A Study to Evaluate Ketamine for the Treatment of Rett Syndrome

This study is designed to assess oral ketamine for the treatment of Rett Syndrome and
consists of up to 4 ascending dose cohorts, each assessing 1 dose level of ketamine vs
placebo. Patients will receive in either order, a 5-day BID regimen of both placebo and the
cohort-specified dose level of oral ketamine. Patients may only participate in 1 cohort.
Safety and tolerability will be assessed via patient disposition, vital signs, physical
examination, adverse events and concomitant medication use. Efficacy will be assessed via
physician and caregiver questionnaires and assessments, and continuous, wearable, at-home
biosensor data collection. An independent safety committee will review safety data from each
cohort to determine if the subsequent ascending dose cohort is warranted. A total of 12
patients per cohort and up to 48 patients in total is anticipated at approximately 7 sites.
The screening period will last between 2 and 4 weeks, the cross-over treatment period will
last 4 weeks, and the safety follow-up period will last 2 weeks. Total patient participation
is approximately 8-10 weeks.

Inclusion Criteria:

- Female Rett Syndrome patients diagnosed with typical Rett Syndrome with a confirmed
MECP2 mutation

- between the ages of 6 and 12, inclusive, who have not achieved menarche

- ability to take oral medications

- are generally healthy.

Exclusion Criteria:

- Patients not on stable medication regimens/other types of behavioral, educational, or
dietary interventions for at least 4 weeks,

- are taking medications that may interact with ketamine,

- have a condition where increased blood pressure, spinal fluid pressure, or ocular
pressure may put the patient at increased risk.