A 6 Week Randomized Study of MG01CI 1400 mg Compared With Placebo in Adults With ADHD (Adults With Attention Deficit/Hyperactivity )

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Alcobra Ltd.
ClinicalTrials.gov Identifier:
NCT02059642
First received: January 30, 2014
Last updated: July 14, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
ADHD
Predominantly Inattentive ADHD (PI-ADHD)
Drug: MG01CI (1400 mg)
Drug: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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)

Further study details as provided by Alcobra Ltd.:

Primary Outcome Measures:
  • Total ADHD symptom score with adult prompts of the Conners Adult ADHD Rating Scale:O-SV in ADHD adults [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    To evaluate the efficacy of MG01CI (Metadoxine immediate-release/slow-release, bilayer caplet) 1400 mg daily compared with placebo in the treatment of ADHD in adults as measured by the total ADHD symptom score with adult prompts of the Conners Adult ADHD Rating Scale:O-SV observer) (CAARS-Inv).


Secondary Outcome Measures:
  • Total ADHD symptom score with adult prompts of the CAARS Inv, in adults with predominantly inattentive ADHD (PI-ADHD) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    To evaluate the efficacy of MG01CI (Metadoxine immediate-release/slow-release, bilayer caplet) 1400 mg daily compared with placebo in the treatment of adults with predominantly inattentive ADHD (PI-ADHD) as measured by the total ADHD symptom score with adult prompts of the CAARS Inv.

  • Efficacy evaluation on the basis of improvement from baseline in CGI-I AND CGI-S [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    To evaluate the efficacy, of treatment with MG01CI 1400 mg .Efficacy will be assessed by change from Baseline in the total score

  • Safety evaluation of treatment on the basis of adverse events number [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Safety assessments will be based on changes from Baseline of clinical AEs reported by the subject or observed by the Investigator and concomitant medication use, treatment adherence (eg, dropouts due to AEs)

  • Population PK (PopPK) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Population PK (PopPK) modeling and evaluation of clearance (CL) and volume of distribution (Vd) will be based on sparse plasma sample collections from a subset of subjects PK samples collected before dose administration will be used to estimate the baseline concentrations. Baseline concentrations of pyridoxine and L-PGA will be estimated for each subject and the baseline concentrations will be subtracted from the concentrations before PopPK analysis.

  • • Efficacy evaluation on the basis of improvement from baseline in ASRS-Self - expanded version [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    To evaluate the efficacy, of treatment with MG01CI 1400 mg .Efficacy will be assessed by change from Baseline in the total score

  • Efficacy evaluation on the basis of improvement from baseline in AAQoL total score and 4 sub-scores (Life Productivity, Psychological Health, Relationships and Life outlook) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    To evaluate the efficacy, of treatment with MG01CI 1400 mg .Efficacy will be assessed by change from Baseline in the sub score and total score

  • Efficacy evaluation on the basis of improvement from baseline in BRIEF-A, Global Executive Composite, Behavioral Regulation Index and Metacognition Index [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    To evaluate the efficacy, of treatment with MG01CI 1400 mg .Efficacy will be assessed by change from Baseline in the total score


Estimated Enrollment: 300
Study Start Date: March 2014
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo tablet identical in appearance to study investigational product Route, frequency: Administered orally once daily
Drug: placebo
Placebo 1400 mg administered orally once daily
Experimental: MG01CI (1400 mg)
MG01CI (Metadoxine Immediate-release/Slow-release, Bilayer Caplet) Dose, route, and frequency: 1400 mg administered orally once daily
Drug: MG01CI (1400 mg)
MG01CI (Metadoxine Immediate-release/Slow-release, Bilayer Caplet) 1400 mg administered orally once daily
Other Name: Metadoxine Immediate-release/Slow-release, Bilayer Caplet

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02059642

Locations
United States, Florida
Sarkis Clinical Trials
Gainesville, Florida, United States, 32607
Miami Research
South Miami, Florida, United States, 33173
United States, Illinois
Capstone Clinical Research
Libertyville, Illinois, United States, 60048
United States, Kansas
Psychiatric Associates
Overland Park, Kansas, United States, 66211
United States, Kentucky
University Kentucky Psychiatry
Lexington, Kentucky, United States, 40509
United States, Massachusetts
Pediatric Psychopharmacology & Adult ADHD Program, Massachusetts General Hospital
Boston, Massachusetts, United States, 21144
United States, Michigan
Rochester Center For Behavioral Medicine
Rochester Hills, Michigan, United States, 48307
Behavioral Medicine Center
Troy, Michigan, United States, 48083
United States, Missouri
St. Charles Psychiatric Associates
St. Charles, Missouri, United States, 63301
United States, Nevada
Center for Psychiatry and Behavioral Medicine
Las Vegas, Nevada, United States, 89128
United States, New York
Bioscience Research
Mount Kisco, New York, United States, 10549
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
Richard H Weisler, MD, PA
Raleigh, North Carolina, United States, 27609
United States, Pennsylvania
Sequoia Behavioral Healthcare
Media, Pennsylvania, United States, 19063
United States, Texas
FutureResearch Trials
Austin, Texas, United States, 78731
FutureResearch Trials Dallas, LP
Dallas, Texas, United States, 75231
Bayou City Research
Houston, Texas, United States, 77007
United States, Virginia
NeuroScience, Inc. (NSI)
Herndon, Virginia, United States, 20170
Israel
Neurocognitive unit Rambam MC
Haifa, Israel
ADHD unit Geha MC
Petach Tikva, Israel
Sponsors and Collaborators
Alcobra Ltd.
Investigators
Principal Investigator: Richard Weisler, MD University of North Carolina, Duke University
  More Information

No publications provided

Responsible Party: Alcobra Ltd.
ClinicalTrials.gov Identifier: NCT02059642     History of Changes
Other Study ID Numbers: AL012
Study First Received: January 30, 2014
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration
Israel: Ministry of Health

Additional relevant MeSH terms:
Hyperkinesis
Attention Deficit Disorder with Hyperactivity
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Metadoxine
Alcohol Deterrents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014