an increase in Clinical Global Impressions-Severity (CGI-S) score of 2 or more points compared to the randomized-withdrawal baseline (date of relapse - date of randomization). Binge eating information was captured via a self-report paper diary. The binge diary captured the number of binges per day, total hours per day spent binging, type of binge (at mealtime or at another time other than mealtime), and a description of the binge (amounts and types of foods). Binge frequency was reviewed by the clinician with the subject to confirm reported binge episodes per day. The CGI-S was performed to rate the severity of a subject's condition using a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill).
Time frame: Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Population: The Full Analysis Set (FAS): participants in the Randomized Safety Analysis Set (RSAS) with at least 1 post-randomization CGI-S assessment. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Randomized-withdrawal Period) | Time to Relapse From Date of Randomization to Endpoint of The Randomized-withdrawal Period | NA days |
| SPD489 (Randomized-withdrawal Period) | Time to Relapse From Date of Randomization to Endpoint of The Randomized-withdrawal Period | NA days |
p-value: <0.001Log Rank
Secondary
Change From Randomized-Withdrawal Baseline in The Number of Binge- Eating Days Per Week During The Randomized-withdrawal Period
A binge day was defined as days during which at least 1 binge episode occurred. As assessed by clinical interview based on subject binge diary. Binge eating information was captured via a self-report paper diary. The binge diary captured the number of binges per day, total hours per day spent binging, type of binge (at mealtime or at another time other than mealtime), and a description of the binge (amounts and types of foods). Binge frequency was reviewed by the clinician with the subject to confirm reported binge episodes per day. A negative change from Baseline indicates that binge-related behavior decreased. The randomized -withdrawal-baseline was defined as the weekly average number of binge days for the 14 days prior to the Randomization Visit (Visit 8).
Time frame: Randomized--withdrawal baseline (Visit 8; 12 weeks after start of open- label treatment [Week 12]), Visit 21 (26 weeks after randomization [Week 38])
Population: The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 included only participants who completed randomized treatment (placebo: n=50; SPD489: n=102).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Change From Randomized-Withdrawal Baseline in The Number of Binge- Eating Days Per Week During The Randomized-withdrawal Period | 0.63 days | Standard Error 0.076 |
| SPD489 (Randomized-withdrawal Period) | Change From Randomized-Withdrawal Baseline in The Number of Binge- Eating Days Per Week During The Randomized-withdrawal Period | 0.02 days | Standard Error 0.061 |
p-value: <0.00195% CI: [-0.81, -0.42]mixed- effects model for repeated measur
Secondary
Change From Randomized-Withdrawal Baseline in The Total Score of The Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) During The Randomized-withdrawal Period
The Y-BOCS-BE measures the obsession of binge eating thoughts and compulsiveness of binge eating behaviors. The scale is a clinician rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms). The scale includes questions regarding the amount of time spent on obsessions, impairment or distress experienced, and resistance and control over these thoughts. The same types of questions were asked about compulsions (ie, time spent, interference, etc.).Total scores range from 0 to 40. A total score of 0-7 is sub-clinical, 8-15 is mild, 16-23 is moderate, 24-31 is severe, and 32-40 is extreme. A decrease from baseline in Y-BOCS-BE Total Score represents an improvement in obsession with binge-eating thoughts or compulsiveness of binge-eating behaviors.
Time frame: Randomized-withdrawal baseline (Visit 8; 12 weeks after start of open-label treatment [Week 12]), Visit 21 (26 weeks after randomization [Week 38])
Population: The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 included only participants who completed randomized treatment (placebo: n=54; SPD489: n=107).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Change From Randomized-Withdrawal Baseline in The Total Score of The Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) During The Randomized-withdrawal Period | 5.5 units on a scale | Standard Error 0.66 |
| SPD489 (Randomized-withdrawal Period) | Change From Randomized-Withdrawal Baseline in The Total Score of The Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) During The Randomized-withdrawal Period | -0.0 units on a scale | Standard Error 0.52 |
p-value: <0.00195% CI: [-7.2, -3.9]mixed-effects model for repeated measure
Secondary
Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Open-label Period
The C-SSRS is a semistructured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answer to the first 2 ideation questions was yes, the clinician asked questions 3-5. Active suicidal ideation included any participant who answered yes to questions 2-5. If the answers to ideation questions 1 and 2 were No, then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide.
Time frame: Visit 8 (12 weeks after start of open-label treatment [Week 12])
Population: The OSP. Three participants in the OSP did not have data collected for this outcome. Visit 8 included only participants who completed open-label treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Open-label Period | Active Suicidal Ideation | 0 participants |
| Placebo (Randomized-withdrawal Period) | Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Open-label Period | Suicidal Behavior | 0 participants |
| Placebo (Randomized-withdrawal Period) | Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Open-label Period | Non-Suicidal Self-Injurious Behavior | 2 participants |
Secondary
Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Randomized-withdrawal Period
The C-SSRS is a semistructured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answer to the first 2 ideation questions was yes, the clinician asked questions 3-5. Active suicidal ideation included any participant who answered yes to questions 2-5. If the answers to ideation questions 1 and 2 were No, then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide.
Time frame: Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Population: The Randomized Safety Analysis Set (RSAS), defined as participants in the SAS who were randomized and took at least 1 dose of investigational product in the randomized-withdrawal period. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS. Three participants had no data for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Randomized-withdrawal Period | Suicidal Behavior | 0 participants |
| Placebo (Randomized-withdrawal Period) | Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Randomized-withdrawal Period | Active Suicidal Ideation | 0 participants |
| Placebo (Randomized-withdrawal Period) | Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Randomized-withdrawal Period | Non-Suicidal Self-Injurious Behavior | 0 participants |
| SPD489 (Randomized-withdrawal Period) | Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Randomized-withdrawal Period | Non-Suicidal Self-Injurious Behavior | 1 participants |
| SPD489 (Randomized-withdrawal Period) | Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Randomized-withdrawal Period | Suicidal Behavior | 0 participants |
| SPD489 (Randomized-withdrawal Period) | Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Randomized-withdrawal Period | Active Suicidal Ideation | 0 participants |
Secondary
Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period
The CGI-S permits a global evaluation of a subject's condition and severity of symptoms. The CGI-S was performed to rate the severity of a subject's condition based on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill).
Time frame: Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Population: The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Mildly Ill | 14.5 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Markedly Ill | 6.9 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Borderline Mentally Ill | 10.7 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Severely Ill | 0.0 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Moderately Ill | 22.1 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Among the Most Extremely Ill | 0.8 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Normal, Not at All Ill | 45.0 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Among the Most Extremely Ill | 0.0 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Normal, Not at All Ill | 81.6 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Borderline Mentally Ill | 11.8 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Mildly Ill | 2.2 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Moderately Ill | 2.2 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Markedly Ill | 2.2 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period | Severely Ill | 0.0 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Open-label Period
The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time frame: Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Population: The OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Open-label Period | I am not anxious or depressed | 80.9 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Open-label Period | I am slightly anxious or depressed | 15.6 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Open-label Period | I am severely anxious or depressed | 1.0 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Open-label Period | Moderately anxious or depressed | 2.3 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Open-label Period | I am extremely anxious or depressed | 0.3 percentage of participants |
Secondary
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period
The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time frame: Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Population: The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | I am slightly anxious or depressed | 26.7 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | I am severely anxious or depressed | 2.6 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | Moderately anxious or depressed | 4.3 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | I am extremely anxious or depressed | 0.0 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | I am not anxious or depressed | 66.4 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | I am extremely anxious or depressed | 0.8 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | I am not anxious or depressed | 79.5 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | I am slightly anxious or depressed | 15.7 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | Moderately anxious or depressed | 3.1 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period | I am severely anxious or depressed | 0.8 percentage of participants |
Secondary
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Mobility at Endpoint of The Open-label Period
The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time frame: Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Population: The Open-label Safety Population (OSP), defined as participants who had taken at least 1 dose of SPD489 in the open-label period and who had a post-baseline safety assessment. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Mobility at Endpoint of The Open-label Period | Moderate problems in walking about | 1.5 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Mobility at Endpoint of The Open-label Period | I have no problems in walking about | 87.9 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Mobility at Endpoint of The Open-label Period | I have slight problems in walking about | 9.8 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Mobility at Endpoint of The Open-label Period | I have severe problems in walking about | 0.8 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Mobility at Endpoint of The Open-label Period | I am unable to walk about | 0 percentage of participants |
Secondary
Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period
The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time frame: Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Population: The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | Moderate problems in walking about | 1.7 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | I have slight problems in walking about | 14.7 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | I have severe problems in walking about | 0.0 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | I am unable to walk about | 0.0 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | I have no problems in walking about | 83.6 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | I am unable to walk about | 0.0 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | I have no problems in walking about | 91.3 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | I have slight problems in walking about | 6.3 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | Moderate problems in walking about | 1.6 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period | I have severe problems in walking about | 0.8 percentage of participants |
Secondary
