Crossover Study to Assess the Efficacy and Safety of UX007 in the Treatment of Movement Disorders Associated With Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

A Phase 3, Randomized, Double-blind, Placebo-controlled, Crossover Study to Assess the Efficacy and Safety of UX007 in the Treatment of Movement Disorders Associated With Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

The primary objective of the study was to evaluate the efficacy and safety of UX007 in the treatment of disabling paroxysmal movement disorders associated with Glut1 DS.

Inclusion Criteria:

1. Diagnosis of Glut1 DS confirmed by SLC2A1 mutation
2. Males and females, aged ≥6 years old at the time of informed consent
3. At least 8 disabling paroxysmal movement disorder events in the 12 weeks prior to the Screening, by subject or caregiver report or At least 6 disabling paroxysmal movement disorder events in any 6 consecutive week period, over the last 12 week period prior to the Screening, by subject or caregiver report
4. At least 4 disabling paroxysmal movement disorder events in 6 week Run-in Period, reported in the daily electronic Glut1 DS symptom diary
5. ≥80% compliance with daily electronic Glut1 DS symptom diary completion during the Run in Period
6. Not on ketogenic diet (KD), modified KD, or ketosis-inducing modified-fat diet for at least 3 months prior to Screening
7. Plasma level of beta-hydroxybutyrate (BHB) ≤ 1 mmol/L (non-fasting) at Screening
8. Provide written or verbal assent (if possible) and written informed consent by the patient(if an adult), or by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures
9. Must, in the opinion of the Investigator, be willing and able to complete key aspects of the study and be likely to complete the 22-week, placebo-controlled, treatment period
10. Patient (or caregiver) must, in the opinion of the Investigator, be able to comply with accurate completion of the study daily electronic Glut1 DS symptom diary
11. Females of child-bearing potential must have a negative urine pregnancy test at Screening and Baseline and be willing to have additional pregnancy tests during the study. Females considered not to be of child-bearing potential include those who have not experienced menarche, are post-menopausal (defined as having no menses for at least 12 months without an alternative medical cause) or are permanently sterile due to total hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
12. Participants of child-bearing potential or fertile males with partners of child-bearing potential who are sexually active must consent to use a highly effective method of contraception as determined by the site Investigator from the period following the signing of the informed consent through 30 days after last dose of study drug

Exclusion Criteria:

1. Any known hypersensitivity to triheptanoin or safflower oil that, in the judgment of the Investigator, places the subject at increased risk for adverse effects
2. Prior use of triheptanoin within 30 days prior to Screening
3. History of, or current suicidal ideation, behavior and/or attempts per Columbia Suicide Severity Rating Scale (C-SSRS) at Screening or Baseline
4. Pregnant and/or breastfeeding an infant at Screening or Baseline
5. Participants unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives (medium chain triglyceride [MCT] oil, barbiturates, pancreatic lipase inhibitors, KetoCal or other KD supplements, and/or KD])
6. Glut1 DS treatment regimen, including antiepileptic drugs (AEDs), should be stable for at least 30 days prior to Screening
7. Use of any investigational product (drug, medical food, or supplement, including MCT oil, including coconut oil) within 30 days prior to Screening
8. Has a concurrent disease or condition, or laboratory abnormality that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or introduces additional safety concerns
9. Feeding or nutrition that, in the opinion of the dietitian, potentially affects consistent administration of study drug