Pharmacokinetics Study of Oral 2-Deoxy-D-Glucose (2DG) in Subjects With a Confirmed Diagnosis of Epilepsy
Status:
Recruiting
Trial end date:
2023-10-01
Target enrollment:
Participant gender:
Summary
This project studies how 2-deoxy-glucose (2DG) pills are absorbed and distributed in people
with epilepsy. 2DG is similar to glucose, the main energy source for the brain, but it cannot
be used as energy. During seizures, neurons are at a very high metabolic state with huge
glucose metabolism as glycolysis is accelerated to supply the high metabolic needs of a
seizure. 2DG is taken up by cells but cannot be metabolized by the first enzyme in the
glycolytic pathway, thus is stops, or "clogs up", glycolysis. Since brain metabolism is
almost entirely dependent on glucose as an energy source, glycolysis is arrested and may stop
seizures. It is hoped that 2DG will stop seizures by interfering with the brain's energy use.
This is an open-label phase 2 study of the pharmacokinetics (PK), safety, and tolerability of
2DG administered orally to adult epilepsy patients. A 3-level 2DG dose escalation is planned
in sequential cohorts of 3 subjects in each cohort with review of each cohort before
proceeding to the next cohort. On the day of oral 2DG exposure, subjects will receive a
single dose of 40 mg in the first cohort, a single dose of 60 mg in the second cohort, and
two 60 mg doses (60 mg bid) in the third cohort.
After 3 subjects have completed dosing at Dose Level 1 (40 mg/day), the safety and PK results
will be reviewed. The Study Committee will determine if the next cohort should be enrolled at
Dose Level 2 (60 mg/day). The same procedure will be repeated to determine if the next cohort
should be enrolled at Dose Level 3 (60 mg bid = 120 mg/day). If the Study Committee
determines that the most recent dose is not tolerated or that there are significant adverse
events, the subsequent Dose Level will not be enrolled.
A standard time-concentration curve will be constructed from the 2DG levels obtained from the
PK blood draws. Parameters will be calculated for: time to maximum concentration (tmax),
maximum concentration (Cmax), elimination rate, half-life (t1/2), AUC, and derived
parameters. Statistical analysis will not be performed because of the small n, but this will
nevertheless establish the PK profile of 2DG in people with epilepsy. The most important
parameter will be the AUC which determines drug exposure.
Phase:
Phase 2
Details
Lead Sponsor:
University of Virginia
Collaborators:
Epilepsy Foundation University of Wisconsin, Madison