Study Comparing Two Doses of MG01CI and Placebo in Adults With Predominantly Inattentive Attention Deficit Hyperactivity Disorder

Study Overview
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Brief Summary
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study objectives are to compare the efficacy, safety and tolerability of two doses of MG01CI (1400 mg and 700 mg) to Placebo for the treatment of symptoms in adults diagnosed with PI-ADHD. subjects will be randomly assigned in a 1:1:1 ratio to one of three treatment sequences as follows: week 1:1400 mg, week 2:700 mg, week 3:placebo week 1:700 mg,week 2: placebo,week 3:1400 mg week 1: placebo, week2:1400 mg, week 3 700 mg The study will consist of three periods: a screening period of up to one week, a 3-week double-blind treatment period, and a one-week safety follow-up period.

Detailed Description
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The purpose of this dose finding study is to compare two doses of MG01CI (1400 mg and 700 mg) to Placebo, in adult subjects with PI-ADHD. A crossover study design will allow evaluation of safety/tolerability and efficacy using validated computerized tests. subjects will be randomly assigned in a 1:1:1 ratio to one of three treatment sequences as follows: week 1:1400 mg, week 2:700 mg, week 3:placebo week 1:700 mg,week 2: placebo,week 3:1400 mg week 1: placebo, week2:1400 mg, week 3 700 mg Overview of Study Visits Screening Period: Visit 1 - Screening/Baseline Visit (up to 7 days prior to dosing) Treatment Period: Visit 2 - Day 0 (Randomization Visit) Visit 3 - Day 7 ± 3 days Visit 4 - Day 14 ± 3 days Visit 5 - Day 21 ± 3 days Follow-up period: Visit 6 - Day 28 ± 3 days Study duration for each subject will be up to 35 days .

Official Title
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Randomized, Double-blind, Single-center, Dose-finding Study Designed to Compare Two Doses of MG01CI (Metadoxine Extended Release) and Placebo in Adults With Predominantly Inattentive Attention Deficit Hyperactivity Disorder

Conditions
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ADHD Predominantly Inattentive Type

Intervention / Treatment
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* Drug: Metadoxine (MG01CI)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult men and women, 18 to 55 years old Diagnosed with predominantly inattentive ADHD based on DSM-IV criteria for ADHD as assessed by the Adult ADHD Clinician Diagnostic Scale (ACDS V1.2); Clinical severity of at least a moderate level (Clinical Global Impression score of 4 or above) TOVA ADHD score of -1.8 or below at Screening /Baseline Women with childbearing potential must agree to use effective contraceptive and have negative urine pregnancy test at screening visit Able to attend the clinic regularly and reliably Able to swallow tablets/capsules Able to understand, read, write and speak Hebrew fluently to complete study related materials Able to understand and sign written informed consent to participate in the study Exclusion Criteria: Subjects with ADHD not otherwise specified (NOS) diagnosis Subjects with combined type or predominantly hyperactive impulsive ADHD diagnoses Subjects with current Axis I diagnosis on SCID Subjects with lifetime bipolar or psychosis Subjects in treatment for Axis I disorders, even if the disorder is remitted Subjects who were non-responders to at least two adequately administered ADHD treatments Subjects with any medical or psychiatric condition common diseases such as hypertension, type 2 diabetes mellitus, hyperlipidemia, etc. are allowed per the Investigator's judgment, as long as they are stable and controlled by medical therapy that is constant for at least 8 weeks prior to randomization and throughout the study Any prescription or non-prescription ADHD medications during the 14 days (for stimulants) or 28 days (for non-stimulants and other psychotropics) prior to the screening visit Known or suspected HIV-positive or with advanced diseases such as AIDS, Hepatitis C, Hepatitis B or tuberculosis History of allergy or sensitivity to B complex vitamins History or suspicion of PDD, NLD or other psychotic conditions Use of Vitamin B throughout the study (either alone or in any multi-vitamin) Use of ADHD medications throughout the study Use of any psychotropic medications throughout the study Use of investigational medication/treatment in the past 30 days prior to the screening visit Use of any medication or food supplement unless cleared by the medical monitor during the 14-day period before randomization Current (or history within the last 6 months) of drug dependence or substance abuse disorder according to DSM-IV-TR criteria (excluding nicotine). Subjects should also agree to refrain from significantly changing consumption of caffeine during the study. Suicidality, defined as active ideation, intent or plan, or any lifetime attempt (CSSRS) Subjects who cannot complete any study instruments or questionnaires Any relation to the Sponsor, Investigator or study staff Any condition, which in the opinion of the Principal Investigator would place the subject at risk or influence the conduct of the study or interpretation of results, including (but not limited to) abnormally low intellectual capacity. Subjects who cannot fully comprehend the implications of the protocol or comply with its requirements or are capable to follow the study schedule for any reason Women of childbearing potential must test negative for pregnancy at the time of enrollment based on a serum pregnancy test and agree to use a reliable method of birth control (e.g., oral contraceptives or Norplant®; a reliable barrier method of birth control [diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam]; intrauterine devices; partner with vasectomy; or abstinence) during the study. Note that this inclusion criterion applies only to females of childbearing potential. Females of childbearing potential are defined as women not surgically sterilized and between menarche and 2 years post-menopause

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metadoxine (MG01CI) 1400 mg<br>single dose of Metadoxine (MG01CI) 1400 mg | Drug: Metadoxine (MG01CI)<br>* MG01CI is an orally administered extended release formulation of metadoxine. Doses: 1400 mg and 700 mg and Placebo<br>* Other names: metadoxil;|
| Active Comparator: Metadoxine (MG01CI) 700 mg<br>Single dose of Metadoxine (MG01CI) 700 mg | Drug: Metadoxine (MG01CI)<br>* MG01CI is an orally administered extended release formulation of metadoxine. Doses: 1400 mg and 700 mg and Placebo<br>* Other names: metadoxil;|
| Placebo Comparator: Placebo<br>Single dose of Placebo | Drug: Placebo<br>* Placebo tablets will be similar in appearance (color and size) to the investigational product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TOVA ADHD score from Screening/Baseline to 4 hours post-dose; | TOVA® is a computerized test that provides information about an individual's sustained attention, speed and consistency of responding, and behavioral self-regulation and executive functioning | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CANTAB sub-scores from baseline (Visit 2) to 4 hours post-dose; | The CANTAB is a computerized test assessing the key cognitive deficits present in ADHD. Sub-scores will include spatial working memory (SWM), stop signal task (SST), rapid visual information processing (RVP), and reaction time (RTI). | 4 weeks | 
| Change in TOVA sub-scores from Screening/Baseline to 4 hours post-dose |  | 4 weeks | 
| Number of participants who withdrew early from the study due to AE |  | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD , Inattention