An Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome

Triheptanoin is proposed for the treatment of seizures in glucose transporter type-1
deficiency syndrome (Glut1 DS). Glut1 DS is a rare disease with an estimated US prevalence of
~3,300.

The proposed study is an open-label study to assess the safety and long-term efficacy of
triheptanoin in patients with Glut1 DS over a 5-year treatment period. Eligible patients may
be those who are able to tolerate triheptanoin if they have been treated or are currently
being treated with triheptanoin and do not qualify for any other clinical trial. Subjects
previously treated with triheptanoin will continue to dose at approximately 35% of total
daily calories (~1-4g/kg/day, depending on age). Subjects who are naïve to triheptanoin will
begin a 2-week fixed titration schedule up until they have reached 35% of total daily
calories.

The primary objective of the study is to evaluate the safety of triheptanoin via adverse
event rates and laboratory values. The secondary objective is to evaluate the long-term
efficacy of triheptanoin as measured by the change in seizure frequency from historical
baseline.

Inclusion Criteria:

Individuals eligible to participate in this study must meet all of the following criteria:

1. Patients with GLUT1 DS by physician diagnosis

2. Males and females, aged 1 to 50 years

3. Allowed to be on concomitant AEDs

4. Patients are able to tolerate triheptanoin if they have been (or are currently being)
treated with this medication

5. Must, in the opinion of the investigator, be willing and able to comply with study
procedures and schedule

6. Provide written assent (if appropriate) and written informed consent by a Legally
Authorized Representative (LAR) after the nature of the study has been explained, and
prior to any research-related procedures

7. Sexually active subjects must be willing to use an acceptable method of contraception
while participating in the study

8. Females of childbearing potential must have a negative pregnancy test at Screening and
be willing to have additional pregnancy tests during the study

Exclusion Criteria:

Individuals who meet any of the following exclusion criteria will not be eligible to
participate in the study:

1. Patients and their Legally Authorized Representatives (as appropriate) not willing or
able to give written or verbal assent or written informed consent.

2. Concomitant administration of a ketogenic diet for the treatment of GLUT1 deficiency

3. Concomitant administration of valproic acid

4. In the Investigator's opinion, the patient may not be compliant

5. Pregnant or breastfeeding an infant at screening

6. Has a concurrent disease or condition, or laboratory abnormality that, in the view of
the Investigator, places the subject at high risk for adverse events, or introduces
additional safety concerns

7. History of or current suicidal ideation, behavior and attempts

8. Patient qualifies for any other clinical trial designed to progressively evaluate the
safety and efficacy of triheptanoin as approved by the FDA under a separate IND which
is open at Cook Children's