Clinical Efficacy & Safety, of Metadoxine (MG01CI) Extended Release in Attention-Deficit Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy, safety and tolerability of metadoxine (MG01CI) extended release formulation for the treatment of adults diagnosed with ADHD

Detailed Description
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This will be a randomized, double-blind, placebo-controlled, parallel-group, multicenter study in adult subjects with ADHD. Eligible subjects will be randomly assigned in a 1:1 ratio to one of two treatment groups, 1400 mg Metadoxine (MG01CI) and Placebo. The study will consist of three periods: a screening period of up to 2 weeks, a 6-week double-blind treatment period, and a 2-week safety follow-up period. The total duration of subject participation will be  10 weeks. Overview of Study Visits Screening Period: Visit 1 - Screening/Baseline Visit (up to 14 days prior to dosing) Treatment Period: Visit 2 - Day 0 (Randomization Visit) Visit 3 - Day 7 ± 2 days Visit 4 - Day 14 ± 2 days Visit 5 - Day 28 ± 2 days Visit 6 - Day 42 ± 2 days Follow-up period: Visit 7 - Day 56 ± 3 days

Official Title
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Randomized, Double-blind, Placebo-controlled, Multi-center Study Designed to Evaluate the Efficacy, Safety and Tolerability of Metadoxine Extended Release in Adults With Attention Deficit Hyperactive Disorder

Conditions
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ADHD

Intervention / Treatment
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* Drug: Metadoxine (MG01CI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males and females, 18 to 50 years old, inclusive, at screening visit Diagnosed with ADHD based on DSM-IV criteria for ADHD as assessed by the Adult ADHD Clinician Diagnostic Scale (ACDS V1.2) SCID clinical interview Clinical severity of at least a moderate level (Clinical Global Impression score of 4 or above) Female subjects 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 who were non-responder to at least two ADHD treatments Subjects with any medical or psychiatric condition (e.g. schizophrenia, personality disorder as diagnosed by DSM-IV) or clinical significant or unstable medical or surgical condition that may preclude safe and complete study participation as determined by medical history, physical examination, neurological exam, laboratory tests or ECG or based on the opinion of the Investigator; 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 7 days 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 Use of ADHD medications throughout the study Use of any psychiatric medications throughout the study Use of investigational medication/treatment in the past 30 days prior to the screening visit per the discretion of the Investigator Use of any medication or food supplement not considered acceptable by the clinical Investigator or 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 consuming abnormally high amounts of caffeine during the study. Suicidality, defined as either active suicidal plan/intent or active suicidal thoughts, in the 6 months before the Screening Visit or no lifetime suicide attempt. Blind subjects 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 Pregnancy, lactation or inadequate contraceptive method -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: METADOXINE<br>Eligible subjects will be randomly assigned to receive MG01CI (1,400 mg) | Drug: Metadoxine (MG01CI)<br>* MG01CI 1400 mg, that will be taken daily by the patients for a duration of 6 weeks.<br>* Other names: Metadoxil;|
| Placebo Comparator: Placebo<br>Eligible subjects will be randomly assigned to receive Placebo (1,400 mg) | Drug: Metadoxine (MG01CI)<br>* MG01CI 1400 mg, that will be taken daily by the patients for a duration of 6 weeks.<br>* Other names: Metadoxil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conners' Adult ADHD Rating Scales (CAARS™) | The primary efficacy endpoint is the difference in change (decrease) in CAARS (Total ADHD Symptoms Score) between the study groups. The CAARS assess the presence and severity of ADHD symptoms and behaviors in adults. Respondents are asked to report their own experiences by rating items pertaining to their behavior/problems using a 4-point Likert-style format ranging from 0 ('Not at all', 'never') to 3 ('Very much', 'very frequently'). The scale measures ADHD symptoms using a 30-item questionnaire.Total score is the sum of all the items ,min=30 Max=90 | 6 weeks (from visit 1 baseline to visit 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test of Variables of Attention (TOVA) (Change in ADHD Score From Screening to Visit 6) | The 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. ADHD score is a comparison of the subject's response to the CPT test to those of an ADHD group, and is reported as a Z-score. An ADHD score of -1.80 and less fits the profile of the ADHD sample. A score of more than -1.80 (more positive) does not fit the ADHD profile. When comparing ADHD scores the higher the ADHD score the better the performance. | 6 weeks( visit 1 baseline to visit 6) | 
| Adult ADHD Quality of Life (AAQoL)- Measuring Change in Total Score of AAQoL From Visit 1 to Visit 6 | The AAQoL scale provides a validated disease-specific measure of the impact of ADHD on quality of life.It is scored as an overall score (29 items) and four subscale scores: life productivity (11 items), psychological health (6 items), life outlook (7 items) and relationships (5 items). Individual items are scored on a five-point Likert-like scale from 'Not at all/Never' (1) to 'Extremely/Very Often' (5). | 6 weeks (from visit 1 baseline to visit 6) | 
| Clinical Global Impression Scale (CGI-I)Score | The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-I scores range from 1 ('very much improved') through to 7 ('very much worse'). During the conduct of the study, CGI-I evaluations were not done correctly and thus data interpretation is limited. | 6 weeks from visit 1 baseline to visit 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD,Adults,MG01CI,METADOXINE