Clinical trial NCT01692782: Adult Attention Deficit Hyperactivity Disorder
Official title: A Randomized, Double Blind, Parallel Group, Multicenter Efficacy and Safety Study of SEP-225289 Versus Placebo in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Attention Deficit Hyperactivity Disorder
Keywords: ADHD
Attention deficit hyperactivity disorder
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2012-09-25
Enrollment: 341
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: A Phase 2 study of SEP-225289 in adults with attention deficit hyperactivity disorder (ADHD).

Detailed description: This is a Phase 2, randomized, double-blind, parallel-group, multicenter, outpatient study evaluating the efficacy and safety of SEP 225289 in adults with ADHD using 2 oral dosages (4 or 8 mg SEP 225289 once daily \[QD\]) versus placebo over a 4 week treatment period.

Eligibility criteria: Inclusion Criteria:

* Subject meets Diagnostic and Statistical Manual of Mental Disorders Fourth Edition; Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD (inattentive, hyperactive, or combined subtype) established by a comprehensive psychiatric evaluation that reviews DSM-IV-TR criteria. Diagnosis is confirmed by Conners' Adult ADHD Diagnostic Interview (CAADID) Part 2.
* Subject currently taking medication (stimulant or nonstimulant) for the control of ADHD symptoms has an ADHD RS-IV score of ≥ 22 at screening.
* Subject currently not taking any medication for the purpose of controlling ADHD symptoms has an ADHD RS-IV score of ≥ 26 at screening.
* Subject has a CGI-S score of ≥ 4 at screening.
* Subject has a lifetime history of treatment with at least one medication for ADHD (stimulant or nonstimulant). Subjects may be either medicated or unmedicated for ADHD at the time of screening (all ADHD medications must be washed out during screening).
* Subject has a negative breath alcohol test and a negative urine drug screen (UDS) for any illicit drug at screening, unless a false positive is suspected, in which case the UDS will be repeated. If the subject has a positive drug screen for ADHD medications (ie, methylphenidate or amphetamine) at screening; the subject must have a negative UDS after a washout period at least 3 days prior to baseline.
* Subject is male or a non-pregnant, non-lactating female.
* Female subjects must have a negative serum pregnancy test at screening; women 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 child-bearing potential must agree to use an effective and medically acceptable form of birth control throughout the study period and for one month (30 days) after study completion. Medically acceptable and effective contraceptives include abstinence, prescription hormonal contraceptives (oral, patch, vaginal ring, implant, or injection), diaphragm with spermicide, intrauterine device (IUD), condom with spermicide, surgical sterilization, or vasectomy. For male subjects adequate contraception is defined as abstinence or continuous use of 2 barrier methods of contraception (eg, spermicidal condom).
* Subject is 18 to 55 years old, inclusive, at the time of informed consent. 11. Subject can read well enough to understand the informed consent form and other subject materials.

Exclusion Criteria:

* Subject has a DSM-IV-TR diagnosis of ADHD not otherwise specified.
* Subject is receiving adequate benefit from current ADHD medication in the opinion of the investigator.
* Subject has an Axis I 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, bipolar II, and bipolar not otherwise specified \[NOS\]), schizophrenia, schizoaffective disorder, or any other psychotic disorder.
* Subject has a history of drug dependence or substance abuse (excluding nicotine and caffeine) within the 12 months prior to screening, as defined by the DSM-IV-TR criteria.
* Subject has a current Axis II disorder per DSM-IV-TR 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 an antidepressant medication (eg, bupropion, selective serotonin reuptake inhibitor \[SSRI\]/ serotonin norepinephrine reuptake inhibitor \[SNRI\], monoamine oxidase \[MAO\] blocker, tricyclic, etc) or St. John's Wort.
* 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).
* Subject has a Body Mass Index (BMI) less than 18 or greater than 35 kg/m2 (refer to 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 2 years prior to the screening period.
* Subject has history of positive test for Hepatitis B surface antigen or Hepatitis C antibody. Note: Subjects with a history of a positive test for Hepatitis B surface antigen or Hepatitis C antibody may be enrolled in the study if they have liver function test results at screening within the normal range.
* 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 in consultation with the medical monitor 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.
* The subject's screening hematology 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 lab.
* Subject who is currently participating or has participated in a clinical trial within the last 180 days or who participated in more than 2 clinical trials within the past year. This includes studies using marketed compounds or devices.
* Subject is at high risk of non-compliance in the investigator's opinion.

Primary outcomes:
measure: Change From Baseline at Week 4 in ADHD Symptoms Measured With the ADHD Rating Scale Version IV With Adult Prompts (ADHD RS IV)
timeFrame: 4 Weeks
Secondary outcomes:
measure: Change From Baseline in ADHD Symptoms Measured With the ADHD RS IV at Weeks 1, 2, 3.
timeFrame: Weeks 1, 2, 3
measure: Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI S) at Weeks 1, 2, 3, 4.
timeFrame: Weeks 1, 2, 3, 4
measure: Change From Baseline in the Inattentiveness and Hyperactivity Subscales of the ADHD RS IV at Weeks 1, 2, 3, 4
timeFrame: Weeks 1, 2, 3, 4
measure: The Number of Responders at Weeks 1, 2, 3, 4. A Responder is Defined as a Subject With a ≥ 30% Improvement in ADHD Symptoms Compared With Baseline as Measured by the ADHD RS IV.
timeFrame: Weeks 1, 2, 3, 4
measure: Change From Baseline in the Wender-Reimher Adult Attention Deficit Disorder Scale (WRAADDS) as Measured at Weeks 1, 2, 3, 4.
timeFrame: Weeks 1, 2, 3, 4
Other outcomes:
Locations:
city: Encino
country: United States
facility: Pharmacology Research Institute
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network Inc
state: California
city: Irvine
country: United States
facility: University of California at Irvine
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Institute
state: California
city: Oceanside
country: United States
facility: Excell Research, Inc
state: California
city: Santa Ana
country: United States
facility: Neuropsychiatric Research Center of Orange County
state: California
city: Bradenton
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions Inc.
state: Florida
city: Maitland
country: United States
facility: Florida Research Center
state: Florida
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Oakland Park
country: United States
facility: Research Centers of America, LLC
state: Florida
city: Sanford
country: United States
facility: Medical Research Group of Central Florida
state: Florida
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: Indianapolis
country: United States
facility: Goldpoint Clinical Research
state: Indiana
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Indiana
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Health
state: Michigan
city: St. Charles
country: United States
facility: Midwest Research Group
state: Missouri
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
city: Brooklyn
country: United States
facility: Brooklyn Medical Institutes, LLC
state: New York
city: Durham
country: United States
facility: Duke Child and Family Study Center
state: North Carolina
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
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: Philadelphia
country: United States
facility: CRI Lifetree
state: Pennsylvania
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions
state: Tennessee
city: Austine
country: United States
facility: Future Search Clinical Trials, LP
state: Texas
city: Herndon
country: United States
facility: NeuroScience, Inc
state: Virginia
city: Kirkland
country: United States
facility: Eastside Therapeutic Resource
state: Washington
city: Seattle
country: United States
facility: Summit Research Network, LLC-Seattle
state: Washington
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: CNS Medical Director, MD
role: STUDY_DIRECTOR
References:
citation: Hopkins SC, Sunkaraneni S, Skende E, Hing J, Passarell JA, Loebel A, Koblan KS. Pharmacokinetics and Exposure-Response Relationships of Dasotraline in the Treatment of Attention-Deficit/Hyperactivity Disorder in Adults. Clin Drug Investig. 2016 Feb;36(2):137-46. doi: 10.1007/s40261-015-0358-7.