Dasotraline Adult ADHD Study

Phase 3

Completed

Conditions: Adult Attention Deficit Hyperactivity Disorder

Interventions: Drug: Dasotraline
Other: Placebo

Registration Number: NCT02276209

Lead Sponsor: Sumitomo Pharma America, Inc.

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

Detailed Description: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 636

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dasotraline 4 mg	Dasotraline	Dasotraline 4 mg once daily
Placebo	Placebo	Placebo once daily
Dasotraline 6 mg	Dasotraline	Dasotraline 6 mg once daily

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
The incidence of overall AEs, serious AEs (SAEs), and AEs (or SAEs) leading to discontinuations.	8 Weeks
Clinical laboratory evaluations (serum chemistry).	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
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
Symptoms of withdrawal by Montgomery-Asberg Depression Rating Scale (MADRS) scores at Weeks 8, 9, and 10.	10 Weeks

Trial Locations

Locations (57): Gulfcoast Clinical Research
🇺🇸
Fort Myers, Florida, United States
Kennedy Krieger Institute
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Baltimore, Maryland, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
Premier Psychiatric Research Institute, LLC
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Lincoln, Nebraska, United States
Miami Research Associates
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Miami, Florida, United States
Bayou City Research Corporation
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Houston, Texas, United States
Pharmacology Research Institute
🇺🇸
Encino, California, United States
ConnecticutClinicalResearch
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Cromwell, Connecticut, United States
SummitResearchNetwork
🇺🇸
Portland, Oregon, United States
Southern California Research LLC
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Beverly Hills, California, United States
Oregon Center for Clinical Investigations, Inc.
🇺🇸
Salem, Oregon, United States
Eastside Comprehensive Medical Center, LLC
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New York, New York, United States
Collaborative Neuroscience Network, LLC
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Garden Grove, California, United States
Coastal Carolina Research Center
🇺🇸
Mount Pleasant, South Carolina, United States
Preferred Research Partners
🇺🇸
Little Rock, Arkansas, United States
Elite Clinical Trials, Inc.
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Wildomar, California, United States
Center for Emotional Fitness
🇺🇸
Cherry Hill, New Jersey, United States
iResearch Atlanta, LLC
🇺🇸
Decatur, Georgia, United States
University of Cincinnati, Department of Psychiatry
🇺🇸
Cincinnati, Ohio, United States
Summit Research Network LLC
🇺🇸
Seattle, Washington, United States
Clinical Neuroscience Solutions, Inc.
🇺🇸
Orlando, Florida, United States
Village Clinical Research Inc.
🇺🇸
New York, New York, United States
Meridien Research
🇺🇸
Tampa, Florida, United States
Northwest Behavioral Research Center
🇺🇸
Roswell, Georgia, United States
Finger Lakes Clinical Research
🇺🇸
Rochester, New York, United States
Keystone Clinical Studies, LLC
🇺🇸
Norristown, Pennsylvania, United States
Family Psychiatry of the Woodlands
🇺🇸
The Woodlands, Texas, United States
NoesisPharma,LLC
🇺🇸
Phoenix, Arizona, United States
IPS Research Company
🇺🇸
Oklahoma City, Oklahoma, United States
University ot California, San Francisco
🇺🇸
San Francisco, California, United States
Duke Child and Family Study Center
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Durham, North Carolina, United States
Paradigm Research Professionals
🇺🇸
Oklahoma City, Oklahoma, United States
Clinical Trials of Texas, Inc
🇺🇸
San Antonio, Texas, United States
Road Runner Research
🇺🇸
San Antonio, Texas, United States
NYU School of Medicine
🇺🇸
New York, New York, United States
North County Clinical Research
🇺🇸
Oceanside, California, United States
Triangle Neuropsychiatry
🇺🇸
Durham, North Carolina, United States
Pillar Clinical Research, LLC
🇺🇸
Dallas, Texas, United States
Carman Research
🇺🇸
Smyrna, Georgia, United States
MCB Clinical Research Centers, LLC
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Colorado Springs, Colorado, United States
Florida Clinical Research Center, LLC
🇺🇸
Maitland, Florida, United States
The Institute for Advanced Medical Research
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Alpharetta, Georgia, United States
Atlanta Center for Medical Research
🇺🇸
Atlanta, Georgia, United States
Alpine Clinic
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Lafayette, Indiana, United States
Lake Charles Clinical Trials
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Lake Charles, Louisiana, United States
Rochester Center for Behavioral Medicine
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Rochester Hills, Michigan, United States
Neurobehavioral Medicine Group
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Bloomfield Hills, Michigan, United States
Saint Charles Psychiatric Associates/Midwest Research Group
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Saint Charles, Missouri, United States
Midwest Research Group
🇺🇸
Saint Charles, Missouri, United States
Neuropsychiatric Associates
🇺🇸
Woodstock, Vermont, United States
Dean Foundation for Health, Research and Education
🇺🇸
Middleton, Wisconsin, United States
NeuroScience, Inc
🇺🇸
Herndon, Virginia, United States
CNS Clinical Research Group
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Coral Springs, Florida, United States
FutureSearch Trials of Dallas, LP
🇺🇸
Dallas, Texas, United States
Medical University of SC (MUSC)
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Charleston, South Carolina, United States
FutureSearch Clinical Trials, LP
🇺🇸
Austin, Texas, United States
Capstone Clinical Research, Inc.
🇺🇸
Libertyville, Illinois, United States