Pharmacokinetics Study of Oral 2-Deoxy-D-Glucose (2DG) in Subjects With a Confirmed Diagnosis of Epilepsy
Condition: Epilepsy; Seizure
MeSH terms: Epilepsy; Seizures
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      The study will be conducted as a 1-day Monitored Dosing and Pharmacokinetics Period in an
      inpatient setting. Subjects will report to the hospital in a fasted state (since midnight) on
      the morning of the pharmacokinetics study. Subjects will continue to fast until one hour
      after the 2DG dose has been given. 2DG will be given as either a single oral dose (40 mg for
      Dose Level 1; 60 mg for dose level 2) or 60 mg bid (Dose Level 3). Blood for pharmacokinetic
      analysis will be drawn at time 0 (prior to drug administration), and then at 15, 30, 45, and
      60 minutes and at 2, 4, 6, 12, and 24 hours after single dose 2DG administration. Blood for
      pharmacokinetic analysis will be drawn at time 0 (prior to drug administration) and then at
      15, 30, 45, and 60 minutes and at 2, 4, 6, 12, and 24 hours after the last dose for Dose
      Level 3. Patients will be closely monitored for safety during and following dosing with 2DG.
    

Intervention name(s): Oral 2-Deoxy-D-Glucose (2DG)
Intervention type(s): Drug
Intervention description(s): 2DG will be formulated as an solid dosage form and administered orally.
Intervention MeSH terms: Deoxyglucose
Intervention model: Sequential Assignment
Intervention model description: Subjects will be given 2DG orally during a single day of dosing at one of three sequential dose levels (a single dose of 40 mg for Dose Level 1, a single dose of 60 mg for Dose Level 2, or 60 mg bid for Dose Level 3). The total dose will not exceed 120 mg/day, or 60 mg maximum.
as a single dose
Masking: None (Open Label)
Primary purpose: Treatment