An Initial Study of AZD7325 in Adults With Fragile X Syndrome

Inclusion Criteria:

- Diagnostic confirmation of full mutation FXS (at least partial gene methylation).

- 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.

- 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.