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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Subcutaneous Injection of Exendin (9-39) in Subjects With Hyperinsulinemic Hypoglycemia Post-Bariatric Surgery

Conditions
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Hyperinsulinemia Hypoglycemia

Intervention / Treatment
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* Drug: Exendin (9-39)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dose A<br>Subcutaneous injection of Dose A of Exendin (9-39) | Drug: Exendin (9-39)<br> <br> |
| Active Comparator: Dose B<br>Subcutaneous injection of Dose B of Exendin (9-39) | Drug: Exendin (9-39)<br> <br> |
| Active Comparator: Dose C<br>Subcutaneous injection of Dose C of Exendin (9-39) | Drug: Exendin (9-39)<br> <br> |
| Active Comparator: Dose D<br>Subcutaneous injection of Dose D of Exendin (9-39) | Drug: Exendin (9-39)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment effect on plasma glucose | Magnitude of plasma glucose nadir during repeat OGTT after treatment | 0-180 minutes following initiation of oral glucose tolerance test (OGTT) conducted after treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment effect on symptoms of hypoglycemia | Response rate in symptom score during repeat OGTT after treatment. | 0-180 minutes following initiation of OGTT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-bariatric hypoglycemia, Non-insulinoma pancreatogenous hypoglycemia syndrome, Late dumping syndrome