Clinical Trial Results:
The SPD489-343, 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
Summary
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EudraCT number |
2012-003309-91 |
Trial protocol |
SE DE ES |
Global end of trial date |
25 Sep 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
24 Feb 2016
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First version publication date |
13 Mar 2015
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Other versions |
v1 (removed from public view) |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SPD489-343
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01718483 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Shire Development, LLC
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Sponsor organisation address |
725 Chesterbrook Boulevard Wayne, Pennsylvania, United States, 19087
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Public contact |
Medical Communications, Shire Pharmaceuticals Ltd, +44 8000556614, medinfoglobal@shire.com
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Scientific contact |
Medical Communications, Shire Pharmaceuticals Ltd, +44 8000556614, medinfoglobal@shire.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Oct 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Sep 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To demonstrate the efficacy of SPD489 compared with placebo in adults (18-55 years of age inclusive) with moderate to severe binge eating disorder (BED) at Visit 8 (Weeks 11-12) 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.
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Protection of trial subjects |
This study was conducted in accordance with International Conference on Harmonisation of Good Clinical Practice, the principles of the Declaration of Helsinki, as well as other applicable local ethical and legal requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Nov 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 10
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Country: Number of subjects enrolled |
Sweden: 29
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Country: Number of subjects enrolled |
Germany: 3
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Country: Number of subjects enrolled |
United States: 341
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Worldwide total number of subjects |
383
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EEA total number of subjects |
42
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
383
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were recruited between 12-Nov-2012 and 19-June-2013 and locations included medical clinics & research centers. | |||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 383 subjects were randomized to treatment. Of these, 4 subjects from the placebo arm discontinued the study prior to study drug administration (reasons for discontinuation for 4 'randomized but not treated' subjects were: 2 subjects lost to follow-up and 2 withdrew due to protocol violation). A total of 379 subjects started treatment. | |||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Double-blind Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||||||||||||||||||||||||||
Arm description |
Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks. | |||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks.
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Arm title
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SPD489 | |||||||||||||||||||||||||||||||||
Arm description |
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. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lisdexamfetamine dimesylate
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Investigational medicinal product code |
SPD489
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Other name |
LDX, Vyvanse®, Elvanse, Tyvense, Elvanse Adult, Elvanse Vuxen, Aduvanz
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
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.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: All enrolled subjects were not treated with study drug. Since baseline included treated subjects only, the worldwide number enrolled in the trial differs with the number of subjects reported in the baseline period. |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SPD489
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks. | ||
Reporting group title |
SPD489
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Reporting group description |
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. |
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End point title |
Change From Baseline in the Number of Binge Days Per Week at Visit 8 (Weeks 11-12) | |||||||||||||||
End point description |
Binge days defined as days during which at least 1 binge episode occurred. As assessed by clinical interview based on subject binge diary.
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 (number of binge days per week calculated for at least 1 week).
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End point type |
Primary
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End point timeframe |
Baseline and Visit 8 (Weeks 11-12)
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Statistical analysis title |
Number of Binge Days Per Week at Visit 8 | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
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Comparison groups |
Placebo v SPD489
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Number of subjects included in analysis |
374
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
Mixed Models Repeated Measures Analysis | |||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||
Point estimate |
-1.35
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-1.7 | |||||||||||||||
upper limit |
-1.01 | |||||||||||||||
Notes [1] - Placebo controlled |
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End point title |
Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | |||||||||||||||
End point description |
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.
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 (number of binge days per week calculated for at least 1 week).
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End point type |
Secondary
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End point timeframe |
Up to 12 weeks
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Statistical analysis title |
Improvement on CGI-I Score | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
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Comparison groups |
Placebo v SPD489
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Number of subjects included in analysis |
374
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | |||||||||||||||
P-value |
< 0.001 [3] | |||||||||||||||
Method |
Chi-squared | |||||||||||||||
Confidence interval |
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Notes [2] - Placebo controlled [3] - Placebo controlled |
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End point title |
Percent of Subjects With a 4-Week Cessation From Binge Eating | |||||||||||||||
End point description |
4-week cessation from binge eating is defined as no binge eating episodes for 28 consecutive days prior to the last study visit.
