Clinical trial: An Initial Study of AZD7325 in Adults With Fragile X Syndrome (NCT03140813)

Eligibility criteria:
Inclusion Criteria:

          -  Diagnostic confirmation of full mutation FXS

          -  50 ≥ Age ≥18 years. Males and Females included in study.

          -  General good health as determined by physical exam, medical history and laboratory
             work up.

          -  FXS genetic reports at screening

          -  IQ less than or equal to 80. Note: IQ cutoff is used as a means to exclude cases of
             females with FXS who have the full mutation, but may have neurotypical development
             (ie: do not have the full FXS phenotype despite positive FXS genetic testing) due to
             variability in X chromosome inactivation patterns.

          -  Male study participants who are sexually active with a female partner of childbearing
             potential must be surgically sterilized, practicing abstinence, or agree to use highly
             effective methods of birth control (defined in the list below), and not rely on
             barrier methods and spermicide alone, from the time of screening until 1 week after
             final dose of study drug. Male study participants must also not donate sperm from the
             time of screening until 1 week after final dose of study drug. Given that AZD7325 is
             not mutagenic, there is no mandatory requirement for condom use, either for avoidance
             of procreation or in the case of treated males with a pregnant partner.

          -  Women of childbearing potential may be included in the study provided they are
             established on, and continue to use, highly effective contraceptive methods from the
             time of screening until 1 week after the final dose of study drug. Highly effective
             methods of contraception associated with inhibition of ovulation (either oral,
             intravaginal or transdermal), progestin-only hormonal contraception associated with
             inhibition of ovulation (either oral [specifically Micronor, Nor-QD or their generic
             equivalents], injectable or implantable).

          -  Aberrant Behavior Checklist total score of 20 or higher at screening

        Exclusion Criteria:

          -  Concomitant use of modulators of GABA A neurotransmission. (examples)

          -  Use of more than three psychotropic drugs that do not directly impact GABA
             transmission, and/or unstable dosing of any psychotropic medication in the 4 weeks
             prior to baseline visit.

          -  Subjects are prohibited from use of strong and moderate modulators of CYP3A and
             CYP2C19 during the screening (at least 2 weeks before initiation of the study) and
             treatment periods of the study. Such prohibited drugs are outlined in
             http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/u
             cm292362.pdf

          -  CNS-suppressing agents such as central analgesics, muscle relaxants, benzodiazepines,
             other sedatives, and should also limit alcohol intake to ≤1 alcoholic beverage per
             day.

          -  Unstable seizure disorder as defined by any seizure in the 6 months prior to baseline
             visit and/or a change in any anti-convulsant drug dosing in the 60 days prior to study
             entry.

          -  All patients with abnormal baseline safety lab assessments including, but not limited
             to ALT or AST greater than 1.5 the upper limit of normal, total bilirubin or
             creatinine greater than 1 time the upper limit of normal or other clinically relevant
             lab abnormality or abnormality in ECG, HR or BP at screening as judged by the
             investigator.

          -  Clinical relevant history or presence of any medical disorder judged by the
             investigator at potentially interfering with this trial.

          -  History of or current abuse of drugs or alcohol including prescription medication.

          -  For female subjects of child bearing potential (women 50 & under is "amenorrhoeic for
             12 months or more (following cessation of exogenous hormonal treatments - if these
             have been previously taken) and with luteinizing hormone (LH) and follicle stimulating
             hormone (FSH) levels in the post-menopausal range) a positive pregnancy test.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 50 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? Contradiction