Evaluation of Single Ascending Doses of Subcutaneous Exendin 9-39 in Patients With Post-Bariatric Hypoglycemia

Phase 1

Completed

• Conditions: Hyperinsulinemia Hypoglycemia
• Interventions: Drug: Exendin (9-39)

• Registration Number: NCT02996812
• Lead Sponsor: Tracey McLaughlin

Brief Summary

This study is designed to evaluate the safety, efficacy, and pharmacokinetic profile of single ascending doses of exendin 9-39 administered by subcutaneous route in subjects with post-bariatric hypoglycemia.

Detailed Description

Post-Bariatric Hypoglycemia (PBH) is a debilitating rare disease afflicting 0.2-6.9% of post-bariatric patients, characterized by repeated severe hypoglycemic episodes with neuroglycopenic symptoms and marked disability. There are no effective medical therapies.

While the cause is not known, exaggerated postprandial secretion of glucagon-like peptide-1 (GLP-1) as a result of altered nutrient transit likely plays a major role. GLP-1 is an incretin hormone secreted primarily by the distal ileum that contributes to postprandial glucose regulation. Exendin 9-39 (Ex9) is a specific GLP-1 receptor antagonist, that when given via continuous IV infusion, has been shown to effectively prevent postprandial hypoglycemia in patients with PBH. Subcutaneous (SC) injection of Ex9 may represent a safe, effective and practical therapeutic approach to treating PBH.

Study Timeline

• Study Start: 2015-04
• Primary Completion: 2016-08
• Study Completion: 2016-08
• Study First Submitted: 2016-12-15
• Study First Submitted QC: 2016-12-15
• Study First Posted: 2016-12-19
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-02
• Last Update Posted: 2024-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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 blood glucose of ≤55 mg/dL, and resolution with glucose or carbohydrate administration.
• Symptomatic hypoglycemia during the baseline/screening 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose B	Exendin (9-39)	Subcutaneous injection of Dose B of Exendin (9-39)
Dose A	Exendin (9-39)	Subcutaneous injection of Dose A of Exendin (9-39)
Dose D	Exendin (9-39)	Subcutaneous injection of Dose D of Exendin (9-39)
Dose C	Exendin (9-39)	Subcutaneous injection of Dose C of Exendin (9-39)

Primary Outcome Measures

Name	Time	Method
Treatment effect on plasma glucose	0-180 minutes following initiation of oral glucose tolerance test (OGTT) conducted after treatment.	Magnitude of plasma glucose nadir during repeat OGTT after treatment

Secondary Outcome Measures

Name	Time	Method
Treatment effect on symptoms of hypoglycemia	0-180 minutes following initiation of OGTT	Response rate in symptom score during repeat OGTT after treatment.

Trial Locations

Locations (1)

Stanford University School of Medicine; 🇺🇸 Stanford, California, United States