Pharmacokinetics Study of Oral 2-Deoxy-D-Glucose (2DG) in Subjects With a Confirmed Diagnosis of Epilepsy

NCT05605301 | Completed Phase 2 FDA Drug

• 1 other identifier: HSR210085
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Epilepsy; Seizure

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics

  AUC will be calculated from 2DG blood levels collected at time 0, 15, 30, 45, and 60 minutes and at 2, 4, 6, 12, and 24 hours after single dose of 2DG.

  Collected from time of drug administration to 24 hours post dose

• Incidence of Treatment-Emergent Adverse Events

  Spontaneously reported adverse events will be summarized by type and severity by the most recent version of MedRA terminology. Adverse events will be graded as mild, moderate, or severe and by whether the relationship to study drug is related, possibly related, or unrelated.

  From time of drug administration until 24 hours post-dose

Study Arms (1)

Sequential ascending dose cohort

EXPERIMENTAL

Cohort 1 will receive single 40 mg dose once. Cohort 2 will receive single 60 mg dose once. Cohort 3 will receive (2) 60 mg dose on one occasion.

Drug: Oral 2-Deoxy-D-Glucose (2DG)

Interventions

Oral 2-Deoxy-D-Glucose (2DG) DRUG

2DG will be formulated as an solid dosage form and administered orally.

Sequential ascending dose cohort

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Stable treatment regimen with no change in antiepileptic drugs or antiepileptic drug doses for 28 days prior to enrollment.
• Women of childbearing potential must be using a standard method of birth control and agree not to become pregnant during the trial. Men must agree to not father a child during the trial.
• BMI must be between 18 and 35.

You may not qualify if:

• Occurrence of non-epileptic psychogenic spells within 2 years prior to enrollment.
• Current or past history of diabetes or any abnormality of glucose metabolism.
• Use of glucocorticoids, hypoglycemic agents (e.g. metformin) or any drug that alters glucose levels.
• Use of any drug that is expected to alter glucose absorption, metabolism or serum measurements.
• Clinically significant psychiatric or medical disease.
• Previous therapeutic use of 2DG.
• Pregnant or nursing women.
• Use of an investigational medication within 2 months prior to enrollment.
• Supine systolic blood pressure \< 90 or \> 160 mm Hg or diastolic \> 90 mm Hg, or pulse \< 60 or \> 110 BPM.
• Clinically significant abnormal 12-lead ECG.
• Baseline prolongation of the QTc interval \> 450 msec.
• Clinically significant abnormal result by speckle tracking echocardiography (STE).
• Elevated ALT or AST more than 1.5 times upper reference limit.
• Baseline fasting glucose \< 60 or \> 110.
• History of status epilepticus within 6 months prior to enrollment.

Sponsors & Collaborators

• University of Virginia: lead
• Epilepsy Foundation: collaborator
• University of Wisconsin, Madison: collaborator

Study Sites (1)

University of Virginia School of Medicine

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Epilepsy

Interventions

Deoxyglucose

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Deoxy Sugars; Carbohydrates

Study Officials

• Nathan B Fountain, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Epileptology and Neurology

Model Details: 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

Study Record Dates

• First Submitted: October 22, 2022
• First Posted: November 4, 2022
• Study Start: September 2, 2022
• Primary Completion: February 5, 2024
• Study Completion: February 5, 2024
• Last Updated: February 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)