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

October 19, 2020 updated by: Tracey McLaughlin

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: Lyo avexitide 0.05 mg/kg
Participants will receive lyophilized avexitide (Lyo avexitide) twice daily for 3 days
Drug: Lyo avexitide
Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc)
Other Names:
  • Exendin (9-39)
Experimental: Part A: Lyo avexitide 0.15 mg/kg
Participants will receive Lyo avexitide twice daily for 3 days
Drug: Lyo avexitide
Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc)
Other Names:
  • Exendin (9-39)
Experimental: Part A: Lyo avexitide 0.35 mg/kg
Participants will receive Lyo avexitide twice daily for 3 days
Drug: Lyo avexitide
Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc)
Other Names:
  • Exendin (9-39)
Experimental: Part A: Lyo avexitide 0.46 mg/kg
Participants will receive Lyo avexitide twice daily for 3 days
Drug: Lyo avexitide
Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc)
Other Names:
  • Exendin (9-39)
Experimental: Part B: Liq avexitide 0.38 (±0.03) mg/kg
Participants will receive liquid avexitide (Liq avexitide) twice daily for 3 days
Drug: Liq avexitide
Liquid avexitide (Liq avexitide) administered subcutaneously (sc)
Other Names:
  • Exendin (9-39)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nadir Glucose
Time Frame: Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required)
Nadir glucose at baseline and at Day 3 of treatment during oral glucose tolerance test (OGTT).
Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Composite Symptom Score as a Measure of Treatment Effect
Time Frame: Baseline, Day 3
Symptoms of hypoglycemia were assessed using the Edinburgh Hypoglycemia Symptom Scale that measures the intensity of 13 commonly experienced hypoglycemic symptoms, each severity graded on a 6-point Likert scale (0 = not present, 5 = severe). Scores are summed for a composite score ranging from 0 to 65, with higher scores corresponding to more severe hypoglycemia symptoms.
Baseline, Day 3
Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co)
Time Frame: Day 3 (Predose)
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Day 3 (Predose)
Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax)
Time Frame: Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Pharmacokinetics of Subcutaneous Avexitide: Time of Maximum Plasma Concentration (Tmax)
Time Frame: Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Pharmacokinetics of Subcutaneous Avexitide: Area Under the Plasma Concentration Versus Time Curve (AUC)
Time Frame: Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tracey McLaughlin

Collaborators

Eiger BioPharmaceuticals

Investigators

  • Principal Investigator: Marilyn Tan, MD, Clinical Assistant Professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2016

Primary Completion (Actual)

June 1, 2017

Study Completion (Actual)

June 1, 2017

Study Registration Dates

First Submitted

May 6, 2016

First Submitted That Met QC Criteria

May 10, 2016

First Posted (Estimate)

May 13, 2016

Study Record Updates

Last Update Posted (Actual)

November 13, 2020

Last Update Submitted That Met QC Criteria

October 19, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 36673

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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