Treatment of Mitochondrial Dysfunction in Rett Syndrome With Triheptanoin
Treatment of Mitochondrial Dysfunction in Rett Syndrome With Triheptanoin
The aim of this study is to evaluate the safety and tolerability of triheptanoin in
 participants with Rett syndrome using laboratory values, electrocardiogram, rate of adverse
 events (AE), and physical exam.This study also seeks to evaluate the efficacy of UX007
 (triheptanoin) in improving overall seizure frequency and dystonia.
The aim of this study is to evaluate the safety and tolerability of triheptanoin in
 participants with Rett syndrome using laboratory values, electrocardiogram, rate of adverse
 events (AE), and physical exam. This study also seeks to evaluate the efficacy of UX007
 (triheptanoin) in improving overall seizure frequency, dystonia severity, and quality of
 life. Participants who are eligible will take triheptanoin daily. Participation in the
 primary arm of this study will last up to 8.5 months, with an optional 36 month extension.
Inclusion Criteria:

 -  Diagnosis of Classic Rett syndrome as defined by the clinical consensus criteria

 -  Presence of a MECP2 mutation

 -  Post-regression stage of development, defined as greater than 6 months since the last
 loss of hand use or verbal language

 -  Average of at least 4 observable seizures (generalized or partial-onset [Generalized
 Tonic-Clonic, Generalized Tonic, Generalized Clonic, Generalized Atonic, Partial/Focal
 with Secondary Generalization, Myoclonic, Myoclonic Atonic, Myoclonic Tonic, Complex
 Partial/Focal, and Simple Partial/Focal Motor) in one month prior to the study by
 caregiver report or presence of dystonia on average at least four times in one month
 prior to the study in at least one body region rated as at least "mild" by caregiver
 report

 -  Use of at least one anti-seizure medication at screening visit

 -  At screening visit, managed on four or fewer concomitant anti-seizure medications that
 must have been stable in dose at least one month prior to the beginning of screening
 and anticipated to remain stable in dose through the end of the 8.5 month trial period

 -  Legally authorized caregiver must be willing to give written informed consent after
 the nature of the study has been explained, and prior to any research-related
 procedures

 -  Caregiver and participant must, in the opinion of the investigator, be willing and
 able to complete all aspects of the study, comply with accurate completion of the
 seizure and dystonia diaries, and be likely to complete the four month treatment
 period

 Exclusion Criteria:

 -  Markedly abnormal metabolic screening laboratory testing (e.g., serum alanine
 aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2X the
 upper limit of normal)

 -  Any known hypersensitivity to triheptanoin that, in the judgment of the investigator,
 places the subject at increased risk for adverse effects

 -  Prior use of triheptanoin within 1 month prior to screening

 -  Participants or caregivers who are unwilling or unable to discontinue use of a
 prohibited medication or other substance that may confound study objectives

 -  Use of any other investigational product, including drugs or supplements within 1
 month prior to Screening, or at any time during the study

 -  Has a condition of such severity and acuity, in the opinion of the investigator, that
 it warrants immediate surgical intervention or other treatment

 -  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 (e.g., diabetes mellitus)

 -  Pregnant or nursing women