E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Binge eating disorder is characterized by recurrent, distressing episodes of uncontrolled consumption of large amounts of food (binge eating) without the inappropriate compensatory weight loss behaviors of bulimia nervosa. In May 2013, BED was formally added as a free standing diagnosis under DSM-5. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate maintenance of efficacy based on time to relapse between SPD489 (50 or 70mg) and placebo, 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 and Clinical Global Impression – Severity (CGI-S) scores for patients who responded to SPD489 by the end of the Open-label Treatment Phase.
(Relapse is defined as subject reports with at least 2 or more binge days each week for 2 consecutive weeks [14 days] prior to the visit and have a at least 2 or more point increase in CGI-S score relative to their score at the Randomized-withdrawal Baseline Visit.)
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E.2.2 | Secondary objectives of the trial |
1 To evaluate the efficacy of SPD489 as compared to placebo at Visit 21 on the number of binge-eating days per week as assessed by clinical interview based on subject diary
2 To evaluate the efficacy of SPD489 as compared to placebo at Visit 21 on the global clinical measure of severity as measured by the CGI-S scale
3 To evaluate the efficacy of SPD489 as compared to placebo at Visit 21 on the obsessive/compulsive binge eating symptoms as measured by the Y-BOCS-BE
4 To evaluate the impact of SPD489 on a measure of the perception of health and quality of life for appraisal of clinical and economic health status as assessed by EQ5D5L.
5 To evaluate the safety and tolerability of SPD489 based on the occurrence of TEAEs, vitals signs results (including weight and waist circumference), clinical laboratory results, ECG results, and the C-SSRS results .
6 To evaluate amphetamine withdrawal symptoms as measured by the ACSA in the Follow up Phase.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The subject cannot be enrolled in the study before all of the following inclusion criteria (including test results) are met:
• Subject is between 18-55 years of age (or age of majority if greater
than 18 years of age, as defined by local regulations), inclusive, at the
time of consent.
• Subject meets DSM-IV-TR criteria for a diagnosis of BED.
• Subject's BED is of at least moderate severity with subjects reporting
at least 3 binge eating days per week for the 14 days prior to the
Baseline Visit (Visit 0) as documented in the subject's binge diary. A
binge day is a day during which at least 1 binge eating episode occurs.
• Subject must have a CGI-S score superior or equal to 4 at the
Screening Visit (Visit -1) and Baseline Visit (Visit 0).
• Subject has a BMI of superior or equal to 18 and inferior or equal to 45
at the Screening Visit (Visit -1) and the Baseline Visit (Visit 0).
• Subject is able to provide written, personally signed, and dated
informed consent to participate in the study before completing any
study-related procedures.
• Subject is willing and has an understanding and ability to fully comply
with study procedures and restrictions defined in this protocol. |
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E.4 | Principal exclusion criteria |
Subjects are excluded from the study if any of the following exclusion
criteria are met:
• Subject has current diagnosis of bulimia nervosa or anorexia nervosa
as defined by the SCID-I eating disorders module.
• Subject is receiving psychotherapy (eg, supportive psychotherapy,
cognitive behavior therapy, interpersonal therapy) or weight loss
support (eg, Weight Watchers) for BED that began within the 3 months
prior to the Screening Visit (Visit -1). Subjects who are receiving
psychotherapy or weight loss support that was initiated >=3 months
prior to the Screening Visit (Visit -1) will be allowed to continue to
receive psychotherapy or weight loss support during the study only if
they agree to not make any changes in the frequency or nature of their
psychotherapy or weight loss support during the course of this study.
• Subject has a current comorbid Axis I or Axis II psychiatric disorder
that is either controlled with medications prohibited in this study or is
uncontrolled and associated with significant symptoms (note: subjects
with mild mood or anxiety symptoms that do not meet criteria for Axis I
disorder, do not require treatment based on the investigator's
assessment, and do not confound efficacy or safety assessments in the
opinion of the examining investigator may be included).
• Subject has a lifetime history of psychosis, mania, hypomania,
dementia, or ADHD.
• Subject is considered a suicide risk in the opinion of the investigator,
has previously made a suicide attempt, or is currently demonstrating
active suicidal ideation. Subjects with intermittent passive suicidal
ideation are not necessarily excluded based on the assessment of the
investigator.
• Subject has a recent history (within the past 6 months) of suspected
substance abuse or dependence disorder in accordance with DSM-IV-TR
criteria. Subjects with a lifetime history of amphetamine, cocaine, or
other stimulant abuse and/or dependence will be excluded. Nicotine
dependence is not exclusionary.
• Subject has a concurrent chronic or acute illness (such as severe
allergic rhinitis, an infectious process requiring antibiotics, or diabetes),
disability, or other condition that might confound the results of safety
assessments administered in the study or that might increase risk to the
subject. Subject will be excluded if he or she has any additional
condition(s) that in the investigator's opinion would prohibit the subject from completing the study or would not be in the best interest of the
subject to participate in the study. This would include any significant
illness or unstable medical condition that could lead to difficulty in
complying with the protocol. Mild, stable asthma is not exclusionary.
• 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 that may place them at
increased vulnerability to the sympathomimetic effects of a stimulant
medication.
• Subject has a known family history of sudden cardiac death or
ventricular arrhythmia.
• Subject has any clinically significant ECG prior to the Baseline Visit
(Visit 0).
• Subject has any clinically significant laboratory abnormality prior to
the Baseline Visit (Visit 0). Subjects with hypokalemia at the Screening
Visit or prior to the Baseline Visit (Visit 0) will be excluded.
• Subject has a history of moderate or severe hypertension or has a
resting average (of 3 readings) sitting systolic blood pressure
>139mmHg or an average (of 3 readings) diastolic blood pressure
>89mmHg at the Screening Visit (Visit -1) and/or Baseline Visit (Visit
0). NOTE: Subjects with mild (Stage 1), well-controlled hypertension on
a stable antihypertensive treatment regimen, defined as having
maintained the current dose for a period of at least 3 months or longer
at the time of the Screening Visit (Visit -1), are allowed. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to relapse from randomization (Visit 8). The time of relapse is defined as the visit date when the relapse is confirmed. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Subject Daily Diary Visit 8 - Visit 21 |
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E.5.2 | Secondary end point(s) |
1. Change from Visit 8 (Week 12) to Visit 21 (Week 38) in the number of binge days per week
2. CGI-S at Visit 21/ET (Week 38)
3. Change from Visit 8 (Week 12) to Visit 21 (Week 38) in Y-BOCS-BE
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Subject Daily Diary Visit 8 - Visit 21
2. CGI-S: Visit 21/ET
3. Y-BOCS-BE: Visit 8 and Visit 21
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open-label, Dose Optimization followed by randomisation based on response |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is signified by the last patient finishing the last visit (the Follow-up Visit) of the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |