Avexitide Safety and Efficacy to Treat Acquired Hyperinsulinemic Hypoglycemia

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

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.

Study Overview

• Status: Completed
• Conditions: Acquired Hyperinsulinemic Hypoglycemia
• Intervention / Treatment: Drug: Avexitide

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Clinical and Translational Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Avexitide 45 mg twice daily then avexitide 90 mg once daily; 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; Avexitide (exendin 9-39) is a competitive antagonist of GLP-1 at its receptor
Experimental: Avexitide 45 mg once daily then avexitide 90 mg twice daily; 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; Avexitide (exendin 9-39) is a competitive antagonist of GLP-1 at its receptor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dr. Tracey McLaughlin, MD
• Collaborators: Eiger BioPharmaceuticals
• Investigators: Study Director: Marilyn Tan, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2021
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: October 27, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: 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
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Infant, Newborn, Diseases; Hyperinsulinism; Pancreatic Diseases; Hypoglycemia; Congenital Hyperinsulinism; Nesidioblastosis
• Other Study ID Numbers: 52880

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No