8 Week Multi-site Study of MYDAYIS® for Bipolar Depression

Study Overview
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Brief Summary
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This protocol is a Phase 2 multi-site study which aims to evaluate the safety and effectiveness of MYDAYIS&#174; as adjunctive therapy for adults with bipolar depression. Results from this study WILL NOT be used to contribute to an approval of MYDAYIS &#174; for this indication.

Official Title
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An 8 Week Randomized Double Blind Placebo Controlled Multi-site Study Assessing Efficacy and Safety of MYDAYIS&#174; (D-amphetamine / L-amphetamine) for Bipolar Depression

Conditions
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Bipolar Depression

Intervention / Treatment
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* Drug: Mydayis Extended-Release Capsule
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female between 18 and 55 years of age Bipolar I or II disorder as confirmed by structured diagnostic interview by Axis I of the SCID by DSM-IV-TR. Currently experiencing a major depressive episode unresponsive to stable (i.e. at least 4 weeks) anti-manic mood stabilizers (lithium, valproate) and/or antipsychotic therapy, with or without concomitant antidepressant therapy. Symptom severity score ≥11 on the self-report version of the Quick Inventory for Depressive Symptomatology (QIDS-SR16) or score ≥11 on the Quick Inventory for Depressive Symptomatology - Clinician (QIDS-C16) and ≥ 3 on the Clinical Global Impression for Bipolar Illness (CGI-BP) Depression Severity Scale. Patients with a comorbid attention deficit disorder and binge eating disorder will be included. Patients will be allowed to continue with their behavioral treatments (ie. CBT) targeted at their primary diagnosis. Exclusion Criteria Ability to provide informed consent and understand fully English and score ≥ 90% on comprehension test questionnaire that reviews study goals. Clinically significant signs of suicidality from any of the following assessments: Response ≥ 4 on MADRS question # 10 Response ≥2 on QIDS-C or QIDS-SR question # 12 Yes response on Columbia Suicide Severity Scale (CSSR) Question # 3 (ideation without plan or intent) ,Question #4 (ideation with intent, but no plan), or Question # 5 (ideation, intent, and plan) Suicide attempt within the past year, as defined by the Columbia-Suicide Severity Scale Known lifetime history of DSM-IV-TR diagnosis of cocaine or methamphetamine abuse or dependence. Nicotine dependence will be an exception. Positive toxicology screen for drugs of abuse (ie. cocaine, methamphetamine, cannabis, opiates) Known history of prescription abuse of stimulants. Lifetime history of stimulant-induced mania Active abuse or dependence of alcohol, opiates or cannabis that is either current or less than 3 months full remission. Baseline Young Mania Rating Scale (YMRS) score ≥ 8 Patients with active psychosis identified by SCID or a diagnosis of schizophrenia, schizoaffective disorder, delusional or schizophreniform disorder. Known hypersensitivity, such as angioedema or anaphylaxis, to amphetamines or other ingredients of MYDAYIS. Clinically unstable medical disease Known history of a structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormality, coronary artery disease, stroke or other serious cardiovascular problems. ECG with significant arrhythmias, conduction abnormalities, or voltage criteria met for left ventricular hypertrophy (unless cleared by cardiology consultation). Uncontrolled hypertension (>160/100) or tachycardia (heart rate >110) History of grand mal seizure; history of febrile seizure as infant permitted Established vasculopathy or history of Raynaud's phenomena Narrow angle glaucoma Patients with end stage renal disease (ESRD). Concomitant treatment with monoamine oxidase inhibitors (MAOIs), and also within 14 days following discontinuation of treatment with a monoamine oxidase inhibitor. Tourette's syndrome Women who are pregnant, lactating or of child-bearing potential and not using at least one adequate contraceptive measure (i.e. hormonal contraception-birth control pills-, intrauterine devices (IUD), tubal ligation or condoms during sexual intercourse) Men who do not use adequate measures (male condoms).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mydayis - Active<br>MYDAYIS®, Oral administration, dose regimen for Double blind phase and open label phase. 12.5 mg x 7 days. 25 mg x 7 days 37.5 mg x 14 days 50 mg daily x 28 days | Drug: Mydayis Extended-Release Capsule<br>* Randomized, parallel - group, double-blind, placebo-controlled, flexible-dose adjunctive trial of MYDAYIS®<br>* Other names: d-amphetamine / l-amphetamine;|
| Placebo Comparator: Placebo<br>Matching placebo, Oral administration, dose regimen for Double blind phase and open label phase. 12.5 mg x 7 days. 25 mg x 7 days 37.5 mg x 14 days 50 mg daily x 28 days | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) score | Reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score (Range: 0-60) between Baseline and Week 8 visit 10 | Baseline to week 8 visit 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quick Inventory for Depressive Symptomatology (QIDS-C and QIDS-SR) score | Reduction in Clinician and self-report symptoms of depression as measured by the Quick Inventory for Depressive Symptomatology (QIDS-C and QIDS-SR) (Range: 0-27) | Baseline to Week 8 visit 10 | 
| Remission | Treatment remission (Montgomery-Asberg Depression Rating Scale (MADRS) score < 10) (Range 0-60) | Baseline to Week 8 visit 10 | 
| Change in General Anxiety Disorder 7-item scale score | Self-report anxiety as measured by the General Anxiety Disorder 7-item scale (GAD-7) (Range: 0-21) | Baseline to Week 8 visit 10 | 
| Response | Treatment response (50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score (Range: 0-60) | Baseline to Week 8 visit 10 | 
| Change in Clinical Global Impression for Bipolar Disorder (CGI-BP) score | Percentage of much or very much improved as measured by the Clinical Global Impression for Bipolar Disorder (CGI-BP) (Range: 1-8) | Baseline to Week 8 visit 10 | 
| Change in Young Mania Rating Scale (YMRS) score | Reduction in sub-syndromal manic symptoms as measured by the Young Mania Rating Scale (YMRS) (Range: 0-56) | Baseline to Week 8 visit 10 | 
| Change in Epworth Sleepiness Scale (ESS) score | Self-report likelihood of falling asleep during normal daily situations as measured by the Epworth Sleepiness Scale (ESS) (Range: 0-24) | Baseline to Week 8 visit 10 | 
| Change in Fatigue Severity Scale (FSS) score | Self-report measure of fatigue as measured by the Fatigue Severity Scale (FSS) (Range: 0-63) | Baseline to Week 8 visit 10 | 
| Change in Binge Eating Scale (BES) score | Self-report binge eating behavior as measured by the Binge Eating Scale (BES) (Range: 0-48) | Baseline to Week 8 visit 10 | 
| Change in Morningness-Eveningness Questionnaire (MEQ) score | Self-Report measure on the Morningness-Eveningness Questionnaire (MEQ) (Range: 16-86) | Baseline to Week 8 visit 10 | 
| Change in Rapid Eating and Activity Assessment for Patients (REAP) score | Self-Report measure on Rapid Eating and Activity Assessment for Patients (REAP) (Range: 0-27) | Baseline to Week 8 visit 10 | 
| Change in Digit Symbol Substitution Test (DSST) score | Improvement in cognition as measured by the Digit Symbol Substitution Test (DSST) (Range: 0-100) | Baseline to Week 8 visit 10 |