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

ADHD Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02059642
• Other study ID #: AL012
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 30, 2014
• Last updated: March 3, 2015
• Start date: March 2014
• Est. completion date: September 2014

Study information

• Verified date: March 2014
• Source: Alcobra Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• ADHD
• Attention Deficit Disorder with Hyperactivity
• Attention-Deficit/Hyperactivity Disorder, Predominantly Inattentive Type
• Hyperkinesis

Intervention

Drug:
• MG01CI (1400 mg)
MG01CI (Metadoxine Immediate-release/Slow-release, Bilayer Caplet) 1400 mg administered orally once daily
• placebo
Placebo 1400 mg administered orally once daily

Locations

Country	Name	City	State
Israel	Neurocognitive unit Rambam MC	Haifa
Israel	ADHD unit Geha MC	Petach Tikva
United States	FutureResearch Trials	Austin	Texas
United States	Pediatric Psychopharmacology & Adult ADHD Program, Massachusetts General Hospital	Boston	Massachusetts
United States	FutureResearch Trials Dallas, LP	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Sarkis Clinical Trials	Gainesville	Florida
United States	NeuroScience, Inc. (NSI)	Herndon	Virginia
United States	Bayou City Research	Houston	Texas
United States	Center for Psychiatry and Behavioral Medicine	Las Vegas	Nevada
United States	University Kentucky Psychiatry	Lexington	Kentucky
United States	Capstone Clinical Research	Libertyville	Illinois
United States	Sequoia Behavioral Healthcare	Media	Pennsylvania
United States	Bioscience Research	Mount Kisco	New York
United States	Psychiatric Associates	Overland Park	Kansas
United States	Richard H Weisler, MD, PA	Raleigh	North Carolina
United States	Rochester Center For Behavioral Medicine	Rochester Hills	Michigan
United States	Miami Research	South Miami	Florida
United States	St. Charles Psychiatric Associates	St. Charles	Missouri
United States	Behavioral Medicine Center	Troy	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Alcobra Ltd.

Countries where clinical trial is conducted

United States,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total ADHD symptom score with adult prompts of the Conners Adult ADHD Rating Scale:O-SV in ADHD adults	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).	6 weeks	No
Secondary	Total ADHD symptom score with adult prompts of the CAARS Inv, in adults with predominantly inattentive ADHD (PI-ADHD)	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.	6 weeks	No
Secondary	Efficacy evaluation on the basis of improvement from baseline in CGI-I AND CGI-S	To evaluate the efficacy, of treatment with MG01CI 1400 mg .Efficacy will be assessed by change from Baseline in the total score	6 weeks	No
Secondary	Safety evaluation of treatment on the basis of adverse events number	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)	6 weeks	Yes
Secondary	Population PK (PopPK)	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.	6 weeks	Yes
Secondary	• Efficacy evaluation on the basis of improvement from baseline in ASRS-Self - expanded version	To evaluate the efficacy, of treatment with MG01CI 1400 mg .Efficacy will be assessed by change from Baseline in the total score	6 weeks	No
Secondary	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)	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	6 weeks	No
Secondary	Efficacy evaluation on the basis of improvement from baseline in BRIEF-A, Global Executive Composite, Behavioral Regulation Index and Metacognition Index	To evaluate the efficacy, of treatment with MG01CI 1400 mg .Efficacy will be assessed by change from Baseline in the total score	6 weeks	No