A Study to Evaluate Ketamine for the Treatment of Rett Syndrome

A Randomized, Double-blind, Placebo-controlled, Cross-over Study to Assess the Safety, Tolerability and Efficacy of Oral Ketamine for Patients With Rett Syndrome

This 2 cohort, sequential, ascending dose study will assess the safety, tolerability and efficacy of oral ketamine dosed in a single 5-day BID regimen in addition to placebo, in a 4-week cross-over design in patients with Rett Syndrome. Approximately 12 patients per cohort are anticipated to participate for approximately 8-10 weeks at approximately 7 US study centers.

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 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 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.