Ataluren for Nonsense Mutation in CDKL5 and Dravet Syndrome

Investigators will try to characterize the safety profile of ataluren in patients with CDKL5
or Dravet syndrome resulting from a nonsense mutation and evaluate changes in convulsive
and/or drop seizure frequency from Baseline following ataluren treatment in patients with
CDKL5 or Dravet syndrome resulting from a nonsense mutation. Investigators will measure
changes in minor seizure types (absence, myoclonic, complex partial/focal dyscognitive)
following ataluren treatment in patients with CDKL5 or Dravet syndrome resulting from a
nonsense mutation and changes from Baseline in cognitive, motor, and behavioral function as
well as QOL following ataluren treatment in patients with CDKL5 or Dravet syndrome resulting
from a nonsense mutation.

Inclusion Criteria:

1. Age ≥ 2 years old and ≤ 12 years old, male or female, at Week 0 (at time informed
consent/assent is signed)

2. Documentation of a diagnosis of Dravet syndrome or CDKL5 deficiency resulting from a
nonsense mutation in 1 allele, as evidenced by medical records, genetic testing, and
the following clinical feature:

a. Failure to control seizures despite appropriate trial of 2 or more AEDs at
therapeutic doses

3. Between 1 to 3 baseline AEDs at stable doses for a minimum for 4 weeks prior to the
Baseline visit

a. Vagus nerve stimulator (VNS), ketogenic diet, and modified Atkins diet do not count
towards this limit but must be unchanged for 3 months prior to enrollment (Baseline).

4. VNS must be on stable settings for a minimum of 3 months prior to the Baseline visit

5. If on ketogenic or modified Atkins diet, must be on stable ratio for a minimum of 3
months prior to the Baseline visit

6. Written consent obtained from the patient or patient's legal representative must be
obtained prior to performing any study procedures

7. Minimum of 6 convulsive or drop seizures with duration > 3 seconds over the 4 weeks of
diary screening prior to randomization and ≥ 6 convulsive or drop seizures with
duration > 3 seconds during the 4 weeks from Screening to Baseline.

Exclusion Criteria:

1. Patient is < 2 years old or ≥ 12 years old

2. Epilepsies associated with genetic disorders other than Dravet syndrome or CDKL5
deficiency

3. Patient has Dravet or CDKL5 genetic mutations that are NOT nonsense mutations

4. Felbatol has been initiated within the past 12 months prior to the Screening Visit

5. Patients who are currently or have participated in clinical trials in the 30 days
prior to enrollment (Baseline Visit)

6. Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition),
medical history, physical findings, or laboratory abnormality that, in the
investigator's opinion, could adversely affect the safety of the patient, makes it
unlikely that the course of study drug administration or follow-up would be completed,
or could impair the assessment of study results.

7. Ongoing intravenous administration of aminoglycosides or vancomycin.