Clinical trial NCT02160262: Open-label Safety Study in Adults With ADHD
Official title: A Phase 3, 12-Month, Multicenter, Open-label, Flexibly-dosed, Safety Study of SEP 225289 in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Adult Attention Deficit Hyperactivity Disorder
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2014-06-10
Enrollment: 724
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the long-term safety and tolerability of SEP 225289 in adult subjects with Attention Deficit Hyperactivity Disorder (ADHD)

Detailed description: To evaluate the long-term safety and tolerability of SEP 225289 in adult subjects with ADHD by the incidence of adverse events (AEs; or serious AEs), AEs (or SAEs) leading to discontinuation

Eligibility criteria: Inclusion Criteria:

* Subject meets DSM 5 criteria for a primary diagnosis of ADHD (inattentive, hyperactive, or combined presentation) established by a comprehensive psychiatric evaluation that reviews DSM 5 criteria. Diagnosis is confirmed by CAADID Part 2 with checklist for DSM 5.
* Subject has an ADHD RS IV with adult prompts score of ≥ 22 at screening and baseline.
* Subject has agreed to participate by providing written informed consent and is willing and able to comply with the protocol, in the opinion of the investigator.
* Subject is 18 to 55 years old, inclusive, at the time of informed consent.
* Subject is male or a non-pregnant, non lactating female.
* Female subjects must have a negative serum pregnancy test; 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 throughout the study period.
* Subject has a negative breath alcohol test and a negative urine drug screen (UDS) for any illicit drug at screening.
* Subject is judged by the investigator to be suitable for participation in a 12 month clinical trial involving open-label dasotraline treatment.
* Subject can read well enough to understand the informed consent form and other subject materials.

Exclusion Criteria:

* Subject has a psychiatric disorder other than ADHD that has been the primary focus of treatment at any time during the 12 months prior to 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, or a personality disorder per DSM 5 criteria.
* Subject has a history of substance abuse or drug dependence (excluding nicotine and caffeine) within the 12 months prior to screening, as defined by the DSM 5 criteria.
* 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.
* Subject has a currently active medical condition (other than ADHD) that, in the opinion of the investigator, could interfere with the ability of the subject to participate in the study.
* Subject is currently taking or has taken within the previous 6 months an anticonvulsant medication (eg, phenytoin, carbamazepine, lamotrigine, valproic acid, etc); antipsychotic medication; or lithium (any lithium preparation or formulation).
* Subject is currently taking an alpha 2 adrenergic receptor agonist (including clonidine and guanfacine), or serotonin-norepinephrine reuptake inhibitor (SNRI; eg, venlafaxine), or dopamine-norepinephrine reuptake inhibitor (DNRI; eg, bupropion), or monoamine oxidase \[MAO\] inhibitor. Note: Subjects who discontinue these medications and wash-out from them for a minimum of 7 days prior to the first dose of study drug will be allowed to enroll in the study.
* Subject is currently undergoing Cognitive Behavioral Therapy (CBT).
* Subject has a Body Mass Index (BMI) less than 18 or greater than 35 kg/m2 (see Appendix V).
* 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 1 year prior to 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 for the reference lab.
* 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 serum chemistry results show an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value ≥ 2 times the upper limit of normal (ULN), or a blood urea nitrogen (BUN) value ≥ 1.5 times the ULN for the reference laboratory.
* 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.
* Subject has a history of allergic reaction or has a known or suspected sensitivity to any substance that is contained in the study drug formulation.
* Subject has previously been randomized in a clinical trial of dasotraline.
* Subject is likely to be noncompliant in the investigator's opinion.
* Subject is an investigational site staff member or the relative of an investigational site staff member.

