OER Glibenclamide for Neuropathic Pain in Multiple Sclerosis

University of Maryland Baltimore (UMB)

Status and phase: Begins enrollment in 6 months; Phase 1

Conditions: Multiple Sclerosis; Neuropathic Pain

Treatments: Drug: Placebo; Drug: glibenclamide

Study type: Interventional

Funder types: Other

Identifiers

NCT07221799

HP-00115908

Details and patient eligibility

About

This is an early phase safety evaluation of the use of oral extended release (OER) glibenclamide, which is otherwise known as glyburide, for use as a treatment for neurologic pain in people with multiple sclerosis. Patients will receive medication to assess safety and tolerability.

Full description

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.

Enrollment: 10 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Severe renal disorder from the patient's history (e.g., dialysis) or eGFR of < 30 ml/min.1.73m2
2. Severe liver disease, or ALT > 3 times upper limit of normal or bilirubin >2 times normal
3. 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
4. T2DM treated with insulin or oral medication
5. Blood glucose < 55 mg/dL at enrollment or immediately prior to administration of study drug or a clinically significant history of hypoglycemia.
6. 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)
7. Known allergy to sulfa or specific allergy to sulfonylurea drugs
8. Known G6PD enzyme deficiency
9. Pregnancy. Women must be either postmenopausal, permanently sterilized or, if ≤50 years old must have a negative test for pregnancy obtained before enrollment
10. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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10 participants in 2 patient groups, including a placebo group

oral extended release glibenclamide

Experimental group

Description:

1. Stage 1, Pharmacokinetics/Pharmacodynamics: This will be a 5 day, unblinded evaluation while participants receive OER-glibenclamide 2. Stage 2, Safety/Efficacy: This part of the study occurs during weeks 2-13, in 3 successive blocks of 4 weeks each. During this stage, group assignments are randomized, and subjects are blinded as to test-drug vs. placebo. Depending on group assignment, exposure to test-drug may occur early (week-2) or later (week-6). In both groups, exposure to placebo occurs for 4 weeks and exposure to drug occurs for 8 successive weeks.

Treatment:

Drug: glibenclamide

Placebo

Placebo Comparator group

Description:

2\. Stage 2, Safety/Efficacy: This part of the study occurs during weeks 2-13, in 3 successive blocks of 4 weeks each. During this stage, group assignments are randomized, and subjects are blinded as to test-drug vs. placebo. Depending on group assignment, exposure to test-drug may occur early (week-2) or later (week-6). In both groups, exposure to placebo occurs for 4 weeks and exposure to drug occurs for 8 successive weeks.

Treatment:

Drug: Placebo