Clinical trial NCT02771574: Efficacy, Tolerability and Pharmacokinetics of Subcutaneous Exendin (9-39) in Patients With Post Bariatric Hypoglycemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Post Bariatric Hypoglycemia
Keywords: Bariatric surgery complications
Glucose Metabolism Disorders
Exendin (9-39)
GLP-1
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Eiger BioPharmaceuticals
First posted: 2016-05-13
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Nadir Glucose
timeFrame: Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required)
Secondary outcomes:
measure: Change in Composite Symptom Score as a Measure of Treatment Effect
timeFrame: Baseline, Day 3
measure: Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co)
timeFrame: Day 3 (Predose)
measure: Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax)
timeFrame: Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
measure: Pharmacokinetics of Subcutaneous Avexitide: Time of Maximum Plasma Concentration (Tmax)
timeFrame: Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
measure: Pharmacokinetics of Subcutaneous Avexitide: Area Under the Plasma Concentration Versus Time Curve (AUC)
timeFrame: Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Clinical Assistant Professor
name: Marilyn Tan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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/dom.14048. Epub 2020 May 4.