ADHD, Predominantly Inattentive Type Clinical Trial
Official title:
Randomized, Double-blind, Placebo-controlled, Multi-center, Fixed Dose Study Designed to Evaluate the Safety and Tolerability of a Single Administration of MG01CI (Metadoxine Extended Release, MDX) in Adolescents With Predominantly Inattentive Attention Deficit Hyperactivity Disorder
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.
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.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment