A 6-week, Study of MG01CI Low Dose and High Dose Compared With Placebo in Adults and Adolescents With Fragile X Syndrome

NCT02126995 | Completed Phase 2 DMC

• 1 other identifier: AL014
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 12

Brief Summary

This study is a multisite, randomized, double-blind, placebo-controlled, phase 2 study of MG01CI (low dose and high dose once daily) for 6 weeks compared with placebo in a 1:1 ratio of 60 adolescent and adult subjects with Fragile X Syndrome (FXS). Following Screening, subjects will be randomized to MG01CI or matching placebo at Baseline (Day 0) and the 6 week Double-blind Treatment Period will begin on Day 1. The first 4 weeks of the treatment period will be a dose-optimization period, All subjects will start with two daily tablets: low dose metadoxine or matching blinded placebo. At weekly visits/phone assessments, the investigator will evaluate the dose based upon the investigator's assessment of safety and tolerability. If the subject demonstrates safety or tolerability concerns with the low dose after 1 or 2 weeks of treatment, then the subject will be discontinued. If there are no concerns about safety and tolerability after 2 weeks of treatment, then the dose will be increased to high dose or placebo. If at the high dose there are concerns about safety and tolerability, then the dose will be either kept the same or reduced to low dose for the remainder of the treatment period. There will be a 2-week Follow-up Period after the last dose of study treatment or early termination.

Conditions

Fragile X Syndrome

Keywords

Fragile X Syndrome, Fra(X) Syndrome, FRAXA Syndrome

Outcome Measures

Primary Outcomes (1)

• Evaluation of efficacy of MG01CI by Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale (ADHD RS-IV)

  To evaluate the efficacy of MG01CI (Metadoxine Extended-release) once daily compared with placebo in the treatment of symptoms of FXS in adults and adolescents as measured by the inattentive subscale of the Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale (ADHD RS-IV) (as rated by the investigator in a clinical interview of the parent/legal authorized guardian/consistent caregiver).

  6 weeks

Secondary Outcomes (1)

• Evaluation of efficacy of MG01C as measured by total score on the ADHD RS-IV.

  6 weeks

Other Outcomes (4)

• Evaluation of safety by AE's count

  6 weeks

• Evaluation of safety by AE's vital sign measurements

  6 weeks

• Safety evaluation by lab tests (hematology, chemistry, and urinalysis)

  6 weeks

Study Arms (2)

Metadoxine Immediate/Slow-release

EXPERIMENTAL

Flexed and fixed-dose Metadoxine Immediate/Slow-release 700 mg and 1400 mg administered orally once daily

Drug: MG01CI extended-release tablet

Placebo

PLACEBO COMPARATOR

Placebo tablet identical in appearance to study investigational product. Administered orally once daily

Drug: MG01CI extended-release tablet

Interventions

MG01CI extended-release tablet DRUG

Metadoxine, MG01CI extended-release tablet taken for 6 weeks treatment. Starting with a dose of 700 mg for 2 weeks followed by a 2 weeks of 1400 mg and then 2 weeks of 700 mg or 1400 mg.

Also known as: Metadoxine (pyridoxol L-2-pyrrolidone-5-carboxylate)

Metadoxine Immediate/Slow-release; Placebo

Eligibility Criteria

• Age: 15 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subject is a man or a non-pregnant, non-lactating woman aged 15 to 55 years, inclusive, at the Randomization Visit.
• Subject has Fragile X Syndrome with a molecular genetic confirmation of the full Fragile X Mental Retardation (FMR1) mutation (≥200 CGG repetitions).
• Subject has a score of 12 or greater on the inattentive subscale of the ADHD RS IV (as rated by the investigator in a clinical interview of the parent/legal authorized guardian/consistent caregiver).
• Current treatment with no more than 3 prescribed psychotropic medications. Anti epileptic medications are permitted and are not counted as psychotropic medications if they are used for treatment of seizures. Anti-epileptics for other indications, such as the treatment of mood disorders, count towards the limit of permitted medications.
• Permitted concomitant psychotropic medications (except anti-epileptic medications and stimulants; see 4b and 4d) must be at a stable dose and dosing regimen for at least 4 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication.
• Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication.
• Subjects with a history of seizure disorder who are currently receiving treatment with anti-epileptics must have been seizure-free for 3 months preceding Screening, or must be seizure-free for 3 years if not currently receiving anti-epileptics.

