Trial Outcomes & Findings for Evaluate the Maintenance of Efficacy of SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder (NCT NCT02009163)

NCT ID: NCT02009163

Last Updated: 2021-06-14

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

418 participants

Primary outcome timeframe

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

Results posted on

2021-06-14

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.	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.
Open-label Period (Non-randomized) STARTED	418	0	0
Open-label Period (Non-randomized) COMPLETED	275	0	0
Open-label Period (Non-randomized) NOT COMPLETED	143	0	0
Randomized-withdrawal Period STARTED	0	138	137
Randomized-withdrawal Period COMPLETED	0	50	102
Randomized-withdrawal Period NOT COMPLETED	0	88	35

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Open-label Period (Non-randomized) Failure to Meet Randomization Criteria	48	0	0
Open-label Period (Non-randomized) Withdrawal by Subject	29	0	0
Open-label Period (Non-randomized) Adverse Event	22	0	0
Open-label Period (Non-randomized) Lost to Follow-up	20	0	0
Open-label Period (Non-randomized) Protocol Violation	10	0	0
Open-label Period (Non-randomized) Pregnancy	1	0	0
Open-label Period (Non-randomized) Other	13	0	0
Randomized-withdrawal Period Withdrawal by Subject	0	25	9
Randomized-withdrawal Period Lost to Follow-up	0	13	6
Randomized-withdrawal Period Adverse Event	0	0	6
Randomized-withdrawal Period Relapse Criteria Met	0	40	5
Randomized-withdrawal Period Protocol Violation	0	1	2
Randomized-withdrawal Period Pregnancy	0	0	2
Randomized-withdrawal Period Other	0	9	5

Baseline Characteristics

Evaluate the Maintenance of Efficacy of SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-label Safety Population n=411 Participants 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.
Age, Continuous	38.3 years STANDARD_DEVIATION 10.40 • n=5 Participants
Age, Customized < 40 years of age	217 Participants n=5 Participants
Age, Customized >/= 40 years of age	194 Participants n=5 Participants
Sex: Female, Male Female	358 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=131 Participants 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.	SPD489 (Randomized-withdrawal Period) n=136 Participants 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.
Time to Relapse From Date of Randomization to Endpoint of The Randomized-withdrawal Period	NA days Interval 55.0 to 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.	NA days 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.

SECONDARY outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=131 Participants 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.	SPD489 (Randomized-withdrawal Period) n=136 Participants 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.
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	0.02 days Standard Error 0.061

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=131 Participants 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.	SPD489 (Randomized-withdrawal Period) n=136 Participants 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.
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	81.6 percentage of participants
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	11.8 percentage of participants
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	2.2 percentage of participants
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	2.2 percentage of participants
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	2.2 percentage of participants
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	0.0 percentage of participants
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	0.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=131 Participants 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.	SPD489 (Randomized-withdrawal Period) n=136 Participants 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.
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	-0.0 units on a scale Standard Error 0.52

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=397 Participants 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.	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.
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	—
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	—
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	—
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	—
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=116 Participants 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.	SPD489 (Randomized-withdrawal Period) n=127 Participants 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.
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	91.3 percentage of participants
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	6.3 percentage of participants
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	1.6 percentage of participants
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	0.8 percentage of participants
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	0.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=397 Participants 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.	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.
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	—
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	—
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	—
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	—
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=116 Participants 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.	SPD489 (Randomized-withdrawal Period) n=127 Participants 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.
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	98.4 percentage of participants
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	0.8 percentage of participants
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	0.8 percentage of participants
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	0.0 percentage of participants
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	0.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=397 Participants 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.	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.
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	—
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	—
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	—
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	—
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=116 Participants 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.	SPD489 (Randomized-withdrawal Period) n=127 Participants 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.
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	86.6 percentage of participants
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	11.0 percentage of participants
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	0.8 percentage of participants
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	1.6 percentage of participants
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	0.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=397 Participants 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.	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.
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	—
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	—
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	—
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	—
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	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=116 Participants 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.	SPD489 (Randomized-withdrawal Period) n=127 Participants 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.
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	71.7 percentage of participants
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	18.1 percentage of participants
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	8.7 percentage of participants
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	0.0 percentage of participants
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	1.6 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=397 Participants 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.	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.
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	—
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	—
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	—
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	—
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=116 Participants 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.	SPD489 (Randomized-withdrawal Period) n=127 Participants 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.
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	79.5 percentage of participants
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	15.7 percentage of participants
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	3.1 percentage of participants
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	0.8 percentage of participants
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	0.8 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=408 Participants 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.	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.
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	—
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	—
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=131 Participants 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.	SPD489 (Randomized-withdrawal Period) n=136 Participants 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.
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	0 participants
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	0 participants
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	1 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Randomized-withdrawal Period) n=134 Participants 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.	SPD489 (Randomized-withdrawal Period) n=136 Participants 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.
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	4.9 units on a scale Standard Deviation 7.81
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	5.3 units on a scale Standard Deviation 7.98

Adverse Events

SPD489 (Open-label Period)

Serious events: 3 serious events

Other events: 303 other events

Deaths: 0 deaths

Placebo (Randomized-withdrawal Period)

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

SPD489 (Randomized-withdrawal Period)

Serious events: 2 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SPD489 (Open-label Period) n=411 participants at risk 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.	Placebo (Randomized-withdrawal Period) n=134 participants at risk 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 .	SPD489 (Randomized-withdrawal Period) n=136 participants at risk 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.
Congenital, familial and genetic disorders Congenital Anomaly in Offspring	0.24% 1/411 • Number of events 1 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.	0.00% 0/134 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.	0.00% 0/136 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.
Infections and infestations Pneumonia	0.24% 1/411 • Number of events 1 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.	0.00% 0/134 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.	0.00% 0/136 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.
Nervous system disorders Convulsion	0.24% 1/411 • Number of events 1 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.	0.00% 0/134 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.	0.00% 0/136 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.
Nervous system disorders Nerve Root Compression	0.00% 0/411 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.	0.00% 0/134 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.	0.74% 1/136 • Number of events 1 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/411 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.	0.00% 0/134 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.	0.74% 1/136 • Number of events 1 Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER