A randomized, double-blind, placebo-controlled, crossover study to assess the safety, tolerability, and pharmacokinetics of single doses of AUT00201 at 100 mg or matching placebo in patients with myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK).

6 to 10 patients aged 18 years and older, diagnosed with MEAK will be enrolled in the study. Patients will be administered a single dose of AUT00201 and matching placebo in a crossover design. The study is comprised of an outpatient screening and procedure orientation followed by approximately 5 days of an inpatient stay at a clinical research unit. After screening/orientation (Visit 1), and baseline assessments (Visit 2), patients will be administered a single dose of 100 mg of AUT00201 or matching placebo the morning of Visit 3. PK assessments will be done at Visits 3, 4, 5, and 6 from predose and up to 27 hours postdose. Visit 4 will be a washout day for patients. At Visit 5 patients will be administered the crossover treatment. At Visit 6 patients will be discharged from the unit. Safety and tolerability assessments will be conducted throughout. PD parameters will also be assessed. Patients will be followed up by telephone 14 days after discharge.

Inclusion Criteria:

• Male or female patients aged 18 years or older at time of consenting.
• Diagnosed with MEAK, based on documented genetic evidence of the presence of the KCNC1 (c.959G>A; p.Arg320His) variant.
• If take anticonvulsants, must be on a stable anticonvulsant regiment for at least 30 days prior to Visit 1 and anticipated to remain stable throughout the study or if not on an anticonvulsant regimen, must be stable in regards to seizures for at least 30 days prior to Visit 1 and anticipated to remain stable throughout the study.
• Must be able to participate and willing to give written informed consent. If patient is unable to provide written informed consent, a legally authorized representative can sign on their behalf.
• Must be willing to perform study assessments and comply with the study protocol.
• If the patient is dependent on a caregiver and/or will need assistance either travelling to the site, whilst attending clinic visits and/or helping to document study assessment responses provided by the patient (eg, questionnaires administered on a tablet device), they must have an identified caregiver, considered reliable by the Investigator, to provide support to the patient for the duration of the study. The caregiver must be willing and able to provide support to the patient and, if required, stay for the duration of the study.
• Medically stable based on Investigator's judgement for at least 90 days prior to Visit 1.
• Women of childbearing potential must have a negative urine pregnancy test on Visit 2.
• If a vagal nerve stimulator is used, it must be implanted at least 150 days before Day. -1, and parameters must be stable for at least 30 days before Visit 1 and expected to remain stable throughout the study.
• If a ketogenic diet is followed, it must be stable for at least 30 days before Visit 1 and expected to remain stable throughout the study.
• Willing to comply with contraceptive requirements.
• Able to speak, read and understand English at a fluent level

Exclusion Criteria:

• Known pathogenic mutation in another gene that causes epilepsy or a different mutation in the KCNC1 gene than the c.959G>A variant.
• Clinically significant metabolic, hepatic, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder.
• Clinically significant abnormal vital signs or laboratory test results.
• Hypersensitivity to AUT00201 or any of the excipients.
• Any medical condition or other factors, as judged by the Investigator, which may interfere with the patient's participation in this study and/or compromise the patient's ability to safely complete the study.
• Known to abuse drugs or those who test positive on urine screen for drugs of abuse will be excluded based on Investigator's judgement.
• Positive hepatitis B surface antigen or hepatitis C antibody.
• Clinically significant abnormality on the 12-lead electrocardiogram.
• Having received an investigational product 90 days prior to Visit 1.
• Currently using felbamate <1 year prior to Visit 1, or any evidence of ongoing hepatic or bone marrow dysfunction associated with current/prior felbamate treatment. Patients who are currently using felbamate for >1 year prior to Visit 1 and have no evidence of ongoing hepatic or bone marrow dysfunction associated with felbamate treatment are allowed.
• Currently using vigabatrin and having received vigabatrin for <2 years prior to Visit 1.
• Suicidal ideation with some intent to act within 6 months prior to Visit 1 based upon response in the Columbia-Suicide Severity Rating Scale (positive response to questions 4 or 5 of the suicidal ideation section) and as judged by the Investigator as having a significant impact on trial participation or patient safety. History of suicidal behavior within 1 year prior to Visit 1.

Adverse events, based on clinical signs and symptoms and laboratory measurements, were collected from the time the ICF was signed until follow up phone call (end of study) Visit 7 (Study Day 18±2 days).