A Phase 2 Multi-Ascending Dose Trial to Assess the Efficacy, Tolerability and Pharmacokinetic Profile of Exendin (9-39) in Patients With Post-bariatric Hyperinsulinemic Hypoglycemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Nadir Glucose
研究概览
简要总结
This study is designed to evaluate the efficacy, safety and pharmacokinetics of subcutaneous exendin (9-39) in subjects with post-bariatric hypoglycemia. Development of this subcutaneous formulation of exendin (9-39) would represent a targeted therapeutic approach for this rare disease with unmet clinical need.
详细描述
Post-Bariatric Hypoglycemia (PBH) is a rare, but increasingly reported disease occurring after bariatric surgery, characterized by severe hypoglycemic episodes accompanied by symptoms of hypoglycemia. At the moment, no medical therapies have been developed for this disorder, but the clinical need is great. The major contributory factor is thought to be an exaggerated secretion of glucagon-like peptide-1 (GLP-1) due to altered nutrient transit after bariatric surgery. GLP-1 is an incretin hormone secreted primarily by the distal ileum that contributes to postprandial glucose regulation. Exendin (9-39) is a specific GLP-1 receptor antagonist, that when given via continuous IV infusion, has been shown to effectively prevent postprandial hypoglycemia and reduce symptoms of hypoglycemia in patients with PBH. This study is designed to assess the efficacy, safety and pharmacokinetic profile of a novel subcutaneous formulation of exendin (9-39).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Post-bariatric surgery more than 6 months prior to signing the informed consent
- •Reported history of Whipple's triad: the occurrence of hypoglycemic symptoms associated with a capillary blood glucose of ≤55 mg/dL, and resolution with glucose or carbohydrate administration.
- •Symptomatic hypoglycemia during the baseline/screening oral glucose tolerance test (OGTT), as defined by the presence of plasma glucose ≤55 mg/dL with concomitant autonomic and/or neuroglycopenic symptoms.
排除标准
- •Patients currently using sulfonylureas or other medications that may interfere with glucose metabolism within 5 half-lives of drug.
- •Participation in any clinical investigation within 4 weeks prior to dosing
- •History of or current insulinoma
- •Active infection or significant acute illness within 2 weeks prior to dosing
- •Female patients who are pregnant or lactating
- •Women of childbearing potential and not utilizing effective contraceptive methods
- •Inadequate end organ function
研究组 & 干预措施
Part A: Lyo avexitide 0.05 mg/kg
Participants will receive lyophilized avexitide (Lyo avexitide) twice daily for 3 days
干预措施: Lyo avexitide (Drug)
Part A: Lyo avexitide 0.15 mg/kg
Participants will receive Lyo avexitide twice daily for 3 days
干预措施: Lyo avexitide (Drug)
Part A: Lyo avexitide 0.35 mg/kg
Participants will receive Lyo avexitide twice daily for 3 days
干预措施: Lyo avexitide (Drug)
Part A: Lyo avexitide 0.46 mg/kg
Participants will receive Lyo avexitide twice daily for 3 days
干预措施: Lyo avexitide (Drug)
Part B: Liq avexitide 0.38 (±0.03) mg/kg
Participants will receive liquid avexitide (Liq avexitide) twice daily for 3 days
干预措施: Liq avexitide (Drug)
结局指标
主要结局
Nadir Glucose
时间窗: Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required)
Nadir glucose at baseline and at Day 3 of treatment during oral glucose tolerance test (OGTT).
次要结局
- Change in Composite Symptom Score as a Measure of Treatment Effect(Baseline, Day 3)
- Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co)(Day 3 (Predose))
- Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax)(Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose))
- Pharmacokinetics of Subcutaneous Avexitide: Time of Maximum Plasma Concentration (Tmax)(Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose))
- Pharmacokinetics of Subcutaneous Avexitide: Area Under the Plasma Concentration Versus Time Curve (AUC)(Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose))
研究者
Tracey McLaughlin
Associate Professor of Medicine (Endocrinology)
Stanford University