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Open-label Period
The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time frame: Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Population: The OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Open-label Period | I have no pain or discomfort | 72.3 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Open-label Period | I have extreme pain or discomfort | 0.3 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Open-label Period | I have slight pain or discomfort | 20.9 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Open-label Period | Moderate pain or discomfort | 5.3 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Open-label Period | I have severe pain or discomfort | 1.3 percentage of participants |
Secondary
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period
The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time frame: Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Population: The FAS. Three participants in the placebo group were randomized and included in the RSAS but not included in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | Moderate pain or discomfort | 8.6 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | I have no pain or discomfort | 75.0 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | I have severe pain or discomfort | 0.0 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | I have slight pain or discomfort | 16.4 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | I have extreme pain or discomfort | 0.0 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | I have extreme pain or discomfort | 1.6 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | I have slight pain or discomfort | 18.1 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | Moderate pain or discomfort | 8.7 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | I have severe pain or discomfort | 0.0 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period | I have no pain or discomfort | 71.7 percentage of participants |
Secondary
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Open-label Period
The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time frame: Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Population: The OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Open-label Period | I have no problems washing or dressing myself | 98.7 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Open-label Period | I have slight problems washing or dressing myself | 0.8 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Open-label Period | Moderate problems washing or dressing myself | 0.3 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Open-label Period | I have severe problems washing or dressing myself | 0.3 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Open-label Period | I am unable to wash or dress myself | 0 percentage of participants |
Secondary
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period
The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time frame: Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Population: The FAS. Three participants in the placebo group were randomized and included in the RSAS but not included in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | I am unable to wash or dress myself | 0.0 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | I have no problems washing or dressing myself | 98.3 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | I have slight problems washing or dressing myself | 0.9 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | Moderate problems washing or dressing myself | 0.9 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | I have severe problems washing or dressing myself | 0.0 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | I have severe problems washing or dressing myself | 0.0 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | Moderate problems washing or dressing myself | 0.8 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | I have no problems washing or dressing myself | 98.4 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | I am unable to wash or dress myself | 0.0 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period | I have slight problems washing or dressing myself | 0.8 percentage of participants |
Secondary
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Open-label Period
The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time frame: Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Population: The OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Open-label Period | I have no problems doing my usual activities | 88.9 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Open-label Period | I have slight problems doing my usual activities | 8.1 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Open-label Period | Moderate problems doing my usual activities | 2.3 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Open-label Period | I have severe problems doing my usual activities | 0.8 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Open-label Period | I am unable to do my usual activities | 0 percentage of participants |
Secondary
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period
The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time frame: Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Population: The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | I have slight problems doing my usual activities | 16.4 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | I have severe problems doing my usual activities | 0.0 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | I have no problems doing my usual activities | 79.3 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | I am unable to do my usual activities | 1.7 percentage of participants |
| Placebo (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | Moderate problems doing my usual activities | 2.6 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | I am unable to do my usual activities | 0.0 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | I have slight problems doing my usual activities | 11.0 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | Moderate problems doing my usual activities | 0.8 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | I have severe problems doing my usual activities | 1.6 percentage of participants |
| SPD489 (Randomized-withdrawal Period) | Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period | I have no problems doing my usual activities | 86.6 percentage of participants |
Secondary
Total Scores For The Amphetamine Cessation Symptom Assessment (ACSA) Scale During Follow-up
The ACSA was used in this study to assess potential withdrawal symptoms associated with chronic use of SPD489. The ACSA is a self-completed scale used to assess withdrawal symptoms. The scale has 16 symptom items rated on a 5-point scale ranging from 0 (not at all) to 4 (extremely). The ACSA total score ranges from 0-64, where a higher score indicates greater withdrawal symptom severity.
Time frame: Visit 21 (26 weeks after randomization [Week 38] or Early Termination) and Visit 22 (7 days post last dose)
Population: The RSAS. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS. Visits 21 and 22 could include participants who discontinued but completed a final safety and efficacy assessment. Not all participants had data for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Randomized-withdrawal Period) | Total Scores For The Amphetamine Cessation Symptom Assessment (ACSA) Scale During Follow-up | Visit 22, n=75, 78 | 4.6 units on a scale | Standard Deviation 5.84 |
| Placebo (Randomized-withdrawal Period) | Total Scores For The Amphetamine Cessation Symptom Assessment (ACSA) Scale During Follow-up | Visit 21, n=88, 94 | 7.6 units on a scale | Standard Deviation 8.33 |
| SPD489 (Randomized-withdrawal Period) | Total Scores For The Amphetamine Cessation Symptom Assessment (ACSA) Scale During Follow-up | Visit 21, n=88, 94 | 4.9 units on a scale | Standard Deviation 7.81 |
| SPD489 (Randomized-withdrawal Period) | Total Scores For The Amphetamine Cessation Symptom Assessment (ACSA) Scale During Follow-up | Visit 22, n=75, 78 | 5.3 units on a scale | Standard Deviation 7.98 |