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

Tracey McLaughlin

Status and phase: Completed; Phase 1

Conditions: Hyperinsulinemia Hypoglycemia

Treatments: Drug: Exendin (9-39)

Study type: Interventional

Funder types: Other

Identifiers

NCT02996812

34054

Details and patient eligibility

About

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.

Full 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.

Enrollment: 9 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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9 participants in 4 patient groups

Dose A

Active Comparator group

Description:

Subcutaneous injection of Dose A of Exendin (9-39)

Treatment:

Drug: Exendin (9-39)

Dose B

Active Comparator group

Description:

Subcutaneous injection of Dose B of Exendin (9-39)

Treatment:

Drug: Exendin (9-39)

Dose C

Active Comparator group

Description:

Subcutaneous injection of Dose C of Exendin (9-39)

Treatment:

Drug: Exendin (9-39)

Dose D

Active Comparator group

Description:

Subcutaneous injection of Dose D of Exendin (9-39)

Treatment:

Drug: Exendin (9-39)