Efficacy, Tolerability and Pharmacokinetics of Subcutaneous Exendin (9-39) in Patients With Post Bariatric Hypoglycemia

Tracey McLaughlin19 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Post Bariatric Hypoglycemia

Interventions

Lyo avexitideDRUG

Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc)

Liq avexitideDRUG

Liquid avexitide (Liq avexitide) administered subcutaneously (sc)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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

Locations (1)

Stanford University School of Medicine

Stanford, California, United States

Outcomes

Primary Outcomes

Nadir Glucose

Nadir glucose at baseline and at Day 3 of treatment during oral glucose tolerance test (OGTT).

Time frame: Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required)

Secondary Outcomes

Change in Composite Symptom Score as a Measure of Treatment Effect

Symptoms of hypoglycemia were assessed using the Edinburgh Hypoglycemia Symptom Scale that measures the intensity of 13 commonly experienced hypoglycemic symptoms, each severity graded on a 6-point Likert scale (0 = not present, 5 = severe). Scores are summed for a composite score ranging from 0 to 65, with higher scores corresponding to more severe hypoglycemia symptoms.

Time frame: Baseline, Day 3

Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co)

Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.

Time frame: Day 3 (Predose)

Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax)

Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.

Time frame: 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)

Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.

Time frame: 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)

Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.

Data from ClinicalTrials.gov

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