Clinical trial: A 6-week, Study of MG01CI Low Dose and High Dose Compared With Placebo in Adults and Adolescents With Fragile X Syndrome (NCT02126995)

Eligibility criteria:
Inclusion Criteria:

          1. Subject is a man or a non-pregnant, non-lactating woman aged 15 to 55 years,
             inclusive, at the Randomization Visit.

          2. Subject has Fragile X Syndrome with a molecular genetic confirmation of the full
             Fragile X Mental Retardation (FMR1) mutation (≥200 CGG repetitions).

          3. 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).

          4. 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.

               1. 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.

               2. 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.

               3. 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.

               4. Stimulant 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 end of the treatment period (Week 6/early termination), unless the subject is
                  washing out; see Exclusion Criterion 4.

          5. Behavioral treatments (excluding psychotherapy; see exclusion criteria) must be stable
             for 4 weeks prior to Screening and must remain stable during the period between
             Screening and the commencement of study medication.

          6. 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.

          7. 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.

          8. Subject and caregiver are able to attend the clinic regularly and reliably.

          9. Subject is able to swallow tablets and capsules.

         10. 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).

         11. 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.

         12. If subject is his/her own legal guardian, he/she can understand and sign informed
             consent to participate in the study.

         13. 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

        Exclusion Criteria:

          1. 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.

          2. Treatment within the 2 weeks prior to Screening with monoamine oxidase (MAO)
             inhibitors, tricyclic antidepressants, l-dopa, cisplatin, phenobarbital or phenytoin.

          3. Current treatment with an N-methyl-D-aspartate (NMDA) antagonist.

          4. 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.

          5. 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.

               1. A subject who started psychotherapy or CBT for the first time within 6 weeks
                  prior to Screening is excluded.

               2. 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.

          6. History of or current cardiovascular, renal, hepatic, respiratory, or gastrointestinal
             disease that may interfere with the absorption, distribution, metabolism, or excretion
             of the study medication, or that may interfere with the interpretation of the safety,
             tolerability, or efficacy of the study medication.

          7. History of or current cerebrovascular disease or clinically significant brain trauma.

          8. Current major depressive disorder (subject must be free of the most recent episode for
             3 months prior to randomization).

          9. History of a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
             (DSM-5)-defined substance use disorder in the 3 months prior to Screening.

         10. Clinically significant abnormalities, in the investigator's judgment, in safety
             laboratory tests, vital signs, or ECG, as measured at Screening.

         11. Significant hearing or visual impairment that may affect the subject's ability to
             complete the test procedures.

         12. Enrollment in another clinical trial within the 30 days preceding Screening.

         13. Any psychiatric condition (eg, schizophrenia or personality disorder as diagnosed by
             DSM-IV) or clinically significant or unstable medical or surgical condition that may
             preclude safe and complete study participation as determined by the investigator using
             medical history, physical examination, neurological examination, laboratory tests, and
             electrocardiograms. Common diseases such as mild hypertension, well-controlled type 2
             diabetes mellitus (hemoglobin A1C [Hgb A1C] <6.5%), 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 before randomization and subsequently throughout
             the study. If there are any concerns about the suitability of the subject's medical or
             surgical condition, the investigator should review the subject's history with the
             medical monitor. Subjects with autism spectrum disorder or anxiety disorder will be
             allowed.

         14. Subject has known or suspected human immune deficiency virus-positive status or has
             diseases such as acquired immunodeficiency disorder, hepatitis C, hepatitis B, or
             tuberculosis.

         15. Subject has a history of an allergy or sensitivity to B-complex vitamins.

         16. Subject has used mega-dose vitamin B6/pyridoxine during the 28 days before the
             Randomization Visit. Subjects will be allowed to have a 28-day washout of mega-dose
             vitamin B6/pyridoxine after the Screening visit. Routine multivitamin supplements will
             be allowed.

         17. Subject has used high-dose supplements of omega-3 fatty acids ≥ 500 mg (such as
             softgels, capsules, or fish oils; regular daily dietary consumption of fish is
             allowed) or folic acid supplements (other than routine multivitamin supplements) at
             any time during the 2 weeks before the Randomization Visit.

         18. Subject is related to anyone employed by the sponsor, investigator, or study staff.

         19. Subject has any condition that, in the principal investigator's opinion, would place
             the subject at risk or influence the conduct of the study or interpretation of
             results.

         20. Subject is pregnant, lactating, or using an inadequate contraceptive method. -
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 15 Years old.
Subject must be at most 55 Years

Patient description (medical language): A 15-year-old boy with mild intellectual disability is brought to the office by his parents for a routine physical examination.  The boy is going to a school for students with learning disabilities.  The patient was adopted, and his immunizations are up to date.  Review of the patient's medical records is notable for cytogenetic studies that showed a small gap near the tip of the long arm of the X chromosome, which is consistent with fragile X syndrome, an X-linked disorder. The defect is an unstable expansion of trinucleotide repeats (CGG) in the fragile X mental retardation 1 (FMR1) gene, located on the long arm of the X chromosome. He is not using any medications and vital signs are within normal levels. His blood chemistry analysis as bellow:
Blood Chemistry Value      Normal Range     Patient Value
Glucose                    90-120 mg/dl     95 mg/dl
BUN (Blood Urea Nitrogen)  7-24 mg/dl       10 mg/dl
Creatinine                 0.7-1.4 mg/dl    0.8 mg/dl
Calcium                    8.5-10.5 mg/dl   9 mg/dl
Sodium                     134-143 mEq/L    135 mEq/L
Potassium                  3.5-4.5 mEq/L    3.7 mEq/L
Chloride                   95-108 mEq/L     98 mEq/L
CO2                        20-30 mEq/L      25 mEq/L
Blood pH                   7.38-7.42        7. 39

Patient description (patient's own words): My husband and I brought our 15-year-old son to the clinic for his routine exam. My son is going to school for special needs students. We adopted him a few years ago. His vaccinations are up to date. He already passed some chromosome testing and they found that he has a fragile X syndrome. The doctor told us that it comes from repeats in the fragile X chromosome. My son is not using any medication and his blood pressure temperature and breathing were normal during the exam. He also did a blood test. The results came back and showed that his blood sugar urea creatinine calcium sodium potassium chloride CO2 and blood pH were all within the normal range.

Does the patient match the trial criteria? 1