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

Phase 2

Completed

Conditions: ADHD

Interventions: Drug: Metadoxine (MG01CI)

Registration Number: NCT01243242

Lead Sponsor: Alcobra Ltd.

Brief Summary: 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: 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 120

Inclusion Criteria

Adult males and females, 18 to 50 years old, inclusive, at screening visit
Diagnosed with ADHD based on
1. DSM-IV criteria for ADHD as assessed by the Adult ADHD Clinician Diagnostic Scale (ACDS V1.2)
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
METADOXINE	Metadoxine (MG01CI)	Eligible subjects will be randomly assigned to receive MG01CI (1,400 mg)
Placebo	Metadoxine (MG01CI)	Eligible subjects will be randomly assigned to receive Placebo (1,400 mg)

Primary Outcome Measures

Name	Time	Method
Conners' Adult ADHD Rating Scales (CAARS™)	6 weeks (from visit 1 baseline to visit 6)	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

Secondary Outcome Measures

Name	Time	Method
Test of Variables of Attention (TOVA) (Change in ADHD Score From Screening to Visit 6)	6 weeks( visit 1 baseline 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.
Adult ADHD Quality of Life (AAQoL)- Measuring Change in Total Score of AAQoL From Visit 1 to Visit 6	6 weeks (from visit 1 baseline 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).
Clinical Global Impression Scale (CGI-I)Score	6 weeks from visit 1 baseline to visit 6	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.