Trial Outcomes & Findings for SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder (NCT NCT01718483)

NCT ID: NCT01718483

Last Updated: 2021-06-08

Results Overview

Binge days defined as days during which at least 1 binge episode occurred. As assessed by clinical interview based on participant binge diary.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 383 participants
• Primary outcome timeframe: Baseline and Visit 8 (Weeks 11-12)
• Results posted on: 2021-06-08

Participant Flow

Participants were recruited between 12-Nov-2012 and 19-June-2013 and locations included medical clinics & research centers.

Participant milestones

Measure	PLACEBO Placebo matching SPD489 capsule administered orally, once-daily, for up to 12 weeks.	SPD489 SPD489 capsule 30 (titration purpose only), 50 or 70 milligram (mg) administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Overall Study STARTED	191	192
Overall Study Treated	187	192
Overall Study COMPLETED	157	158
Overall Study NOT COMPLETED	34	34

Reasons for withdrawal

Measure	PLACEBO Placebo matching SPD489 capsule administered orally, once-daily, for up to 12 weeks.	SPD489 SPD489 capsule 30 (titration purpose only), 50 or 70 milligram (mg) administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Overall Study Withdrawal by Subject	14	12
Overall Study Adverse Event	5	12
Overall Study Lost to Follow-up	8	3
Overall Study Protocol Violation	4	2
Overall Study Other	1	4
Overall Study Pregnancy	1	1
Overall Study Lack of Efficacy	1	0

Baseline Characteristics

SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder

Baseline characteristics by cohort

Measure	PLACEBO n=187 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=192 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.	Total n=379 Participants Total of all reporting groups
Age, Continuous	37.6 Years STANDARD_DEVIATION 10.21 • n=5 Participants	38.5 Years STANDARD_DEVIATION 10.4 • n=7 Participants	38.1 Years STANDARD_DEVIATION 10.3 • n=5 Participants
Age, Customized <40 years	102 Participants n=5 Participants	98 Participants n=7 Participants	200 Participants n=5 Participants
Age, Customized >=40 years	85 Participants n=5 Participants	94 Participants n=7 Participants	179 Participants n=5 Participants
Sex: Female, Male Female	163 Participants n=5 Participants	165 Participants n=7 Participants	328 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	27 Participants n=7 Participants	51 Participants n=5 Participants
Region of Enrollment GERMANY	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment SPAIN	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment SWEDEN	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Region of Enrollment UNITED STATES	165 Participants n=5 Participants	173 Participants n=7 Participants	338 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Visit 8 (Weeks 11-12)

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week).

Binge days defined as days during which at least 1 binge episode occurred. As assessed by clinical interview based on participant binge diary.

Outcome measures

Measure	PLACEBO n=184 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=190 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Change From Baseline in the Number of Binge Days Per Week at Visit 8 (Weeks 11-12)	-2.51 Binge days per week Standard Error 0.125	-3.87 Binge days per week Standard Error 0.124

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week).

CGI-I consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.

Outcome measures

Measure	PLACEBO n=184 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=190 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores	47.3 percentage of participants Interval 40.1 to 54.5	82.1 percentage of participants Interval 76.7 to 87.6

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week).

4-week cessation from binge eating is defined as no binge eating episodes for 28 consecutive days prior to the last study visit.

Outcome measures

Measure	PLACEBO n=184 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=190 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Percentage of Participants With a 4-Week Cessation From Binge Eating	14.1 percentage of participants Interval 9.1 to 19.2	40.0 percentage of participants Interval 33.0 to 47.0

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week).

Outcome measures

Measure	PLACEBO n=184 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=190 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Percent Change From Baseline in Body Weight at Week 12	0.11 percent change Standard Error 0.295	-6.25 percent change Standard Error 0.292

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

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). Total scores range from 0 to 40. Reduction in total score indicates improvement.

