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

Tracey McLaughlin

Status and phase: Completed; Phase 2

Conditions: Post Bariatric Hypoglycemia

Treatments: Drug: Liq avexitide; Drug: Lyo avexitide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02771574

36673

Details and patient eligibility

About

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.

Full 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).

Enrollment: 19 patients

Sex: All

Ages: 18 to 70 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 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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19 participants in 5 patient groups

Part A: Lyo avexitide 0.05 mg/kg

Experimental group

Description:

Participants will receive lyophilized avexitide (Lyo avexitide) twice daily for 3 days

Treatment:

Drug: Lyo avexitide

Part A: Lyo avexitide 0.15 mg/kg

Experimental group

Description:

Participants will receive Lyo avexitide twice daily for 3 days

Treatment:

Drug: Lyo avexitide

Part A: Lyo avexitide 0.35 mg/kg

Experimental group

Description:

Participants will receive Lyo avexitide twice daily for 3 days

Treatment:

Drug: Lyo avexitide

Part A: Lyo avexitide 0.46 mg/kg

Experimental group

Description:

Participants will receive Lyo avexitide twice daily for 3 days

Treatment:

Drug: Lyo avexitide

Part B: Liq avexitide 0.38 (±0.03) mg/kg

Experimental group

Description:

Participants will receive liquid avexitide (Liq avexitide) twice daily for 3 days

Treatment:

Drug: Liq avexitide