Safety and Tolerability Study of Metadoxine Extended Release (MDX) (Previously Known as MG01CI) in PI-ADHD Adolescent Subjects
Condition: ADHD, Predominantly Inattentive Type
MeSH terms: Attention Deficit Disorder with Hyperactivity
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to evaluate the safety and tolerability of a single
      administration of Metadoxine Extended Release (MDX) formulation for the treatment of
      adolescents diagnosed with ADHD that have predominantly inattentive symptoms. The study will
      also try to evaluate the efficacy of MDX and its level in the blood.
    

Detailed description: 
      This will be a randomized, double-blind, placebo-controlled multi-center, fixed dose, single
      dose study in adolescent subjects with PI-ADHD. Eligible subjects will be randomized in a 1:1
      ratio to receive single administration of either MDX (approximately 14-22 mg/kg) or matching
      placebo.

      Subjects taking a course of methylphenidate, amphetamine or atomoxetine at least two weeks
      prior to screening will require a 2-week wash-out (for methylphenidate, amphetamine) or a
      4-week wash-out (for atomoxetine) and be requested to attend an interim screening visit.

      The study will consist of three periods: a screening period of up to three weeks (and five in
      the case of atomoxetine washout), a 1 day treatment period, and a one-week safety follow-up
      period.

      Overview of Study Visits Screening Period - Visit 1 (Screening/Baseline) Following signing of
      informed consent/assent, subjects will be screened for study eligibility. Each subject will
      undergo a battery of evaluations with various rating scales including Adolescent ADHD
      Clinical Diagnostic Scale1 (ACDS v1.2), Kiddie - Schedule for Affective Disorders and
      Schizophrenia - Present and Lifetime Version (K-SADS-PL), Columbia-Suicide Severity rating
      scale (C-SSRS), State Trait Anxiety Inventory (STAI-A and STAI-T), Beck Depression Inventory
      (BDI), CGI-S (Clinical Global Impression - Severity), Time-Sensitive ADHD Symptom Scale
      (TASS), Wechsler Intelligence Scale for Children- fourth edition (WISC-IV) sub-tests2 and
      Test of Variables of Attention (TOVA)3. Eligible subjects who did not require a wash-out,
      will be eligible for the study. In addition, the following standard assessments will be
      performed: assessment of inclusion/exclusion, collection of demographic data, medical
      history, prior medications, neurological exam, neuropathy questionnaire, physical exam,
      height and weight, vital signs, ECG, laboratory evaluations including hematology (complete
      blood count, CBC), chemistry, plasma concentration of metadoxine, urinalysis, and serum
      pregnancy test for women of child bearing potential. The screening visit may be conducted
      over multiple days. Screening visit data will be considered baseline data for statistical
      analysis purposes for subject requiring no washout.

      Visit 1a (Interim screening visit) This visit is applicable to subjects taking medications or
      supplements requiring washout such as methylphenidate, amphetamine or atomoxetine at any time
      during the 2 weeks preceding Visit 1 (screening); these subjects will undergo a 2-week
      washout (for cases such as methylphenidate or amphetamine treatment) or a 4-week washout (for
      cases such as atomoxetine treatment) period after which they will attend an interim screening
      visit. Baseline TOVA, WISC-IV sub-tests1, and TASS will be performed at Visit 1a. In
      addition, the C-SSRS, adverse events, and concomitant medications will be recorded at this
      visit.

      Treatment Period - Visit 2 (Day 1, visit window + 3 days) At study visit 2 (Day 1), each
      eligible subject will be randomized in a 1:1 allocation to receive either MG01CI or matching
      placebo; dose will be determined by weight at screening visit 1. Investigational product will
      be administered at the clinic. The WISC-IV sub-tests of Digit Span, Coding, Letter Number
      Sequencing, and Symbol Search will be administered. Subjects will undergo evaluations with
      the TOVA test 3 to 5 hours post-dose to assess their response to treatment. In addition,
      subjects will complete the TASS prior to administration of study drug, and 3-5 hours
      post-dose. At this visit, the subjects will also undergo safety assessments including urine
      pregnancy test (pre-dose), vital signs , neurological exam, neuropathy questionnaire, the
      C-SSRS and recording of adverse events (AEs) and concomitant medications. Subjects will have
      blood drawn for plasma concentrations of metadoxine at 1-2 hours post-dose and 3-4 hours
      post-dose.

      Follow-Up Period - Visit 3 (Day 8, visit window ± 3 days) One week after the end of
      treatment, subjects will complete the TASS and will undergo safety assessments including
      physical exam, neurological exam, neuropathy questionnaire, vital signs, ECG, laboratory
      evaluations (hematology, chemistry, and urinalysis including urine pregnancy test for women
      of child bearing potential), the C-SSRS, and documentation of concomitant medications and
      AEs, if any.
    

Intervention name(s): Metadoxine extended release; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): MG01CI; Inactive drug
Other intervention name(s): MDX; Sugar pill
Intervention MeSH terms: Metadoxine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: ADHD; Inattention; MDX