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

Post Bariatric Hypoglycemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02771574
• Other study ID #: 36673
• Status: Completed
• Phase: Phase 2
• Start date: May 2016
• Est. completion date: June 2017

Study information

• Verified date: October 2020
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypoglycemia
• Post Bariatric Hypoglycemia

Intervention

Drug:
• Lyo avexitide
Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc)
• Liq avexitide
Liquid avexitide (Liq avexitide) administered subcutaneously (sc)

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Tracey McLaughlin	Eiger BioPharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (1)

Tan M, Lamendola C, Luong R, McLaughlin T, Craig C. Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9-39) for treatment of post-bariatric hypoglycaemia. Diabetes Obes Metab. 2020 Aug;22(8):1406-1416. doi: 10.1111/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nadir Glucose	Nadir glucose at baseline and at Day 3 of treatment during oral glucose tolerance test (OGTT).	Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required)
Secondary	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.	Baseline, Day 3
Secondary	Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co)	Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.	Day 3 (Predose)
Secondary	Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax)	Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.	Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Secondary	Pharmacokinetics of Subcutaneous Avexitide: Time of Maximum Plasma Concentration (Tmax)	Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.	Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Secondary	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.	Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)