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

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01718509
• Collaborator: (none)
• Enrollment: 390
• Locations: 48
• Arms: 2
• Actual Duration (Months): 9.8
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The primary objective of the study is to demonstrate the efficacy of SPD489 compared with placebo in adults (18 55 years of age inclusive) with moderate to severe Binge Eating Disorder at Visit 8 (Weeks 11 and 12) as measured by the number of binge days (defined as days during which at least 1 binge episode occurs) per week as assessed by clinical interview based on subject diary

Condition or Disease	Intervention/Treatment	Phase
Binge Eating Disorder	Drug: SPD489 (Lisdexamfetamine dimesylate); Drug: Placebo	Phase 3

Detailed Description

Not Required

Study Design

• Study Type: Interventional
• Actual Enrollment: 390 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The SPD489-344, Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Dose-optimization Study to Evaluate the Efficacy, Safety, and Tolerability of SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder
• Actual Study Start Date: Nov 26, 2012
• Actual Primary Completion Date: Sep 20, 2013
• Actual Study Completion Date: Sep 20, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SPD489 (Lisdexamfetamine dimesylate)	Drug: SPD489 (Lisdexamfetamine dimesylate); 50 or 70 mg administered orally, once-daily for up to 12 weeks; Other Names: Vyvanse, Venvanse, LDX
Placebo Comparator: Placebo	Drug: Placebo; Administered once-daily, orally, for up to 12 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Number of Binge Days Per Week at Visit 8 Which Spans Weeks 11/12 [Baseline and Visit 8 Which Spans Weeks 11/12]

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

Secondary Outcome Measures

1. Percent of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores [Up to 12 weeks]

   Clinical Global Impression-Improvement (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.

2. Percent of Participants With a 4-Week Cessation From Binge Eating [Up to 12 weeks]

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

3. Percent Change From Baseline in Body Weight (kg) at Week 12 [Baseline and week 12]

4. Change From Baseline in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) Total Score at Week 12 [Baseline and week 12]

   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.

5. Change From Baseline in Fasting Triglyceride Levels at Up to 12 Weeks [Baseline and up to 12 weeks]

6. Change From Baseline In Fasting Total Cholesterol Levels at Up to 12 Weeks [Baseline and up to 12 weeks]

7. Change From Baseline in Hemoglobin A1c Levels at Up to 12 Weeks [Baseline and up to 12 weeks]

8. Binge Eating Response [Up to 12 weeks]

   Response is based on the reduction in the number of binge eating episodes. 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

9. Change From Baseline in the Number of Binge Episodes Per Week at Visit 8 Which Spans Weeks 11/12 [Baseline and Visit 8 Which Spans Weeks 11/12]

10. Change From Baseline in Eating Inventory Scores at Week 12 [Baseline and week 12]

    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.

11. Change From Baseline in Binge Eating Scale (BES) Score at Week 12 [Baseline and week 12]

    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 subject has greater control over eating behavior and 4 denoting that a subject 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.

12. Change From Baseline in Frontal Systems Behavior (FrSBe) Total Score at Up to 12 Weeks [Baseline and up to 12 weeks]

    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. Subjects 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.

13. EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Mobility [Up to 12 weeks]

    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.

14. EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Self-Care [Up to 12 weeks]

15. EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Usual Activities [Up to 12 weeks]

16. EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Pain/Discomfort [Up to 12 weeks]

17. EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Anxiety/Depression [Up to 12 weeks]

18. Columbia-Suicide Severity Rating Scale (C-SSRS) [Up to 12 weeks]

    C-SSRS is a semi-structured interview that captures the occurence, 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.

19. Change in Amphetamine Cessation Symptom Assessment (ACSA) Total Score From Baseline to Week 12. [Baseline and Week 12]

    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. Calculated as Baseline (Day 0) - Week 12 ACSA scores.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

The subject cannot be enrolled in the study before all of the following inclusion criteria (including test results) are met:

1. Subject is between 18-55 years of age.

2. Subject meets the following Diagnostic and Statistical Manual of Mental Disorders

Fourth Edition - Text Revision (DSM-IV-TR) criteria for a diagnosis of BED:

1. Subject has a BED diagnosis.

2. Subject's BED is of at least moderate severity with subjects reporting at least 3 binge eating days per week.

3. Female subjects must have a negative serum B-HCG pregnancy test and a negative urine pregnancy test and agree to comply with any applicable contraceptive requirements.

Exclusion Criteria:

Subjects are excluded from the study if any of the following exclusion criteria are met:

1. Subject has concurrent symptoms of bulimia nervosa or anorexia nervosa.

2. Subject is receiving psychotherapy (eg, supportive psychotherapy, cognitive behavior therapy, interpersonal therapy) or weight loss support (eg, Weight Watchers) for BED.

3. Subject has used psychostimulants to facilitate fasting or dieting as a part of their BED.

4. Subject has a lifetime history of psychosis, mania, hypomania, dementia, or ADHD.

5. Subject is considered a suicide risk, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation.

6. Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems.

7. Subject has a history of moderate or severe hypertension.

8. Subject is female and pregnant or nursing.

9. Subject has had bariatric surgery, lap bands, duodenal stents, or other procedures for weight loss.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radiant Research, Inc.	Tucson	Arizona	United States	85710
2	Southern California Research, LLC	Beverly Hills	California	United States	90210
3	Scripps Clinical Research Services	La Jolla	California	United States	92037
4	Pharmacology Research Institute	Newport Beach	California	United States	92660
5	Excel Research, Inc.	Oceanside	California	United States	92056
6	PCSD - Feighner Research	San Diego	California	United States	92108
7	Radiant Research, Inc.	Denver	Colorado	United States	80239
8	Florida Clinical Research Center, LLC	Bradenton	Florida	United States	34201
9	Florida Clinical Research Center, LLC	Maitland	Florida	United States	32751
10	Clinical Neuroscience Solutions, Inc.	Orlando	Florida	United States	32806
11	Miami Research Associates	South Miami	Florida	United States	33143
12	NeuroTrials Research, Inc.	Atlanta	Georgia	United States	30342
13	Capstone Clinical Research	Libertyville	Illinois	United States	60048
14	American Medical Research	Oak Brook	Illinois	United States	60523
15	Deaconess Clinic Gateway Health Center	Newburgh	Indiana	United States	47630
16	Clinical Trials Technology, Inc.	Prairie Village	Kansas	United States	66206
17	Louisiana Research Associates, Inc.	New Orleans	Louisiana	United States	70114
18	Potomac Grove Clinical Research Center	Gaithersburg	Maryland	United States	20877
19	Boston Clinical Trials	Boston	Massachusetts	United States	02131
20	Activmed Practices and Research	Haverhill	Massachusetts	United States	01830
21	Adams Clinical Trials, LLC	Watertown	Massachusetts	United States	02472
22	Rochester Center for Behavioral Medicine	Rochester Hills	Michigan	United States	48307
23	UMN Medical School, Dept of Psychiatry	Minneapolis	Minnesota	United States	55454
24	Scientella, LLA	Saint Louis	Missouri	United States	63141
25	Robert Lynn Horne, MD, LTD	Las Vegas	Nevada	United States	89102
26	Global Medical Inst LLC; Princeton Medical Institute	Princeton	New Jersey	United States	08540
27	Bioscience Research, LLC	Mount Kisco	New York	United States	10549
28	CNS Clinica at the Brain Resource Center	New York	New York	United States	10023
29	Radiant Research, Inc.	Akron	Ohio	United States	44311
30	Patient Priority Clinical Sites, LLC	Cincinnati	Ohio	United States	45215
31	The Craig and Frances Lindner Center of Hope	Mason	Ohio	United States	45040
32	Clinical Trials of America, Inc.	Eugene	Oregon	United States	97401
33	Sunstone Medical Research, LLC	Medford	Oregon	United States	97504
34	Oregon Center for Clinical Investigators (OCCI, Inc)	Portland	Oregon	United States	97210
35	Lehigh Center for Clinical Research	Allentown	Pennsylvania	United States	18104
36	CRI Lifetree	Philadelphia	Pennsylvania	United States	19139
37	Omega Medical Reserach	Warwick	Rhode Island	United States	02886
38	Radiant Research, Inc.	Greer	South Carolina	United States	29650
39	Clinical Research Associates, Inc.	Nashville	Tennessee	United States	37203
40	Texas Center for Drug Development, Inc.	Houston	Texas	United States	77081
41	Psychiatric Medical Associates	Plano	Texas	United States	75093
42	Radiant Research, Inc.	San Antonio	Texas	United States	78229
43	Advanced Research Institute	Ogden	Utah	United States	84405
44	NeuroScience, Inc.	Herndon	Virginia	United States	20170
45	Summit Research Network (Seattle), LLC	Seattle	Washington	United States	98104
46	Klinische Forschung Berlin-Mitte GmbH	Berlin		Germany	10117
47	Klinische Forschung Berlin Buch GmbH	Berlin		Germany	13125
48	Klinische Forschung Schwerin GmbH	Schwerin		Germany	19055

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01718509
• Other Study ID Numbers: SPD489-344; 2012-003310-14
• First Posted: Oct 31, 2012
• Last Update Posted: Jul 16, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Bulimia; Feeding and Eating Disorders; Binge-Eating Disorder; Lisdexamfetamine Dimesylate

Study Results

Participant Flow

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Period Title: Overall Study
STARTED	195	195
COMPLETED	147	147
NOT COMPLETED	48	48

Baseline Characteristics

Arm/Group Title	PLACEBO	SPD489	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	185	181	366
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	38.7 (10.01)	37.1 (10.00)	37.9 (10.02)
Age, Customized (Count of Participants)
< 40 years	90 48.6%	108 59.7%	198 54.1%
>= 40 years	95 51.4%	73 40.3%	168 45.9%
Sex: Female, Male (Count of Participants)
Female	153 82.7%	159 87.8%	312 85.2%
Male	32 17.3%	22 12.2%	54 14.8%
Region of Enrollment (Count of Participants)
GERMANY	9 4.9%	11 6.1%	20 5.5%
UNITED STATES	176 95.1%	170 93.9%	346 94.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Number of Binge Days Per Week at Visit 8 Which Spans Weeks 11/12
Description	Binge days defined as days during which at least 1 binge episode occurred. As assessed by clinical interview based on subject binge diary.
Time Frame	Baseline and Visit 8 Which Spans Weeks 11/12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	176	174
Least Squares Mean (Standard Error) [Binge days per week]	-2.26 (0.137)	-3.92 (0.135)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.66
	Confidence Interval	(2-Sided) 95%; -2.04 to -1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores
Description	Clinical Global Impression-Improvement (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.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	176	174
Number (95% Confidence Interval) [percentage of participants]	42.9 23.2%	86.2 47.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Percent of Participants With a 4-Week Cessation From Binge Eating
Description	4-week cessation from binge eating is defined as no binge eating episodes for 28 consecutive days prior to the last study visit.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	176	174
Number (95% Confidence Interval) [percentage of participants]	13.1 7.1%	36.2 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Percent Change From Baseline in Body Weight (kg) at Week 12
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	176	174
Least Squares Mean (Standard Error) [percentage change]	-0.15 (0.353)	-5.57 (0.350)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-5.41
	Confidence Interval	(2-Sided) 95%; -6.39 to -4.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) Total Score at Week 12
Description	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.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	176	174
Least Squares Mean (Standard Error) [units on a scale]	-7.42 (0.571)	-15.36 (0.563)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-7.94
	Confidence Interval	(2-Sided) 95%; -9.51 to -6.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Fasting Triglyceride Levels at Up to 12 Weeks
Time Frame	Baseline and up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Not all subjects had data for this outcome.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	153	156
Least Squares Mean (Standard Error) [mmol/L]	0.062 (0.0453)	-0.133 (0.0449)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.196
	Confidence Interval	(2-Sided) 95%; -0.321 to -0.070
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline In Fasting Total Cholesterol Levels at Up to 12 Weeks
Time Frame	Baseline and up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Not all subjects had data for this outcome.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	153	156
Least Squares Mean (Standard Error) [mmol/L]	-0.126 (0.0460)	-0.204 (0.0456)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.234
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.077
	Confidence Interval	(2-Sided) 95%; -0.205 to 0.050
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Hemoglobin A1c Levels at Up to 12 Weeks
Time Frame	Baseline and up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Not all subjects had data for this outcome.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	154	156
Least Squares Mean (Standard Error) [Percent]	-0.02 (0.017)	0.01 (0.017)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.185
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Binge Eating Response
Description	Response is based on the reduction in the number of binge eating episodes. 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
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Not all subjects had data for this outcome.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	142	145
1-week cessation	23.9 12.9%	55.9 30.9%
Marked reduction	13.4 7.2%	22.8 12.6%
Moderate reduction	19.7 10.6%	16.6 9.2%
Negative to minimal reduction	43.0 23.2%	4.8 2.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Multiplicity is not adjusted for this secondary efficacy endpoint in this study.
	Method	Cochran-Mantel-Haenszel
	Comments

10. Secondary Outcome

Title	Change From Baseline in the Number of Binge Episodes Per Week at Visit 8 Which Spans Weeks 11/12
Time Frame	Baseline and Visit 8 Which Spans Weeks 11/12

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	176	174
Least Squares Mean (Standard Error) [Binge episodes per week]	-3.31 (0.194)	-5.54 (0.193)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Multiplicity is not adjusted for this secondary efficacy endpoint in this study.
	Method	Mixed Models Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.23
	Confidence Interval	(2-Sided) 95%; -2.77 to -1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in Eating Inventory Scores at Week 12
Description	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.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	176	174
Cognitive Restraint of Eating	2.44 (0.352)	3.71 (0.347)
Disinhibition of Eating	-2.01 (0.305)	-5.61 (0.300)
Perceived Hunger	-1.93 (0.318)	-6.14 (0.313)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments	Cognitive Restraint of Eating
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments	Multiplicity is not adjusted for this secondary efficacy endpoint in this study.
	Method	Mixed Models Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95%; 0.29 to 2.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments	Disinhibition of Eating
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Multiplicity is not adjusted for this secondary efficacy endpoint in this study.
	Method	Mixed Models Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.60
	Confidence Interval	(2-Sided) 95%; -4.44 to -2.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments	Perceived Hunger
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Multiplicity is not adjusted for this secondary efficacy endpoint in this study.
	Method	Mixed Models Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-4.21
	Confidence Interval	(2-Sided) 95%; -5.09 to -3.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Binge Eating Scale (BES) Score at Week 12
Description	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 subject has greater control over eating behavior and 4 denoting that a subject 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.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	176	174
Least Squares Mean (Standard Error) [units on a scale]	-8.24 (0.781)	-17.52 (0.771)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Multiplicity is not adjusted for this secondary efficacy endpoint in this study.
	Method	Mixed Models Repeated Measures Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-9.28
	Confidence Interval	(2-Sided) 95%; -11.44 to -7.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in Frontal Systems Behavior (FrSBe) Total Score at Up to 12 Weeks
Description	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. Subjects 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.
Time Frame	Baseline and up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Not all subjects had data for this outcome.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	153	158
Least Squares Mean (Standard Error) [t-scores]	-3.09 (0.655)	-4.05 (0.644)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PLACEBO, SPD489
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.298
	Comments	Multiplicity is not adjusted for this secondary efficacy endpoint in this study.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95%; -2.77 to 0.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Mobility
Description	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.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Not all subjects had data for this outcome.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	168	169
No problems in walking about	86.9 47%	91.7 50.7%
Slight problems in walking about	8.9 4.8%	7.1 3.9%
Moderate problems walking about	3.0 1.6%	0.6 0.3%
Severe problems walking about	1.2 0.6%	0.6 0.3%
Unable to walk about	0 0%	0 0%

15. Secondary Outcome

Title	EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Self-Care
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Not all subjects had data for this outcome.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	168	169
No problems washing or dressing	97.0 52.4%	97.0 53.6%
Slight problems washing or dressing	2.4 1.3%	3.0 1.7%
Moderate problems washing or dressing	0.6 0.3%	0 0%
Severe problems washing or dressing	0 0%	0 0%
Unable to wash or dress	0 0%	0 0%

16. Secondary Outcome

Title	EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Usual Activities
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Not all subjects had data for this outcome.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	168	169
No problems doing usual activities	82.1 44.4%	89.9 49.7%
Slight problems dosin usual activities	14.3 7.7%	8.3 4.6%
Moderate problems doing usual activities	3.0 1.6%	1.2 0.7%
Severe problems doing usual activities	0.6 0.3%	0.6 0.3%
Unable to do usual activities	0 0%	0 0%

17. Secondary Outcome

Title	EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Pain/Discomfort
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Not all subjects had data for this outcome.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	168	169
No pain or discomfort	75.6 40.9%	76.3 42.2%
Slight pain or discomfort	18.5 10%	20.1 11.1%
Moderate pain or discomfort	3.0 1.6%	3.0 1.7%
Severe pain or discomfort	3.0 1.6%	0 0%
Extreme pain or discomfort	0 0%	0.6 0.3%

18. Secondary Outcome

Title	EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Anxiety/Depression
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Not all subjects had data for this outcome.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	168	169
Not anxious or depressed	69.6 37.6%	76.3 42.2%
Slightly anxious or depressed	23.2 12.5%	20.7 11.4%
Moderately anxious or depressed	4.8 2.6%	2.4 1.3%
Severely anxious or depressed	1.2 0.6%	0 0%
Extremely anxious or depressed	1.2 0.6%	0.6 0.3%

19. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale (C-SSRS)
Description	C-SSRS is a semi-structured interview that captures the occurence, 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.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

For this Outcome Measure the Safety Analysis Set is defined as all randomized subjects who took at least 1 dose of investigational product and who had at least 1 post-baseline safety assessment completed, and responded to the relevant questions for the C-SSRS. All subjects from Site 015 were excluded from the Safety Analysis Set.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	183	179
Suicidal ideation	0 0%	0 0%
Suicidal behavior	0 0%	0 0%

20. Secondary Outcome

Title	Change in Amphetamine Cessation Symptom Assessment (ACSA) Total Score From Baseline to Week 12.
Description	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. Calculated as Baseline (Day 0) - Week 12 ACSA scores.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Safety Analysis Set who completed ACSC at Baseline & Week 12 Visits.

Arm/Group Title	PLACEBO	SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks	50 or 70 mg administered orally, once-daily for up to 12 weeks
Measure Participants	142	135
Mean (Standard Deviation) [units on a scale]	7.0 (7.69)	4.6 (5.83)

Adverse Events

Adverse Event Reporting Description	The Safety Analysis Set defined as all randomized subjects who took at least 1 dose of investigational product and had at least 1 follow-up safety assessment.
Arm/Group Title	PLACEBO		SPD489
Arm/Group Description	Administered once-daily, orally, for up to 12 weeks		50 or 70 mg administered orally, once-daily for up to 12 weeks
All Cause Mortality
	PLACEBO		SPD489
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PLACEBO		SPD489
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/185 (1.1%)		1/181 (0.6%)
Injury, poisoning and procedural complications
Fibula fracture	1/185 (0.5%)	1	0/181 (0%)	0
Lumbar vertebral fracture	0/185 (0%)	0	1/181 (0.6%)	1
Nervous system disorders
Syncope	1/185 (0.5%)	1	0/181 (0%)	0
Psychiatric disorders
Agitation	1/185 (0.5%)	1	0/181 (0%)	0
Anxiety	1/185 (0.5%)	1	0/181 (0%)	0
Other (Not Including Serious) Adverse Events
	PLACEBO		SPD489
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/185 (23.2%)		100/181 (55.2%)
Gastrointestinal disorders
Constipation	1/185 (0.5%)	1	10/181 (5.5%)	10
Diarrhoea	3/185 (1.6%)	3	11/181 (6.1%)	12
Dry mouth	11/185 (5.9%)	11	60/181 (33.1%)	60
Nausea	8/185 (4.3%)	9	16/181 (8.8%)	17
General disorders
Fatigue	9/185 (4.9%)	12	17/181 (9.4%)	21
Feeling jittery	0/185 (0%)	0	10/181 (5.5%)	10
Metabolism and nutrition disorders
Decreased appetite	3/185 (1.6%)	3	11/181 (6.1%)	11
Nervous system disorders
Headache	16/185 (8.6%)	19	32/181 (17.7%)	37
Psychiatric disorders
Insomnia	6/185 (3.2%)	6	19/181 (10.5%)	19

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.