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

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

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

Study Overview

• Status: Completed
• Conditions: ADHD
• Intervention / Treatment: Drug: Metadoxine (MG01CI)

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

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • Cognitive Neurology unit Rambam Health Care Campus
  • Petah Tikva,, Israel
    • ADHD Unit, Geha Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult males and females, 18 to 50 years old, inclusive, at screening visit

2. 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
3. Clinical severity of at least a moderate level (Clinical Global Impression score of 4 or above)
4. Female subjects with childbearing potential must agree to use effective contraceptive and have negative urine pregnancy test at screening visit
5. Able to attend the clinic regularly and reliably
6. Able to swallow tablets/capsules
7. Able to understand, read, write and speak Hebrew fluently to complete study related materials
8. Able to understand and sign written informed consent to participate in the study

Exclusion Criteria:

1. Subjects who were non-responder to at least two ADHD treatments
2. 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
3. Any prescription or non-prescription ADHD medications during the 7 days prior to the screening visit
4. Known or suspected HIV-positive or with advanced diseases such as AIDS, Hepatitis C, Hepatitis B or tuberculosis
5. History of allergy or sensitivity to B complex vitamins
6. History or suspicion of PDD, NLD or other psychotic conditions
7. Use of Vitamin B throughout the study
8. Use of ADHD medications throughout the study
9. Use of any psychiatric medications throughout the study
10. Use of investigational medication/treatment in the past 30 days prior to the screening visit per the discretion of the Investigator
11. 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
12. 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.
13. 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.
14. Blind subjects
15. Any relation to the Sponsor, Investigator or study staff
16. 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.
17. 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

18. Pregnancy, lactation or inadequate contraceptive method

    -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alcobra Ltd.
• Investigators: Principal Investigator: Iris Manor, MD, Geha MC, Israel

Publications and helpful links

General Publications

• Manor I, Newcorn JH, Faraone SV, Adler LA. Efficacy of metadoxine extended release in patients with predominantly inattentive subtype attention-deficit/hyperactivity disorder. Postgrad Med. 2013 Jul;125(4):181-90. doi: 10.3810/pgm.2013.07.2689.
• Manor I, Ben-Hayun R, Aharon-Peretz J, Salomy D, Weizman A, Daniely Y, Megiddo D, Newcorn JH, Biederman J, Adler LA. A randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of extended-release metadoxine in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2012 Dec;73(12):1517-23. doi: 10.4088/JCP.12m07767.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: November 17, 2010
• First Submitted That Met QC Criteria: November 17, 2010
• First Posted (Estimate): November 18, 2010

Study Record Updates

• Last Update Posted (Estimate): April 20, 2012
• Last Update Submitted That Met QC Criteria: April 17, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: ADHD,Adults,MG01CI,METADOXINE
• Additional Relevant MeSH Terms: Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Alcohol Deterrents; Metadoxine
• Other Study ID Numbers: AL008