Clinical trial NCT02059642: A 6 Week Study of MG01CI 1400 mg Compared With Placebo in Adults With ADHD ( Attention Deficit/Hyperactivity )
Official title: A 6-week Randomized, Multicenter, Double-blind, Parallel, Fixed-dose Study of MG01CI (Metadoxine Immediate-release/Slow-release, Bilayer Caplet) 1400 mg Compared With Placebo in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: ADHD
Attention-Deficit/Hyperactivity Disorder, Predominantly Inattentive Type
Lead sponsor: Alcobra Ltd.
Sponsor class: INDUSTRY
First posted: 2014-02-11
Enrollment: 300
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 study is a multisite, randomized, double-blind, placebo-controlled, phase 2/3 study of MG01CI (1400 mg daily) for 6 weeks compared with placebo in a 1:1 ratio of 300 adults with ADHD.

Detailed description: This study is a multisite, randomized, double-blind, placebo-controlled, phase 2/3 study of MG01CI (1400 mg once daily) for 6 weeks compared with placebo in a 1:1 ratio of 300 adults with ADHD. The study comprises a Screening Visit at which initial assessment will be made and then a Washout Period during which prospective subjects must discontinue ADHD medication for 14 days (for psychotropic medications other than fluoxetine) or for 28 days (for fluoxetine) before randomization into the study. The Washout Period is 14 days, but may be extended to 28 days for a fluoxetine washout. Subjects requiring either a 14-day or a 28-day Washout Period will have an Interim Visit (off drug) on or about Day -8 (Day -10 to Day -3) for CAARS-Inv assessment after the Washout Period. The Baseline CAARS Inv assessment will be conducted on Day 0. If there is a ≥25% change in the CAARS-Inv results between the Interim Visit (off drug) assessment and the Baseline assessment, or if the subject does not return for the Baseline CAARS-Inv assessment, the subject will not be randomized. For subjects not needing washout, if there is a ≥25% change in the CAARS-Inv results between the Screening Visit assessment and the Baseline assessment, or if the subject does not return for the Baseline CAARS-Inv assessment, the subject will not be randomized. Following the Washout Period for those requiring a washout, or following the Screening Visit for those subjects who do not require a washout, eligible subjects will undergo baseline assessments and be randomized on Day 0 to MG01CI 1400 mg or to matching placebo and begin the Double-blind Treatment Period. The Double-blind Treatment Period will be 6 weeks in duration. There will be a 2-week Follow-up Period after the last dose of study treatment or early termination.

Eligibility criteria: Inclusion Criteria:

* Subject is a man or a non-pregnant, non-lactating woman 18 to 55 years of age, inclusive, at the Screening Visit.
* Subject has a diagnosis of ADHD based on criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and DSM5.
* Subject has ADHD with at least moderate clinical severity (Clinical Global Impression-Severity \[CGI-S\]) score of 4 or greater).
* Subject has a score on the total ADHD symptom score with adult prompts of the CAARS-Inv of at least 22.
* Female subjects of childbearing potential must agree to use an effective contraceptive throughout the study
* Subject is able to attend the clinic regularly and reliably.
* Subject is able to swallow tablets and capsules.
* Subject is able to understand, read, write, and speak English fluently to complete the study-related materials (or Hebrew for Israeli subjects).
* Subject is able to understand and sign an informed consent form to participate in the study.

Exclusion Criteria:

* Subject did not respond in the past to 2 adequate trials of stimulant treatments or 1 adequate trial of atomoxetine treatment (in the investigator's judgment).
* Subject has any psychiatric condition clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation as determined by the investigator .
* Subject has a known or suspected human immune deficiency virus-positive status or has diseases such as acquired immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis.
* Subject has a history of an allergy or sensitivity to B-complex vitamins.
* Subject has a history of intellectual disability or a history or suspicion of autism spectrum disorder.
* Subject has a current Axis I diagnosis (other than ADHD) according to the Structured Clinical Interview for DSM IV Axis I Disorders (SCID) or has a lifetime history of bipolar disorder or psychosis.
* Subject has used mega-dose vitamin B6/pyridoxine during the 28 days before the Screening Visit.
* Subject has used high-dose supplements of omega-3 fatty acids ≥ 500 mg on at least 1 day or folic acid supplements during the 2 weeks before the Screening Visit.
* Subject has used an investigational medication/treatment in the 30 days before the Screening Visit
* Subject has used any medication or food supplement that the investigator or the medical monitor considers unacceptable during the 14-day period before randomization.
* Subject has a current drug or alcohol dependence or substance abuse disorder according to DSM-IV. Subject should also agree to keep their caffeine intake consistent and refrain from consuming ≥300 mg per day of caffeine (no more than three 8-ounce servings of coffee) during the study.
* Subject has suicidality, defined as active ideation, an intent or plan, or any significant lifetime suicidal behavior. Subjects exhibiting history (within previous 12 months) of non-suicidal self-injurious behavior will be excluded.
* Subject has taken any prescription or non-prescription ADHD medications during the 14 days (for all psychotropic medications other than fluoxetine) or 28 days (for fluoxetine) before the randomization visit.
* Subject is significantly visually impaired to an extent that is not able to be corrected by prescription glasses or contact lenses
* Subject is related to the sponsor, investigator, or study staff.
* Subject has any condition that, in the principal investigator's opinion, would place the subject at risk or influence the conduct of the study or interpretation of results,
* Subject cannot fully comprehend the implications of the protocol, cannot comply with its requirements, or is incapable of following the study schedule for any reason.
* Subject is pregnant, lactating, or using an inadequate contraceptive method.
* If there is a ≥25% change in the CAARS-Inv results between the Interim visit (off drug) assessment and the Baseline assessment, or if the subject does not return for the Baseline CAARS-Inv assessment, the subject will not be randomized. For subjects not needing washout, if there is a ≥25% change in the CAARS-Inv results between the Screening Visit assessment and the Baseline assessment, or if the subject does not return for the Baseline CAARS-Inv assessment, the subject will not be randomized.

Primary outcomes:
measure: Change in Total ADHD Symptom Score With Adult Prompts of the Conners Adult ADHD Rating Scale:O-SV in ADHD Adults From Baseline to 6 Weeks
timeFrame: baseline, 6 weeks
Secondary outcomes:
measure: Safety Evaluation of Treatment on the Basis of Percentage of Participants With Treatment Emergent Adverse Events
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: South Miami
country: United States
facility: Miami Research
state: Florida
city: Libertyville
country: United States
facility: Capstone Clinical Research
state: Illinois
city: Overland Park
country: United States
facility: Psychiatric Associates
state: Kansas
city: Lexington
country: United States
facility: University Kentucky Psychiatry
state: Kentucky
city: Boston
country: United States
facility: Pediatric Psychopharmacology & Adult ADHD Program, Massachusetts General Hospital
state: Massachusetts
city: Rochester Hills
country: United States
facility: Rochester Center For Behavioral Medicine
state: Michigan
city: Troy
country: United States
facility: Behavioral Medicine Center
state: Michigan
city: St. Charles
country: United States
facility: St. Charles Psychiatric Associates
state: Missouri
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine
state: Nevada
city: Mount Kisco
country: United States
facility: Bioscience Research
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Raleigh
country: United States
facility: Richard H Weisler, MD, PA
state: North Carolina
city: Media
country: United States
facility: Sequoia Behavioral Healthcare
state: Pennsylvania
city: Austin
country: United States
facility: FutureResearch Trials
state: Texas
city: Dallas
country: United States
facility: FutureResearch Trials Dallas, LP
state: Texas
city: Houston
country: United States
facility: Bayou City Research
state: Texas
city: Herndon
country: United States
facility: NeuroScience, Inc. (NSI)
state: Virginia
city: Haifa
country: Israel
facility: Neurocognitive unit Rambam MC
city: Petach Tikva
country: Israel
facility: ADHD unit Geha MC
Study officials:
affiliation: University of North Carolina, Duke University
name: Richard Weisler, MD
role: PRINCIPAL_INVESTIGATOR
References: