Clinical trial: A 2-Period Crossover Study of BPN14770 in Adults Males With Fragile X Syndrome (NCT03569631)

Eligibility criteria:
Inclusion Criteria:

          1. Subject is male aged 18 to 45 years, inclusive.

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

          3. 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.

          4. Permitted concomitant psychotropic medications must be at a stable dose and dosing
             regimen for at least 2 weeks prior to Screening and must remain stable during the
             period between Screening and the commencement of study medication.

          5. 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.

          6. 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.

          7. Behavioral and therapy treatments/interventions must be stable for 4 weeks prior to
             Screening and must remain stable during the period between Screening and the
             commencement of study medication, and throughout the study. Minor changes in hours or
             times of therapy that are not considered clinically significant will not be
             exclusionary. Changes in therapies provided through a school program, due to school
             vacations, are allowed.

          8. Subject must be willing to practice barrier methods of contraception while on study,
             if sexually active. Abstinence is also considered a reasonable form of birth control
             in this study population.

          9. Subject has a parent, legal authorized guardian or consistent caregiver.

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

         11. Subject is able to swallow tablets and capsules.

         12. 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.

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

         14. 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. History of, or current cardiovascular, renal, hepatic, respiratory, gastrointestinal,
             psychiatric, neurologic, cerebrovascular, or other systemic disease that would place
             the subject at risk or potentially interfere with the interpretation of the safety,
             tolerability, or efficacy of the study medication. 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 4 weeks before
             randomization.

          2. Renal impairment, defined as serum creatinine > 1.25 x ULN at screening

          3. Hepatic impairment, defined as ALT or AST elevation > 2 x ULN at screening. Note:

             LFTs may be repeated after 1 week to evaluate return to acceptable limits; if LFTs
             remain elevated, subject is ineligible to participate.

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

          5. History of substance abuse within the past year, according to investigator assessment.

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

          7. Concurrent major psychiatric condition (e.g., Major Depressive Disorder, Schizophrenia
             or Bipolar Disorder) as diagnosed by the investigator. Subjects with additional
             diagnosis of Autism Spectrum Disorder or Anxiety Disorder will be allowed.

          8. Subject has active diseases that would interfere with participation, such as acquired
             immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis.

          9. Subject is planning to commence psychotherapy or cognitive behavior therapy (CBT)
             during the period of the study or had begun psychotherapy or CBT within 4 weeks prior
             to Screening.

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

         11. Subject has BMI less than 18 or greater than 36.

         12. Subject has participated in another clinical trial within the 30 days preceding
             Screening.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 45 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? 0