Clinical trial NCT02276209: Dasotraline Adult ADHD Study
Official title: 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)
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: 2014-10-28
Enrollment: 636
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 8 Weeks
Secondary outcomes:
measure: 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.
timeFrame: 8 Weeks
measure: 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.
timeFrame: 8 Weeks
measure: Change from baseline in Clinical Global Impression - Severity scale (CGI S) scale at Weeks 1, 2, 4, 6, and 8.
timeFrame: 8 Weeks
measure: Change from baseline in Sheehan Depression Scale (SDS) total score at Weeks 4 and 8.
timeFrame: 8 Weeks
measure: Change from baseline in Sheehan Depression Scale (SDS) domain scores: work/school, family life, social life at Weeks 4 and 8.
timeFrame: 8 Weeks
measure: 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.
timeFrame: 8 Weeks
measure: Change from baseline in ADHD Impact Module - Adult AIM A in global domain scores at Weeks 4 and 8.
timeFrame: 8 Weeks
measure: Time sensitive ADHD Symptom Scale (TASS) total score and subscale scores (Inattention and Hyperactive impulsive) at Weeks 3, 5, and 7.
timeFrame: 8 Weeks
measure: 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.
timeFrame: 8 Weeks
measure: Adult ADHD Medication Smoothness of Effect Scale (AMSES) score at Weeks 2, 4, 6, and 8.
timeFrame: 8 Weeks
measure: Change from baseline in Pittsburgh Sleep Quality Index (PSQI) global score and 7 component scores at Weeks 2, 4, and 8.
timeFrame: 8 Weeks
measure: The incidence of overall AEs, serious AEs (SAEs), and AEs (or SAEs) leading to discontinuations.
timeFrame: 8 Weeks
measure: Clinical laboratory evaluations (serum chemistry).
timeFrame: 8 Weeks
measure: Clinical laboratory evaluations ( lipid panel).
timeFrame: 8 Weeks
measure: Clinical laboratory evaluations (thyroid function panel).
timeFrame: 8 Weeks
measure: Clinical laboratory evaluations (hematology).
timeFrame: 8 Weeks
measure: Clinical laboratory evaluations (urinalysis).
timeFrame: 8 Weeks
measure: Clinical evaluations (vital signs).
timeFrame: 8 Weeks
measure: Clinical evaluations (orthostatic effects).
timeFrame: 8 Weeks
measure: Clinical evaluations (physical examinations).
timeFrame: 8 Weeks
measure: Clinical evaluations (body weight).
timeFrame: 8 Weeks
measure: Clinical evaluations (12 lead ECGs).
timeFrame: 8 Weeks
measure: Frequency and severity of suicidal ideation and suicidal behavior as assessed by the C SSRS.
timeFrame: 8 Weeks
measure: Drug Effects Questionnaire (DEQ) scores at Weeks 1, 2, 4, 6, and 8.
timeFrame: 8 Weeks
measure: Symptoms of withdrawal by Physician Withdrawal Checklist (PWC) scores at Week 8, 9, and 10.
timeFrame: 10 Weeks
measure: Symptoms of withdrawal by Study Medication Withdrawal Questionnaire (SMWQ) scores at Weeks 9 and 10.
timeFrame: 10 Weeks
measure: Symptoms of withdrawal by Hamilton Anxiety Rating Scale (HAM A) scores at Weeks 8, 9, and 10.
timeFrame: 10 Weeks
measure: Symptoms of withdrawal by Montgomery-Asberg Depression Rating Scale (MADRS) scores at Weeks 8, 9, and 10.
timeFrame: 10 Weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: NoesisPharma,LLC
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners
state: Arkansas
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: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Oceanside
country: United States
facility: North County Clinical Research
state: California
city: San Francisco
country: United States
facility: University ot California, San Francisco
state: California
city: Wildomar
country: United States
facility: Elite Clinical Trials, Inc.
state: California
city: Colorado Springs
country: United States
facility: MCB Clinical Research Centers, LLC
state: Colorado
city: Cromwell
country: United States
facility: ConnecticutClinicalResearch
state: Connecticut
city: Coral Springs
country: United States
facility: CNS Clinical Research Group
state: Florida
city: Fort Myers
country: United States
facility: Gulfcoast Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Maitland
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: Alpharetta
country: United States
facility: The 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: Roswell
country: United States
facility: Northwest Behavioral Research Center
state: Georgia
city: Smyrna
country: United States
facility: Carman Research
state: Georgia
city: Libertyville
country: United States
facility: Capstone Clinical Research, Inc.
state: Illinois
city: Lafayette
country: United States
facility: Alpine Clinic
state: Indiana
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
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: Bloomfield Hills
country: United States
facility: Neurobehavioral Medicine Group
state: Michigan
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine
state: Michigan
city: Saint Charles
country: United States
facility: Saint Charles Psychiatric Associates/Midwest Research Group
state: Missouri
city: Saint Charles
country: United States
facility: Midwest Research Group
state: Missouri
city: Lincoln
country: United States
facility: Premier Psychiatric Research Institute, LLC
state: Nebraska
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
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: Eastside Comprehensive Medical Center, LLC
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Durham
country: United States
facility: Duke Child and Family Study Center
state: North Carolina
city: Durham
country: United States
facility: Triangle Neuropsychiatry
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati, Department of Psychiatry
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Oklahoma City
country: United States
facility: Paradigm Research Professionals
state: Oklahoma
city: Portland
country: United States
facility: SummitResearchNetwork
state: Oregon
city: Portland
country: United States
facility: Oregon Center for Clinical Investigations, Inc.
state: Oregon
city: Salem
country: United States
facility: Oregon Center for Clinical Investigations, Inc.
state: Oregon
city: Norristown
country: United States
facility: Keystone Clinical Studies, LLC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of SC (MUSC)
state: South Carolina
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Austin
country: United States
facility: FutureSearch Clinical Trials, LP
state: Texas
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: Bayou City Research Corporation
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc
state: Texas
city: San Antonio
country: United States
facility: Road Runner Research
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 LLC
state: Washington
city: Middleton
country: United States
facility: Dean Foundation for Health, Research and Education
state: Wisconsin
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: SEP-289 Medical Director, MD
role: STUDY_DIRECTOR
References:
citation: Adler LA, Goldman R, Hopkins SC, Koblan KS, Kent J, Hsu J, Loebel A. Dasotraline in adults with attention deficit hyperactivity disorder: a placebo-controlled, fixed-dose trial. Int Clin Psychopharmacol. 2021 May 1;36(3):117-125. doi: 10.1097/YIC.0000000000000333.