You may not qualify if:

• Subject has a parent, legal authorized guardian or consistent caregiver who interacts with the subject for at least 10 hours per week and is able to provide weekly rating forms of the subject's behavior.
• Male and Female subjects of childbearing potential must agree to use an effective contraceptive throughout the study (eg, oral contraceptives or Norplant®; a reliable double barrier method of birth control \[diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam\]; intrauterine devices; vasectomy; or abstinence) and for at least a month after the study, and females must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit. Females of childbearing potential are defined as women who are between menarche and 2 years post-menopause and who are not surgically sterilized. Male and female subjects who are not sexually active, and who agree to be abstinent throughout the study, will not be required to use birth control.
• Subject and caregiver are able to attend the clinic regularly and reliably.
• Subject is able to swallow tablets and capsules.
• For subjects who are not their own legal guardian, subject's parent/legal authorized guardian is able to understand, read, write, and speak English fluently to complete the study-related materials (or Hebrew for Israeli subjects).
• For subjects who are not their own legal guardian, subject's parent/legal authorized guardian is able to understand and sign an informed consent form to participate in the study.
• If subject is his/her own legal guardian, he/she can understand and sign informed consent to participate in the study.
• If subject is not their own legal guardian, the subject provides assent for participation in the study, if the subject has the cognitive ability to provide assent
• Treatment within the 2 weeks prior to randomization (and throughout the clinical trial) with lithium, acamprosate, racemic baclofen, investigational metabotropic glutamate receptor subtype 5 (mGluR5) medications, d-cycloserine, oxytocin, carbetocin, modafinil, armodafinil, benzodiazepines (unless used for seizure control), memantine, amantadine, bupropion, or any medication in the statin class.
• Treatment within the 2 weeks prior to Screening with monoamine oxidase (MAO) inhibitors, tricyclic antidepressants, l-dopa, cisplatin, phenobarbital or phenytoin.
• Current treatment with an N-methyl-D-aspartate (NMDA) antagonist.
• While stimulants will not be excluded from the trial, the subject and the parent/legal authorized guardian may decide to stop stimulant medication prior to the study upon discussion with the investigator at the Screening visit. If stimulant medication is stopped at screening, a two-week washout is required. A subject that decides to washout from stimulants will be excluded from the trial if a stimulant is administered after the Screening visit or during the course of the trial.
• Subject is planning to commence psychotherapy or cognitive behavior therapy (CBT) during the period of the study or had begun psychotherapy or CBT within 6 weeks prior to Screening.
• A subject who started psychotherapy or CBT for the first time within 6 weeks prior to Screening is excluded.
• If a subject was previously receiving psychotherapy or CBT, and is resuming the therapy (such as return from summer vacation), then the subject is eligible for the study if the same therapy was resumed at least 2 weeks before screening.

Sponsors & Collaborators

• Alcobra Ltd.: lead

Study Sites (12)

Southwest Autism Research & Resource Center

Phoenix, Arizona, 85006, United States

Location

University of California Davis Pediatrics

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

RUSH University Medical Center

Chicago, Illinois, 60612, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Suburban Research Associates

Media, Pennsylvania, 19063, United States

Location

Baylor College of Medicine Research

Houston, Texas, 77030, United States

Location

Univ. of Washington/Seattle Children's Hospital

Seattle, Washington, 98121, United States

Location

Sheba Academic Medical Center

Ramat Gan, Israel, Israel

Location

MeSH Terms

Conditions

Fragile X Syndrome; Syndrome

Interventions

metadoxine

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Elizabeth Berry-Kravis, MD, PhD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2014
• First Posted: April 30, 2014
• Study Start: June 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: July 6, 2016

Record last verified: 2014-12

Locations

IL (1); US (11)