Outcome measures

Measure	PLACEBO n=183 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=188 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Change From Baseline in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) Total Score at Week 12	-8.28 units on a scale Standard Error 0.550	-15.68 units on a scale Standard Error 0.546

SECONDARY outcome

Timeframe: Baseline and Week 12/Early termination (ET)

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

Outcome measures

Measure	PLACEBO n=183 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=190 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Change From Baseline in Fasting Triglyceride Levels at Up to 12 Weeks	0.122 millimole per liter (mmol/L) Standard Error 0.0405	-0.077 millimole per liter (mmol/L) Standard Error 0.0393

SECONDARY outcome

Timeframe: Baseline and Week 12/ET

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

Outcome measures

Measure	PLACEBO n=183 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=190 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Change From Baseline In Fasting Total Cholesterol Levels at Up to 12 Weeks	-0.094 mmol/L Standard Error 0.0435	-0.305 mmol/L Standard Error 0.0422

SECONDARY outcome

Timeframe: Baseline and Week 12/ET

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

Outcome measures

Measure	PLACEBO n=181 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=189 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Change From Baseline in Hemoglobin A1c Levels at Up to 12 Weeks	0.01 Percent hemoglobin Standard Error 0.016	-0.02 Percent hemoglobin Standard Error 0.015

SECONDARY outcome

Timeframe: Week 12/ET

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

Response is based on the reduction in the number of binge eating episodes. Percentage of participants with response was reported. Responses were categorized as follows: 1-week Cessation = 100% reduction in binge episodes during the preceding 7 days. Marked Reduction = 99% to 75% reduction during the time since the previous visit. Moderate Reduction = 74% to 50% reduction during the time since the previous visit. Negative to Minimal Reduction = <50% reduction during the time since the previous visit.

Outcome measures

Measure	PLACEBO n=184 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=187 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Binge Eating Response 1-week cessation	26.6 percentage of participants	47.1 percentage of participants
Binge Eating Response Marked Reduction	15.2 percentage of participants	31.6 percentage of participants
Binge Eating Response Moderate Reduction	17.9 percentage of participants	11.8 percentage of participants
Binge Eating Response Negative to Minimal Reduction	40.2 percentage of participants	9.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Visit 8 (Weeks 11-12)

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week).

Outcome measures

Measure	PLACEBO n=184 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=190 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Change From Baseline in the Number of Binge Episodes Per Week at Visit 8 (Weeks 11-12)	-3.49 Binge episodes per week Standard Error 0.170	-5.27 Binge episodes per week Standard Error 0.168

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

The Eating Inventory also known as the Three-Factor Eating Questionnaire is a 51-item self-reported questionnaire intended to assess 3 dimensions of eating behavior. There are 36 true/false items, 14 items on a 4-point Likert scale (1=eat rarely to 4=always), and 1 item on a 6-point Likert scale (1=eat whatever you want to 6=constantly limiting food intake). Cognitive Restraint score ranges from 0-21. Hunger score ranges from 0-14. Disinhibition score ranges from 0-16. Higher scores denote higher levels of restrained eating, disinhibited eating and predisposition to hunger.

Outcome measures

Measure	PLACEBO n=184 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=188 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Change From Baseline in Eating Inventory Scores at Week 12 Disinhibition of Eating	-2.12 units on a scale Standard Error 0.286	-6.31 units on a scale Standard Error 0.285
Change From Baseline in Eating Inventory Scores at Week 12 Perceived Hunger	-1.90 units on a scale Standard Error 0.286	-6.60 units on a scale Standard Error 0.285
Change From Baseline in Eating Inventory Scores at Week 12 Cognitive Restraint of Eating	1.63 units on a scale Standard Error 0.331	3.27 units on a scale Standard Error 0.329

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

The BES is a self-reported questionnaire containing 16 items designed to assess behavioral, affective, and attitudinal components of the subjective experience of binge eating. Each item is assessed based on 1 of 4 responses, with 1 denoting that a participant has greater control over eating behavior and 4 denoting that a participant had less control over eating behavior. A total score (sum of the 16 items) may range from 16-64. A lower score indicates greater control over eating behavior.

Outcome measures

Measure	PLACEBO n=184 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=189 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Change From Baseline in Binge Eating Scale (BES) Score at Week 12	-8.55 units on a scale Standard Error 0.763	-18.87 units on a scale Standard Error 0.755

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

The FrSBe is a 46-item self-rating scale designed to measure the neurobehavioral traits associated with the 3 primary regions of the prefrontal cortex. Participants were asked to indicate the frequency with which they have engaged in certain behaviors using a rating scale from "1" (almost never) to "5" (almost always). Summary scores were calculated and converted to t-score. A decrease from baseline in FrSBe total score represents improvement.

Outcome measures

Measure	PLACEBO n=182 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=187 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Change From Baseline in Frontal Systems Behavior (FrSBe) Total Score at Week 12	-3.09 t-scores Standard Error 0.592	-3.40 t-scores Standard Error 0.572

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. 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. Percentage of participants with various mobility conditions were reported.

Outcome measures

Measure	PLACEBO n=178 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=187 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Mobility No problems walking about	82.6 percentage of participants	87.2 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Mobility Slight problems walking about	14.0 percentage of participants	10.7 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Mobility Moderate problems walking about	2.8 percentage of participants	2.1 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Mobility Severe problems walking about	0.6 percentage of participants	0 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Mobility Unable to walk about	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. 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. Percentage of participants with various self-care conditions were reported.

Outcome measures

Measure	PLACEBO n=178 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=187 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Self-Care No problems washing or dressing	89.3 percentage of participants	95.7 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Self-Care Slight problems washing or dressing	6.7 percentage of participants	3.2 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Self-Care Moderate problems washing or dressing	3.9 percentage of participants	1.1 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Self-Care Severe problems washing or dressing	0 percentage of participants	0 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Self-Care Unable to wash or dress	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. 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. Percentage of participants with various usual activities conditions were reported.

Outcome measures

Measure	PLACEBO n=177 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=186 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Usual Activities No problems doing usual activities	78.0 percentage of participants	87.1 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Usual Activities Slight problems doing usual activities	14.7 percentage of participants	9.7 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Usual Activities Moderate problems doing usual activities	6.2 percentage of participants	3.2 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Usual Activities Severe problems doing usual activities	1.1 percentage of participants	0 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Usual Activities Unable to do usual activities	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. 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. Percentage of participants with various pain/discomfort conditions were reported.

Outcome measures

Measure	PLACEBO n=178 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=187 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Pain/Discomfort Moderate pain or discomfort	7.3 percentage of participants	7.5 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Pain/Discomfort Severe pain or discomfort	0.6 percentage of participants	0.5 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Pain/Discomfort Extreme pain or discomfort	0 percentage of participants	0 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Pain/Discomfort No pain or discomfort	64.6 percentage of participants	71.1 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Pain/Discomfort Slight pain or discomfort	27.5 percentage of participants	20.9 percentage of participants

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: The Full Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had 1 post-baseline primary efficacy assessment (number of binge days per week calculated for at least 1 week). Not all participants had data for this outcome.

Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. 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. Percentage of participants with various anxiety/depression conditions were reported.

Outcome measures

Measure	PLACEBO n=178 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=187 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Anxiety/Depression Not anxious or depressed	70.2 percentage of participants	72.2 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Anxiety/Depression Slightly anxious or depressed	19.7 percentage of participants	16.6 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Anxiety/Depression Moderately anxious or depressed	7.9 percentage of participants	9.1 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Anxiety/Depression Severely anxious or depressed	2.2 percentage of participants	1.6 percentage of participants
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Anxiety/Depression Extremely anxious or depressed	0 percentage of participants	0.5 percentage of participants

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: The Safety Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had at least 1 post-baseline safety assessment completed. Not all participants had data for this outcome.

C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. 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 assessment is done by the nature of the responses, not by a numbered scale. Number of participants with suicidal ideation and suicidal behavior were reported.

Outcome measures

Measure	PLACEBO n=187 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=191 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal behavior	0 participants	0 participants
Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation	3 participants	2 participants

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: The Safety Analysis Set was defined as all randomized participants who took at least 1 dose of investigational product and who had at least 1 post-baseline safety assessment completed. Not all participants had data for this outcome.

ACSA scale has 16 symptom items rated on a scale from 0 (not at all) to 4 (extremely) with a possible total score range of 0 to 64. Higher scores indicate greater withdrawal symptom severity.

Outcome measures

Measure	PLACEBO n=138 Participants Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=155 Participants SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Amphetamine Cessation Symptom Assessment (ACSA) Total Score	7.3 units on a scale Standard Deviation 7.74	5.7 units on a scale Standard Deviation 7.37

Adverse Events

PLACEBO

Serious events: 2 serious events

Other events: 67 other events

Deaths: 0 deaths

SPD489

Serious events: 3 serious events

Other events: 125 other events

Deaths: 0 deaths

Serious adverse events

Measure	PLACEBO n=187 participants at risk Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=192 participants at risk SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Hepatobiliary disorders Cholecystitis	0.00% 0/187 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	0.52% 1/192 • Number of events 1 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Immune system disorders Anaphylactic reaction	0.53% 1/187 • Number of events 1 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	0.00% 0/192 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Nervous system disorders Syncope	0.00% 0/187 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	1.0% 2/192 • Number of events 2 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Psychiatric disorders Conversion disorder	0.53% 1/187 • Number of events 1 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	0.00% 0/192 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks

Other adverse events

Measure	PLACEBO n=187 participants at risk Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.	SPD489 n=192 participants at risk SPD489 capsule 30 (titration purpose only), 50 or 70 mg administered orally, once-daily for up to 12 weeks once the optimal dose is reached.
Gastrointestinal disorders Constipation	2.1% 4/187 • Number of events 4 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	5.7% 11/192 • Number of events 11 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Gastrointestinal disorders Dry mouth	8.6% 16/187 • Number of events 19 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	39.6% 76/192 • Number of events 86 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Gastrointestinal disorders Nausea	7.5% 14/187 • Number of events 15 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	8.3% 16/192 • Number of events 19 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
General disorders Fatigue	5.3% 10/187 • Number of events 11 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	3.6% 7/192 • Number of events 7 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
General disorders Feeling jittery	1.1% 2/187 • Number of events 3 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	5.7% 11/192 • Number of events 13 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
General disorders Irritability	7.0% 13/187 • Number of events 13 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	8.3% 16/192 • Number of events 18 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Infections and infestations Upper respiratory tract infection	5.9% 11/187 • Number of events 12 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	4.2% 8/192 • Number of events 10 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Investigations Heart rate increased	2.7% 5/187 • Number of events 5 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	7.3% 14/192 • Number of events 14 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Metabolism and nutrition disorders Decreased appetite	3.2% 6/187 • Number of events 6 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	8.9% 17/192 • Number of events 17 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Nervous system disorders Headache	9.1% 17/187 • Number of events 19 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	13.5% 26/192 • Number of events 32 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Psychiatric disorders Anxiety	1.1% 2/187 • Number of events 2 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	6.8% 13/192 • Number of events 13 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Psychiatric disorders Insomnia	7.5% 14/187 • Number of events 15 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	17.7% 34/192 • Number of events 44 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks
Skin and subcutaneous tissue disorders Hyperhidrosis	0.53% 1/187 • Number of events 1 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks	5.2% 10/192 • Number of events 10 • From first dose of study drug up to 3 days after the last dose at up to 12 weeks

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

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