Dasotraline Adult ADHD Study

Study Overview
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Brief Summary
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This is a randomized, double blind, multicenter, parallel group, outpatient study evaluating the efficacy and safety of dasotraline in adults with ADHD.

Detailed Description
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This is a randomized, double blind, multicenter, parallel group, outpatient study evaluating the efficacy and safety of dasotraline in adults with ADHD using 2 doses of dasotraline (4 mg/day or 6 mg/day) versus placebo over an 8 week treatment period (8 weeks of active treatment followed by a 2-week withdrawal phase).

Official Title
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A Randomized, Double Blind, Multicenter, Placebo Controlled, Parallel Group, Efficacy and Safety Study of 2 Doses of Dasotraline in Adults With Attention Deficit Hyperactivity Disorder (ADHD)

Conditions
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Adult Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Dasotraline
* Drug: Dasotraline
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is male or female, 18 to 55 years old, inclusive, at the time of informed consent. Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM 5) criteria for a primary diagnosis of ADHD (inattentive, hyperactive, or combined subtype) established by a comprehensive psychiatric evaluation that reviews psychiatric criteria. Diagnosis is confirmed by Adult ADHD Clinical Diagnostic Scale (ACDS). Note: The diagnosis of ADHD and appropriateness of inclusion in the trial will be independently confirmed by external expert review. Experts will review diagnostic and other screening instruments for each subject and approval is required before a subject can be randomized. The Mini International Neuropsychiatric Interview (MINI) will be administered to confirm the absence of any other comorbid psychiatric disorders. Subject has an ADHD RS IV with adult prompts total score of ≥ 26 at screening and at Baseline. Subject has a CGI S score of ≥ 4 at screening and at Baseline. Subject has a negative breath alcohol test and a negative urine drug screen (UDS) for any illicit drug at screening. If the subject has a positive drug screen for ADHD medications (eg, amphetamine) at screening, the subject must have a negative repeat UDS at least 7 days before baseline. Subject is male or a non pregnant, non lactating female. Female subjects must have a negative serum pregnancy test at screening; females who are post menopausal (defined as at least 12 months of spontaneous amenorrhea) and those who have undergone hysterectomy or bilateral oophorectomy will be exempted from the pregnancy test. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use an effective and medically acceptable form of birth control, as defined in Section 10.4, throughout the study period. Note: Continued use of an effective and medically acceptable form of birth control is recommended for 30 days after study completion. Subject must have a stable living arrangement that allows for consistent participation for the full duration of the study. Subject must be able to comply with study medication administration and adhere to protocol requirements. Subject can read well enough to understand the informed consent form and other subject materials. Subjects must complete a practice trial for the TASS assessment at one timepoint during Screening. Exclusion Criteria: Subject has a ≥ 25% improvement on the ADHD RS IV total score between screening and baseline. Subject has a psychiatric disorder other than ADHD that has been the primary focus of treatment at any time during the 12 months before screening. Subject has a past history of, or current presentation consistent with, bipolar disorder (including bipolar I and bipolar II), schizophrenia, schizoaffective disorder, or any other psychotic disorder; a personality disorder per DSM 5 criteria. Subject has a history of drug dependence or Substance Related Disorder (excluding nicotine and caffeine) within the 12 months before screening, as defined by DSM 5 criteria. -- Subject has Hamilton Anxiety Rating Scale (HAM A) total score ≥ 21 at screening and baseline. Subject has PSQI total score ≥ 8 at screening or baseline or moderate to severe insomnia as determined by the Investigator. Subject has a history of non-response (per clinician judgment) to two adequate treatment regimens of stimulant or non-stimulant treatment for ADHD. Subject has a history of epilepsy, seizures (except childhood febrile seizures), unexplained syncope or other unexplained blackouts (except single incident), or head trauma with loss of consciousness lasting more than 5 minutes, or a history of clinically significant multiple head traumas without loss of consciousness. Subject has an acute or chronic medical condition (other than ADHD) that in the opinion of the investigator could confound clinical assessments or interfere with the ability of the subject to participate in the study. Subject is currently taking or has taken within 6 weeks prior to screening an antidepressent medication; antipsychotic medication; or lithium (any lithium preparation or formulation). Subject is currently taking or has taken within the previous 6 months an anticonvulsant medication (eg, phenytoin, carbamazepine, lamotrigine, valproic acid); antipsychotic medication; or lithium (any lithium preparation or formulation). Subject is currently taking an alpha 2 adrenergic receptor agonist (including clonidine and guanfacine). Subject has a life-time history of a pattern of abuse or diversion of stimulants. Subject has a body mass index (BMI) less than 18 or greater than 35 kg/m2 at screening or baseline. Subject answers yes to suicidal ideation item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C SSRS assessment at screening (in the past month). Subjects who answer yes to this question must be referred to the Investigator for follow up evaluation. Subject has attempted suicide within 2 years before the screening period. Subject has history of positive test for Hepatitis B surface antigen or Hepatitis C antibody and has liver function test results at screening above the upper limit of normal (ULN) for the reference laboratory. Subject is known to have tested positive for human immunodeficiency virus (HIV). Subject has a clinically significant abnormality on screening evaluation including physical examination, vital signs, ECG, or laboratory tests that the Investigator considers to be inappropriate to allow participation in the study. The subject's screening ECG shows a corrected QT interval using Fridericia's formula (QTcF) of ≥ 450 msec for male subjects or ≥ 470 msec for female subjects. Eligibility will be based on the core laboratory ECG interpretation report. The subject's screening hematology results show an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value ≥ 2 times the ULN, or a blood urea nitrogen (BUN) value ≥ 1.5 times the ULN for the reference range. Subject has a history of allergic reaction or has a known or suspected sensitivity to any substance that is contained in the study medication formulation. Subject is currently participating or has participated in a clinical trial within the last 90 days or has participated in more than 2 clinical trials within the past year. This includes studies using marketed compounds or devices. Note: Subjects will be checked for multiple study enrollments by site staff. Subject has been incarcerated in a prison within 12 months prior to Screening. Subject has previously been randomized in a clinical trial of dasotraline. Subject is an investigational site staff member or the relative of an investigational site staff member.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dasotraline 4 mg<br>Dasotraline 4 mg once daily | Drug: Dasotraline<br>* Dasotraline 4 mg once daily<br>|
| Experimental: Dasotraline 6 mg<br>Dasotraline 6 mg once daily | Drug: Dasotraline<br>* Dasotraline 6 mg once daily<br>|
| Placebo Comparator: Placebo<br>Placebo once daily | Other: Placebo<br>* Placebo once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline at Week 8 in ADHD symptoms measured by the ADHD Rating Scale Version IV (ADHD RS IV) with adult prompts total score. |  | 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in ADHD symptoms measured with the ADHD Rating Scale Version IV (ADHD RS IV) with adult prompts total score at Weeks 1, 2, 4, and 6. |  | 8 Weeks | 
| Change from baseline in the inattentiveness and hyperactivity-impulsivity subscale scores of the ADHD Rating Scale Version IV (ADHD RS IV) with adult prompts at Weeks 1, 2, 4, 6, and 8. |  | 8 Weeks | 
| Change from baseline in Clinical Global Impression - Severity scale (CGI S) scale at Weeks 1, 2, 4, 6, and 8. |  | 8 Weeks | 
| Change from baseline in Sheehan Depression Scale (SDS) total score at Weeks 4 and 8. |  | 8 Weeks | 
| Change from baseline in Sheehan Depression Scale (SDS) domain scores: work/school, family life, social life at Weeks 4 and 8. |  | 8 Weeks | 
| Change from baseline in Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF A) Global Executive Composite score and Behavioral Regulation Index (BRI) and Metacognition Index (MI) at Weeks 4 and 8. |  | 8 Weeks | 
| Change from baseline in ADHD Impact Module - Adult AIM A in global domain scores at Weeks 4 and 8. |  | 8 Weeks | 
| Time sensitive ADHD Symptom Scale (TASS) total score and subscale scores (Inattention and Hyperactive impulsive) at Weeks 3, 5, and 7. |  | 8 Weeks | 
| Change from baseline in Adult ADHD Self Report Scale (Version 1.1) (ASRS) total score and subscale scores (inattention, hyperactivity-impulsivity, executive function, emotional control, and impulsivity) at each week. |  | 8 Weeks | 
| Adult ADHD Medication Smoothness of Effect Scale (AMSES) score at Weeks 2, 4, 6, and 8. |  | 8 Weeks | 
| Change from baseline in Pittsburgh Sleep Quality Index (PSQI) global score and 7 component scores at Weeks 2, 4, and 8. |  | 8 Weeks | 
| The incidence of overall AEs, serious AEs (SAEs), and AEs (or SAEs) leading to discontinuations. |  | 8 Weeks | 
| Clinical laboratory evaluations (serum chemistry). |  | 8 Weeks | 
| Clinical laboratory evaluations ( lipid panel). |  | 8 Weeks | 
| Clinical laboratory evaluations (thyroid function panel). |  | 8 Weeks | 
| Clinical laboratory evaluations (hematology). |  | 8 Weeks | 
| Clinical laboratory evaluations (urinalysis). |  | 8 Weeks | 
| Clinical evaluations (vital signs). |  | 8 Weeks | 
| Clinical evaluations (orthostatic effects). |  | 8 Weeks | 
| Clinical evaluations (physical examinations). |  | 8 Weeks | 
| Clinical evaluations (body weight). |  | 8 Weeks | 
| Clinical evaluations (12 lead ECGs). |  | 8 Weeks | 
| Frequency and severity of suicidal ideation and suicidal behavior as assessed by the C SSRS. |  | 8 Weeks | 
| Drug Effects Questionnaire (DEQ) scores at Weeks 1, 2, 4, 6, and 8. |  | 8 Weeks | 
| Symptoms of withdrawal by Physician Withdrawal Checklist (PWC) scores at Week 8, 9, and 10. |  | 10 Weeks | 
| Symptoms of withdrawal by Study Medication Withdrawal Questionnaire (SMWQ) scores at Weeks 9 and 10. |  | 10 Weeks | 
| Symptoms of withdrawal by Hamilton Anxiety Rating Scale (HAM A) scores at Weeks 8, 9, and 10. |  | 10 Weeks | 
| Symptoms of withdrawal by Montgomery-Asberg Depression Rating Scale (MADRS) scores at Weeks 8, 9, and 10. |  | 10 Weeks |