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 (number of binge days per week calculated for at least 1 week).
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End point type |
Secondary
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End point timeframe |
Up to 12 weeks
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Statistical analysis title |
Four-Week Cessation From Binge Eating | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
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Comparison groups |
Placebo v SPD489
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Number of subjects included in analysis |
374
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Analysis specification |
Pre-specified
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Analysis type |
other [4] | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
Chi-squared | |||||||||||||||
Confidence interval |
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Notes [4] - Placebo controlled |
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End point title |
Percent Change From Baseline in Body Weight at Week 12 | |||||||||||||||
End point 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 (number of binge days per week calculated for at least 1 week).
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End point type |
Secondary
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End point timeframe |
Baseline and week 12
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Statistical analysis title |
Percent Change in Body weight | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
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Comparison groups |
SPD489 v Placebo
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Number of subjects included in analysis |
374
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Analysis specification |
Pre-specified
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Analysis type |
other [5] | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
Mixed Models Repeated Measures Analysis | |||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||
Point estimate |
-6.35
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-7.17 | |||||||||||||||
upper limit |
-5.54 | |||||||||||||||
Notes [5] - Placebo controlled |
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End point title |
Change From Baseline in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) Total Score at Week 12 | |||||||||||||||
End point 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.
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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
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End point type |
Secondary
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End point timeframe |
Baseline and week 12
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Statistical analysis title |
Y-BOCS-BE Total Score at Week 12 | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
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Comparison groups |
Placebo v SPD489
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Number of subjects included in analysis |
371
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Analysis specification |
Pre-specified
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Analysis type |
other [6] | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
Mixed Models Repeated Measures Analysis | |||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||
Point estimate |
-7.4
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-8.93 | |||||||||||||||
upper limit |
-5.88 | |||||||||||||||
Notes [6] - Placebo controlled |
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End point title |
Change From Baseline in Fasting Triglyceride Levels at Up to 12 Weeks | |||||||||||||||
End point 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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12/Early termination (ET)
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Statistical analysis title |
Fasting Triglyceride Levels at Up to 12 Weeks | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
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Comparison groups |
Placebo v SPD489
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Number of subjects included in analysis |
373
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Analysis specification |
Pre-specified
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Analysis type |
other [7] | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
ANCOVA | |||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||
Point estimate |
-0.199
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.31 | |||||||||||||||
upper limit |
-0.088 | |||||||||||||||
Notes [7] - Placebo controlled |
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End point title |
Change From Baseline In Fasting Total Cholesterol Levels at Up to 12 Weeks | |||||||||||||||
End point 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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12/ET
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Statistical analysis title |
Fasting Total Cholesterol Levels at Up to 12 Weeks | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
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Comparison groups |
Placebo v SPD489
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Number of subjects included in analysis |
373
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Analysis specification |
Pre-specified
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Analysis type |
other [8] | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
ANCOVA | |||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||
Point estimate |
-0.211
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.33 | |||||||||||||||
upper limit |
-0.092 | |||||||||||||||
Notes [8] - Placebo controlled |
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End point title |
Change From Baseline in Hemoglobin A1c Levels at Up to 12 Weeks | |||||||||||||||
End point 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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12/ET
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Statistical analysis title |
Hemoglobin A1c Levels at Up to 12 Weeks | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
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Comparison groups |
Placebo v SPD489
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Number of subjects included in analysis |
370
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Analysis specification |
Pre-specified
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Analysis type |
other [9] | |||||||||||||||
P-value |
= 0.308 | |||||||||||||||
Method |
ANCOVA | |||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||
Point estimate |
-0.02
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.07 | |||||||||||||||
upper limit |
0.02 | |||||||||||||||
Notes [9] - Placebo controlled |
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End point title |
Binge Eating Response | ||||||||||||||||||||||||
End point description |
Response is based on the reduction in the number of binge eating episodes. Percentage of subjects 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.
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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
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End point type |
Secondary
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End point timeframe |
Week 12/ET
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Statistical analysis title |
Binge Eating Response | ||||||||||||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
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Comparison groups |
Placebo v SPD489
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Number of subjects included in analysis |
371
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Analysis specification |
Pre-specified
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Analysis type |
other [10] | ||||||||||||||||||||||||
P-value |
< 0.001 [11] | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Confidence interval |
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Notes [10] - Placebo controlled [11] - Multiplicity is not adjusted for this secondary efficacy endpoint in this study. |
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End point title |
Change From Baseline in the Number of Binge Episodes Per Week at Visit 8 (Weeks 11-12) | |||||||||||||||
End point 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 (number of binge days per week calculated for at least 1 week).
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End point type |
Secondary
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End point timeframe |
Baseline and Visit 8 (Weeks 11-12)
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Statistical analysis title |
Number of Binge Episodes Per Week at Visit 8 | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
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Comparison groups |
Placebo v SPD489
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Number of subjects included in analysis |
374
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Analysis specification |
Pre-specified
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Analysis type |
other [12] | |||||||||||||||
P-value |
< 0.001 [13] | |||||||||||||||
Method |
Mixed Models Repeated Measures Analysis | |||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||
Point estimate |
-1.77
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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|||||||||||||||
lower limit |
-2.24 | |||||||||||||||
upper limit |
-1.3 | |||||||||||||||
Notes [12] - Placebo controlled [13] - Multiplicity is not adjusted for this secondary efficacy endpoint in this study. |
|
||||||||||||||||||||||
End point title |
Change From Baseline in Eating Inventory Scores at Week 12 | |||||||||||||||||||||
End point description |
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.
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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline and week 12
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Statistical analysis title |
Cognitive Restraint of Eating | |||||||||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
|
|||||||||||||||||||||
Comparison groups |
Placebo v SPD489
|
|||||||||||||||||||||
Number of subjects included in analysis |
372
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [14] | |||||||||||||||||||||
P-value |
< 0.001 [15] | |||||||||||||||||||||
Method |
Mixed Models Repeated Measures Analysis | |||||||||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||||||||
Point estimate |
1.65
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
0.72 | |||||||||||||||||||||
upper limit |
2.57 | |||||||||||||||||||||
Notes [14] - Placebo controlled [15] - Multiplicity is not adjusted for this secondary efficacy endpoint in this study. |
||||||||||||||||||||||
Statistical analysis title |
Disinhibition of Eating | |||||||||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
|
|||||||||||||||||||||
Comparison groups |
Placebo v SPD489
|
|||||||||||||||||||||
Number of subjects included in analysis |
372
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [16] | |||||||||||||||||||||
P-value |
< 0.001 [17] | |||||||||||||||||||||
Method |
Mixed Models Repeated Measures Analysis | |||||||||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||||||||
Point estimate |
-4.19
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-4.98 | |||||||||||||||||||||
upper limit |
-3.39 | |||||||||||||||||||||
Notes [16] - Placebo controlled [17] - Multiplicity is not adjusted for this secondary efficacy endpoint in this study. |
||||||||||||||||||||||
Statistical analysis title |
Perceived Hunger | |||||||||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
|
|||||||||||||||||||||
Comparison groups |
Placebo v SPD489
|
|||||||||||||||||||||
Number of subjects included in analysis |
372
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [18] | |||||||||||||||||||||
P-value |
< 0.001 [19] | |||||||||||||||||||||
Method |
Mixed Models Repeated Measures Analysis | |||||||||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||||||||
Point estimate |
-4.7
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-5.49 | |||||||||||||||||||||
upper limit |
-3.91 | |||||||||||||||||||||
Notes [18] - Placebo controlled [19] - Multiplicity is not adjusted for this secondary efficacy endpoint in this study. |
|
||||||||||||||||
End point title |
Change From Baseline in Binge Eating Scale (BES) Score at Week 12 | |||||||||||||||
End point 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.
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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Baseline and week 12
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
BES Score at Week 12 | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
|
|||||||||||||||
Comparison groups |
Placebo v SPD489
|
|||||||||||||||
Number of subjects included in analysis |
373
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
other [20] | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
Mixed Models Repeated Measures Analysis | |||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||
Point estimate |
-10.32
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
-12.43 | |||||||||||||||
upper limit |
-8.21 | |||||||||||||||
Notes [20] - Placebo controlled |
|
||||||||||||||||
End point title |
Change From Baseline in Frontal Systems Behavior (FrSBe) Total Score at Week 12 | |||||||||||||||
End point 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.
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). Not all subjects had data for this outcome.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Baseline and week 12
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
FrSBe Total Score at Week 12 | |||||||||||||||
Statistical analysis description |
Analysis was SPD489 vs Placebo
|
|||||||||||||||
Comparison groups |
Placebo v SPD489
|
|||||||||||||||
Number of subjects included in analysis |
369
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
other [21] | |||||||||||||||
P-value |
= 0.706 | |||||||||||||||
Method |
ANCOVA | |||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||
Point estimate |
-0.31
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
-1.93 | |||||||||||||||
upper limit |
1.31 | |||||||||||||||
Notes [21] - Placebo controlled |
|
||||||||||||||||||||||||||||
End point title |
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Mobility | |||||||||||||||||||||||||||
End point 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. Percentage of subjects with various mobility conditions were reported.
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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Up to 12 weeks
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Self-Care | |||||||||||||||||||||||||||
End point 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. Percentage of subjects with various self-care conditions were reported.
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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Up to 12 weeks
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Usual Activities | |||||||||||||||||||||||||||
End point 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. Percentage of subjects with various usual activities conditions were reported.
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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Up to 12 weeks
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Pain/Discomfort | |||||||||||||||||||||||||||
End point 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. Percentage of subjects with various pain/discomfort conditions were reported.
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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Up to 12 weeks
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Anxiety/Depression | |||||||||||||||||||||||||||
End point 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. Percentage of subjects with various anxiety/depression conditions were reported.
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 (number of binge days per week calculated for at least 1 week). Not all subjects had data for this outcome.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Up to 12 weeks
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Columbia-Suicide Severity Rating Scale (C-SSRS) | ||||||||||||||||||
End point description |
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.
The Safety Analysis Set was 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. Not all subjects had data for this outcome.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to 12 weeks
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Amphetamine Cessation Symptom Assessment (ACSA) Total Score | ||||||||||||
End point 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.
The Safety Analysis Set was 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. Not all subjects had data for this outcome.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 12 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first dose of study drug up to 3 days after the last dose at up to 12 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.1
|
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PLACEBO
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo matching SPD489 capsule administered orally, once-daily for up to 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SPD489
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
12 Nov 2012 |
• Added an Overall Risk/Benefit Assessment
• Changed comparison of the Y-BOCS-BE total score to a key secondary objective
• Added assessments of the EQ-5D-5L at Weeks 4, 6, 8, and 10 (Visits 4, 5, 6, and 7)
• Clarified inclusion criterion to further describe indeterminate pregnancy test results
• Clarified exclusion criterion to state a current diagnosis, rather than concurrent symptoms, of bulimia nervosa or anorexia nervosa was exclusionary
• Added language regarding contraception requirements being reviewed at every study visit and document in source document
• Clarified language regarding use of psychoactive medications during the study and before study entry, and changed the language of the permitted window for psychotherapy
• Clarified that the Mini International Neuropsychiatric Interview (MINI-Plus) was to be used to exclude comorbid Axis I disorders rather than confirm diagnosis of BED
• Added further language addressing the management of positive responses on the C-SSRS
• Clarified that the ACSA was to be collected at the Baseline Visit (Visit 0)
• Added a ±2-hour window to the 7:00 AM dosing instructions
• Added smoking status to items collected as part of medical history |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |