Clinical trial NCT01243242: Clinical Efficacy & Safety, of Metadoxine (MG01CI) Extended Release in Attention-Deficit Hyperactivity Disorder (ADHD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: ADHD
Keywords: ADHD,Adults,MG01CI,METADOXINE
Lead sponsor: Alcobra Ltd.
Sponsor class: INDUSTRY
First posted: 2010-11-18
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

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Primary outcomes:
measure: Conners' Adult ADHD Rating Scales (CAARS™)
timeFrame: 6 weeks (from visit 1 baseline to visit 6)
Secondary outcomes:
measure: Test of Variables of Attention (TOVA) (Change in ADHD Score From Screening to Visit 6)
timeFrame: 6 weeks( visit 1 baseline to visit 6)
measure: Adult ADHD Quality of Life (AAQoL)- Measuring Change in Total Score of AAQoL From Visit 1 to Visit 6
timeFrame: 6 weeks (from visit 1 baseline to visit 6)
measure: Clinical Global Impression Scale (CGI-I)Score
timeFrame: 6 weeks from visit 1 baseline to visit 6
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Cognitive Neurology unit Rambam Health Care Campus
city: Petah Tikva,
country: Israel
facility: ADHD Unit, Geha Mental Health Center
Study officials:
affiliation: Geha MC, Israel
name: Iris Manor, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.