A Pilot Study of the Pharmacodynamics and Clinical Effects of Oral Extended Release (OER) Glibenclamide in Multiple Sclerosis Patients With Neuropathic Pain
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Cmax
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
In stage 2, medication will be either placebo or treatment, blinded in appearance. Investigators will not be aware of placebo/treatment assignment.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of multiple sclerosis per the 2017 Revised McDonald Criteria
- •Score of ≥ 19 on the painDETECT questionnaire
排除标准
- •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
研究组 & 干预措施
oral extended release glibenclamide
- Stage 1, Pharmacokinetics/Pharmacodynamics: This will be a 5 day, unblinded evaluation while participants receive OER-glibenclamide
- 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.
干预措施: glibenclamide (Drug)
Placebo
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Cmax
时间窗: over 10 hours
maximum concentration
Safety
时间窗: Through week 13
Full reporting of any adverse events on study drug
Cmin
时间窗: Over 10 hours
Minimum concentration
AUC
时间窗: 10 hours
Area under curve
tmax
时间窗: 10 hours
time to maximum concentration
t 1/2
时间窗: 10 hours
time to 1/2 maximum concentration
blood glucose
时间窗: 10 hours
blood glucose during 10 hour pharmacokinetic measurements
次要结局
- Change in PROMIS Neuropathic Pain Scale Score(Through week 13)
- Change in the PROMISE Pain Interference Score(Through week 13)