Primary outcomes:
measure: The incidence of AEs (or SAEs), and AEs (or SAEs) leading to discontinuation.
timeFrame: 12 months
Secondary outcomes:
measure: Clinical evaluations (vital signs, physical examination, body weight, and 12 lead ECG)
timeFrame: 12 Months
measure: Clinical laboratory evaluations (serum chemistry, hematology, lipid panel, thyroid panel, and urinalysis)
timeFrame: 12 months
measure: Drug Effects Questionnaire (DEQ)
timeFrame: 12 months
measure: Frequency and severity of suicidal ideation and suicidal behavior using the Columbia - Suicide Severity Rating Scale (C SSRS)
timeFrame: 12 months
measure: Change from baseline in ADHD RS IV with adult prompts total score
timeFrame: 12 months
measure: Change from baseline in Clinical Global Impression - Severity (CGI S) score
timeFrame: 12 months
measure: Change from baseline in the ADHD RS IV with adult prompts inattentiveness and hyperactivity-impulsivity subscale scores
timeFrame: 12 months
measure: Change from baseline in AIM A in global domain scores (Performance and Daily Functioning, Impact of Symptoms: Daily Interference, Impact of Symptoms: Bother/Concern, Relationships/Communication, Living with ADHD, and General Well-being)
timeFrame: 12 months
measure: Change from baseline in Sheehan Disability Scale (SDS) total score
timeFrame: 12 months
measure: Change from baseline in Sheehan Disability Scale (SDS) domain scores: work/school, family life, social life
timeFrame: 12 months
measure: Change from baseline in Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF®) A Global Executive Composite raw score and Behavioral Regulation Index (BRI) raw score and Metacognition Index (MI) raw score.
timeFrame: 12 months
measure: Change from baseline in Pittsburgh Sleep Quality Index (PSQI) global score and 7 component scores.
timeFrame: 12 months
measure: Change from baseline in BRIEF-A Global Executive Composite T-score and BRI T-score and MI T-score.
timeFrame: 12 months
measure: Symptoms of withdrawal using Physician Withdrawal Checklist (PWC) scores, Study Medication Withdrawal Questionnaire (SMWQ) scores, Montgomery-Asberg Depression Rating Scale (MADRS) scores, Hamilton Anxiety Rating Scale (HAM-A) scores
timeFrame: 12 months
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Southern California Research LLC
state: California
city: Encino
country: United States
facility: Pharmacology Research Institute
state: California
city: Escondido
country: United States
facility: Synergy Clinical Research of Escondido
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Oceanside
country: United States
facility: Excell Research, Inc
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Colorado Springs
country: United States
facility: MCB Clinical Research Centers, LLC
state: Colorado
city: Bradenton
country: United States
facility: Florida Clinical Research Center LLC
state: Florida
city: Fort Myers
country: United States
facility: Gulfcoast Clinical Research
state: Florida
city: Hollywood
country: United States
facility: Broward Research Group, Inc.
state: Florida
city: Jacksonville Beach
country: United States
facility: Geroge M. Joseph MD, PA
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Leesburg
country: United States
facility: Compass Research North, LLC
state: Florida
city: Maitland
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Melbourne
country: United States
facility: Acumentality
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: Alpharetta
country: United States
facility: Institute for Advanced Medical Research
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta, LLC
state: Georgia
city: Smyrna
country: United States
facility: Carman Research
state: Georgia
city: Indianapolis
country: United States
facility: Goldpoint Clinical Research
state: Indiana
city: Lafayette
country: United States
facility: Alpine Clinic
state: Indiana
city: Overland Park
country: United States
facility: Psychiatric Associates
state: Kansas
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials LLC
state: Louisiana
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine
state: Michigan
city: O'Fallon
country: United States
facility: Psychiatric Care & Research Center
state: Missouri
city: Saint Charles
country: United States
facility: Midwest Research Group
state: Missouri
city: Lincoln
country: United States
facility: Premeir Psychiatric Research Institute, LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine, Inc.
state: Nevada
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
city: Mount Kisco
country: United States
facility: Bioscience Research
state: New York
city: New York
country: United States
facility: Village Clinical Research Inc.
state: New York
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: New York
country: United States
facility: Medical & Behavioral Health Research
state: New York
city: New York
country: United States
facility: The Medical Research Network, LLC
state: New York
city: New York
country: United States
facility: Fieve Clinical Research
state: New York
city: Staten Island
country: United States
facility: Woodhull Medical & Mental Health Center
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Canton
country: United States
facility: Neuro-Behavioral Clinical Research
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Portland
country: United States
facility: Summit Research Network
state: Oregon
city: Portland
country: United States
facility: Oregon Center for Clinical Investigations, Inc.
state: Oregon
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Norristown
country: United States
facility: Keystone Clinical Studies, LLC
state: Pennsylvania
city: West Chester
country: United States
facility: Sleep Diagnosists and Treatment Centers
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions
state: Tennessee
city: Memphis
country: United States
facility: Research Strategies of Memphis, LLC
state: Tennessee
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, LP
state: Texas
city: Dallas
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: Houston
country: United States
facility: Houston Clinical Trials, LLC
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of the Woodlands
state: Texas
city: Woodstock
country: United States
facility: Neuropsychiatric Associates
state: Vermont
city: Herndon
country: United States
facility: NeuroScience, Inc
state: Virginia
city: Seattle
country: United States
facility: Summit Research Network (Seattle) LLC
state: Washington
city: Middleton
country: United States
facility: Dean Foundation
state: Wisconsin
city: Middleton
country: United States
facility: Eastside Therapeutic Resource
state: Wisconsin
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: SEP289 Medical Director
role: STUDY_DIRECTOR
References: