Avexitide Safety and Efficacy to Treat Acquired Hyperinsulinemic Hypoglycemia

Study Overview
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Brief Summary
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The primary goal of this study is to evaluate the safety and efficacy of two different dosing regimens of an investigational drug called Avexitide in treating low blood sugar in patients with Acquired Hyperinsulinemic Hypoglycemia.

Official Title
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A Phase 2, Open-Label, Cross-over Study to Assess the Safety and Efficacy of Avexitide in Acquired Hyperinsulinemic Hypoglycemia

Conditions
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Acquired Hyperinsulinemic Hypoglycemia

Intervention / Treatment
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* Drug: Avexitide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of bariatric or upper-gastrointestinal surgery (RYGB, VSG, gastrectomy, esophagectomy, or Nissen fundoplication) at least 12 months prior to the start of Screening History of recurrent hypoglycemia occurring after bariatric or upper-GI surgery, as documented in the medical record. Body mass index (BMI) of up to 40 kg/m2 If female, must not be breastfeeding and must have a negative urine pregnancy test result Exclusion Criteria: Major surgery within 6 months before randomization. History of or current hyperinsulinism other than Acquired Hyperinsulinism (e.g., insulin autoimmune hypoglycemia). Use of agents that may interfere with glucose metabolism

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avexitide 45 mg twice daily then avexitide 90 mg once daily<br>Patients will receive one of the two dosing regimens of avexitide for 14 days followed by the other dosing regimen of avextide for 14 days | Drug: Avexitide<br>* Avexitide (exendin 9-39) is a competitive antagonist of GLP-1 at its receptor<br>|
| Experimental: Avexitide 45 mg once daily then avexitide 90 mg twice daily<br>Patients will receive one of the two dosing regimens of avexitide for 14 days followed by the other dosing regimen of avextide for 14 days | Drug: Avexitide<br>* Avexitide (exendin 9-39) is a competitive antagonist of GLP-1 at its receptor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diurnal Level 2 Hypoglycemia Events (ADA, <54 mg/dL) as Measured by CGM in Patients With Severe Hyperinsulinemic Hypoglycemia (HH) | Level 2 hypoglycemia events (ADA, <54 mg/dL) as measured by CGM and defined as the number of events captured by CGM with glucose measures <54 mg/dL during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. | Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Level 2 Hypoglycemia (ADA, <54 mg/dL) as Measured by SMBG | Distinct episodes of Level 2 hypoglycemia (SMBG glucose <54 mg/dL), divided by number of days for run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. | Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days) | 
| Rate of Level 3 Hypoglycemia | Severe events during each treatment period characterized by altered mental and/or physical functioning that requires assistance from another person for recovery; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. This would apply regardless of whether a patient actually received external assistance. | Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days) | 
| Percent Time in Level 2 Hypoglycemia (<54 mg/dL) as Measured by CGM (Diurnal Time) | Percentage of time in level 2 hypoglycemia (<54mg/dL by CGM) during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. | Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days) | 
| Percent Time in Level 1 Hypoglycemia (<70 mg/dL) as Measured by CGM (Diurnal Time) | Percentage of time in level 1 hypoglycemia (<70mg/dL by CGM) during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. | Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days) | 
| Postprandial Glycemia During Standardized Mixed Meal Consumption | Change from Baseline in glycemia During Standardized Mixed Meal Consumption | 3 Hours Following Standardized Liquid Meal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post Bariatric Hypoglycemia, avexitide, Post-Bariatric Hypoglycemia, Post-gastrectomy hypoglycemia, Post gastrectomy hypoglycemia, Post-esophagectomy hypoglycemia, Post esophagectomy hypoglycemia, Post-Nissen Fundoplication hypoglycemia, Post Nissen Fundoplication hypoglycemia, Exendin (9-39), Exendin 9-39