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)
Condition: Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
MeSH terms: Movement Disorders; Carbohydrate Metabolism, Inborn Errors; Syndrome
Intervention: UX007; Placebo
Intervention description: liquid for oral (PO) administration; liquid safflower oil for PO administration
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 44.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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