Evaluate the Maintenance of Efficacy of SPD489 in Adults... | NCT02009163

ID	Type	Description	Link
2012-004457-88	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Lisdexamfetamine dimesylate	Experimental	Administer one capsule (50 or 70 mg) orally daily at approximately 7:00 AM.	Drug: Lisdexamfetamine dimesylate
Placebo	Placebo Comparator	Administer one capsule orally daily at approximately 7:00 AM.	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Lisdexamfetamine dimesylate	Drug	SDP489 30, 50, or 70mg capsule once per day (open-label and double-blind periods)	Lisdexamfetamine dimesylate

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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).	Visit 21 (26 weeks after randomization [Week 38] or Early Termination)

Secondary Outcomes

Measure	Description	Time Frame
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).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject is between 18-55 years of age, inclusive.
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.
Subject is consistently able to swallow a capsule.

Exclusion Criteria:

Subject has current diagnosis of bulimia nervosa or anorexia nervosa.
Subject is receiving psychotherapy or weight loss support within the past 3 months.
Subject has used psychostimulants to facilitate fasting or dieting within the past 6 months.
Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease.
Subject has abnormal thyroid function.
Subject initiated treatment with a lipid lowering medication within the past 3 months.
Subject has a history of moderate or severe hypertension.
Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder.
Subject has glaucoma.
Subject is female and pregnant or nursing.
Subjects who have had bariatric surgery, lap bands, duodenal stents, or other procedures for weight loss.

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Gulfcoast Clinical Research Center		Fort Myers	Florida	33912	United States
Innovative Clinical Research, Inc

PubMed Identifier	Type	Citation	Retractions
32237290	Derived	Robertson B, Wu J, Fant RV, Schnoll SH, McElroy SL. Assessment of Amphetamine Withdrawal Symptoms of Lisdexamfetamine Dimesylate Treatment for Adults With Binge-Eating Disorder. Prim Care Companion CNS Disord. 2020 Mar 26;22(2):19m02540. doi: 10.4088/PCC.19m02540.
28700805	Derived	Hudson JI, McElroy SL, Ferreira-Cornwell MC, Radewonuk J, Gasior M. Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2017 Sep 1;74(9):903-910. doi: 10.1001/jamapsychiatry.2017.1889.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	SPD489 (Open-label Period)	SPD489 treatment was taken orally once daily at approximately 7:00 AM. All participants began treatment with SPD489 at the lowest dose level (30mg) during the 4-week open-label dose-optimization period. After 1 week of treatment at 30mg, all participants were titrated to the next dose level (50mg). After 1 week of treatment at 50mg, all participants were titrated to the highest dose level (70mg), as tolerated and as clinically indicated. After 1 week of treatment at the highest dose, the participant could have been down-titrated to 50mg; no further dose adjustments were permitted. The optimal daily dose of 50 or 70mg achieved during dose-optimization was maintained throughout the 8-week dose-maintenance period. The total time of the open-label period was 12 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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).

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.

Posted

Median

Inter-Quartile Range

days

Visit 21 (26 weeks after randomization [Week 38] or Early Termination)

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
OG001	SPD489 (Randomized-withdrawal Period)	For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.

Units	Counts
Participants	OG000131 OG001136

Title

Denominators

Categories

Title

Measurements

OG000NA(55.0 to NA)As neither treatment group had over 50% of subjects experiencing relapse during the 26-week randomized-withdrawal phase, the median time to relapse and inter-quartile range was not calculable.
OG001NA(NA to NA)As neither treatment group had over 50% of subjects experiencing relapse during the 26-week randomized-withdrawal phase, the median time to relapse and inter-quartile range was not calculable.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		<0.001	P-value based on a log-rank test, stratified by 4-week cessation status (Yes, No). 4-week cessation was defined as a subject having no binge days during the 4 weeks prior to randomization.					2-Sided								Superiority or Other (legacy)

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).

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).

Posted

Least Squares Mean

Standard Error

days

Randomized--withdrawal baseline (Visit 8; 12 weeks after start of open- label treatment [Week 12]), Visit 21 (26 weeks after randomization [Week 38])

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.

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).

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.

Posted

Number

percentage of participants

Visit 21 (26 weeks after randomization [Week 38] or Early Termination)

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
OG001	SPD489 (Randomized-withdrawal Period)	For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.

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.

