OER Glibenclamide for Neuropathic Pain in Multiple Sclerosis

This is a 2-stage pilot study of the pharmacodynamics and clinical effects of OER glibenclamide in MS patients with neuropathic pain. This pilot study will include 10 subjects. In Stage 1 of the study, which will last 5 days, unblinded subjects will take test-drug twice daily each day and participate in PK determinations. Successful completion of this Stage will establish the ability of a subject to safely tolerate the test-drug. In Stage 2 of the Study, which will last 3 months, blinded subjects who have demonstrated the ability to safely tolerate the test-drug will be asked to evaluate its clinical efficacy specifically with regard to neuropathic pain. By using a 3-block/on-off design with blinding, each subject will serve as their own control during the Stage-2 efficacy part of the study.

Inclusion criteria

• Age 18-65
• Diagnosis of multiple sclerosis per the 2017 Revised McDonald Criteria
• Score of ≥ 19 on the painDETECT questionnaire

Exclusion criteria

• Severe renal disorder from the patient's history (e.g., dialysis) or eGFR of < 30 ml/min.1.73m2
• Severe liver disease, or ALT > 3 times upper limit of normal or bilirubin >2 times normal
• Acute ST elevation myocardial infarction, and/or acute decompensated heart failure, and/or QTc > 520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole), and/or admission for an acute coronary syndrome, myocardial infarction, or coronary intervention within the past 3 months
• T2DM treated with insulin or oral medication
• Blood glucose < 55 mg/dL at enrollment or immediately prior to administration of study drug or a clinically significant history of hypoglycemia.
• Known sulfonylurea treatment within 7 days. Sulfonylureas include glyburide/glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride (Amaryl); repaglinide (Prandin); nateglinide (Starlix); glipizide (Glucotrol, GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase); glibornuride (Glutril)
• Known allergy to sulfa or specific allergy to sulfonylurea drugs
• Known G6PD enzyme deficiency
• Pregnancy. Women must be either postmenopausal, permanently sterilized or, if ≤50 years old must have a negative test for pregnancy obtained before enrollment
• Breast-feeding women who do not agree to stop breastfeeding during Study Drug infusion and for 7 days following the end of Study Drug infusion