Posted

Least Squares Mean

Standard Error

units on a scale

Randomized-withdrawal baseline (Visit 8; 12 weeks after start of open-label treatment [Week 12]), Visit 21 (26 weeks after randomization [Week 38])

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.

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.

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.

Posted

Number

percentage of participants

Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)

ID	Title	Description
OG000	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.

Units	Counts

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 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.

Posted

Number

percentage of participants

Visit 21 (26 weeks after randomization [Week 38] or Early Termination)

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
OG001	SPD489 (Randomized-withdrawal Period)

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 OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.

Posted

Number

percentage of participants

Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)

ID	Title	Description
OG000	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.

Units	Counts
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 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.

Posted

Number

percentage of participants

Visit 21 (26 weeks after randomization [Week 38] or Early Termination)

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
OG001	SPD489 (Randomized-withdrawal Period)

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 OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.

Posted

Number

percentage of participants

Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)

ID	Title	Description
OG000	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.

Units	Counts
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 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.

Posted

Number

percentage of participants

Visit 21 (26 weeks after randomization [Week 38] or Early Termination)

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
OG001	SPD489 (Randomized-withdrawal Period)

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 OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.

Posted

Number

percentage of participants

Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)

ID	Title	Description
OG000	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.

Units	Counts
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

Posted

Number

percentage of participants

Visit 21 (26 weeks after randomization [Week 38] or Early Termination)

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
OG001	SPD489 (Randomized-withdrawal Period)

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 OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.

Posted

Number

percentage of participants

Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)

ID	Title	Description
OG000	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.

Units	Counts
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 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.

Posted

Number

percentage of participants

Visit 21 (26 weeks after randomization [Week 38] or Early Termination)

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
OG001	SPD489 (Randomized-withdrawal Period)

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.

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.

Posted

Number

participants

Visit 8 (12 weeks after start of open-label treatment [Week 12])

ID	Title	Description
OG000	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 phase and who had a post-baseline safety assessment.

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 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.

Posted

Number

participants

Visit 21 (26 weeks after randomization [Week 38] or Early Termination)

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.

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.

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.

Posted

Mean

Standard Deviation

units on a scale

Visit 21 (26 weeks after randomization [Week 38] or Early Termination) and Visit 22 (7 days post last dose)

ID	Title	Description
OG000	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
OG001	SPD489 (Randomized-withdrawal Period)	For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	SPD489 (Open-label Period)	SPD489 treatment was taken orally once daily at approximately 7:00 AM. All participants began treatment with SPD489 at the lowest dose level (30mg) during the 4-week open-label dose-optimization period. After 1 week of treatment at 30mg, all participants were titrated to the next dose level (50mg). After 1 week of treatment at 50mg, all participants were titrated to the highest dose level (70mg), as tolerated and as clinically indicated. After 1 week of treatment at the highest dose, the participant could have been down-titrated to 50mg; no further dose adjustments were permitted. The optimal daily dose of 50 or 70mg achieved during dose-optimization was maintained throughout the 8-week dose-maintenance period. The total time of the open-label period was 12 weeks.	3	411	303	411
EG001	Placebo (Randomized-withdrawal Period)	During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week .	0	134	45	134
EG002	SPD489 (Randomized-withdrawal Period)	For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.	2	136	59	136

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dry mouth	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG000145 events139 affected411 at risk EG0012 events2 affected134 at risk EG0027 events7 affected136 at risk
Headache	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG00084 events66 affected411 at risk EG0019 events9 affected134 at risk EG00214 events12 affected136 at risk
Insomnia	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG00046 events46 affected411 at risk EG0012 events2 affected134 at risk EG0021 events1 affected136 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG00044 events38 affected411 at risk EG0010 events0 affected134 at risk EG0020 events0 affected136 at risk
Nausea	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG00037 events35 affected411 at risk EG0013 events3 affected134 at risk EG0026 events6 affected136 at risk
Anxiety	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG00032 events29 affected411 at risk EG0012 events2 affected134 at risk EG0022 events2 affected136 at risk
Constipation	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG00029 events28 affected411 at risk EG0011 events1 affected134 at risk EG0024 events4 affected136 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG00024 events23 affected411 at risk EG0010 events0 affected134 at risk EG0023 events3 affected136 at risk
Feeling jittery	General disorders	MedDRA 16.1	Systematic Assessment	EG00026 events21 affected411 at risk EG0010 events0 affected134 at risk EG0020 events0 affected136 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG00024 events21 affected411 at risk EG0013 events3 affected134 at risk EG0022 events2 affected136 at risk
Nasopharyngitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG00020 events20 affected411 at risk EG0019 events9 affected134 at risk EG00215 events13 affected136 at risk
Irritability	General disorders	MedDRA 16.1	Systematic Assessment	EG00022 events19 affected411 at risk EG0015 events4 affected134 at risk EG0024 events4 affected136 at risk
Fatigue	General disorders	MedDRA 16.1	Systematic Assessment	EG00019 events18 affected411 at risk EG0017 events7 affected134 at risk EG0024 events4 affected136 at risk
Tachycardia	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG00020 events17 affected411 at risk EG0010 events0 affected134 at risk EG0023 events2 affected136 at risk
Blood pressure increased	Investigations	MedDRA 16.1	Systematic Assessment	EG00017 events15 affected411 at risk EG0010 events0 affected134 at risk EG0021 events1 affected136 at risk
Heart rate increased	Investigations	MedDRA 16.1	Systematic Assessment	EG00016 events14 affected411 at risk EG0010 events0 affected134 at risk EG0021 events1 affected136 at risk
Weight decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG00014 events14 affected411 at risk EG0011 events1 affected134 at risk EG0021 events1 affected136 at risk
Palpitations	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG00013 events13 affected411 at risk EG0010 events0 affected134 at risk EG0021 events1 affected136 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG00011 events11 affected411 at risk EG0017 events5 affected134 at risk EG00212 events11 affected136 at risk
Dizziness	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG00011 events10 affected411 at risk EG0010 events0 affected134 at risk EG0024 events1 affected136 at risk
Thirst	General disorders	MedDRA 16.1	Systematic Assessment	EG00011 events9 affected411 at risk EG0010 events0 affected134 at risk EG0020 events0 affected136 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG00010 events9 affected411 at risk EG0011 events1 affected134 at risk EG0022 events2 affected136 at risk
Somnolence	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected411 at risk EG0013 events3 affected134 at risk EG0025 events5 affected136 at risk
Urinary tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0007 events7 affected411 at risk EG0014 events4 affected134 at risk EG0024 events4 affected136 at risk
Initial insomnia	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0007 events6 affected411 at risk EG0013 events2 affected134 at risk EG0024 events4 affected136 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0005 events4 affected411 at risk EG0010 events0 affected134 at risk EG0024 events4 affected136 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0006 events5 affected411 at risk EG0012 events2 affected134 at risk EG0023 events3 affected136 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0008 events7 affected411 at risk EG0011 events1 affected134 at risk EG0023 events3 affected136 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0003 events3 affected411 at risk EG0011 events1 affected134 at risk EG0023 events3 affected136 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0002 events2 affected411 at risk EG0010 events0 affected134 at risk EG0023 events3 affected136 at risk
Bronchitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0005 events5 affected411 at risk EG0010 events0 affected134 at risk EG0023 events3 affected136 at risk
Rhinitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected411 at risk EG0010 events0 affected134 at risk EG0023 events3 affected136 at risk
Gastroenteritis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0005 events5 affected411 at risk EG0013 events3 affected134 at risk EG0022 events2 affected136 at risk
Weight increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected411 at risk EG0011 events1 affected134 at risk EG0023 events3 affected136 at risk

ID	Term
D001068	Feeding and Eating Disorders
D001523	Mental Disorders

ID	Term
D003913	Dextroamphetamine
D000661	Amphetamine
D000662	Amphetamines
D010627	Phenethylamines
D005021	Ethylamines
D000588	Amines
D009930	Organic Chemicals

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Congenital Anomaly in Offspring	Congenital, familial and genetic disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected411 at risk EG0010 events0 affected134 at risk EG0020 events0 affected136 at risk
Pneumonia	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected411 at risk EG0010 events0 affected134 at risk EG0020 events0 affected136 at risk
Convulsion	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected411 at risk EG0010 events0 affected134 at risk EG0020 events0 affected136 at risk
Nerve Root Compression	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected411 at risk EG0010 events0 affected134 at risk EG0021 events1 affected136 at risk
Breast Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected411 at risk EG0010 events0 affected134 at risk EG0021 events1 affected136 at risk