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

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ClinicalTrials.gov Identifier: NCT02771574
Recruitment Status : Completed
First Posted : May 13, 2016
Results First Posted : August 14, 2020
Last Update Posted : November 13, 2020
Sponsor:
Collaborator:
Eiger BioPharmaceuticals
Information provided by (Responsible Party):
Tracey McLaughlin, Stanford University

Study Description
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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.

Condition or disease Intervention/treatment Phase
Post Bariatric Hypoglycemia Drug: Lyo avexitide Drug: Liq avexitide Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
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 Start Date : May 2016
Actual Primary Completion Date : June 2017
Actual Study Completion Date : June 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia

Arms and Interventions
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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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Exendin (9-39)


Outcome Measures
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Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02771574


Locations
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United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Tracey McLaughlin
Eiger BioPharmaceuticals
Investigators
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Principal Investigator: Marilyn Tan, MD Clinical Assistant Professor
  Study Documents (Full-Text)

Documents provided by Tracey McLaughlin, Stanford University:
Statistical Analysis Plan  [PDF] July 20, 2020
Study Protocol  [PDF] May 6, 2016

More Information
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Publications of Results:

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Responsible Party: Tracey McLaughlin, Associate Professor of Medicine (Endocrinology), Stanford University
ClinicalTrials.gov Identifier: NCT02771574    
Other Study ID Numbers: 36673
First Posted: May 13, 2016    Key Record Dates
Results First Posted: August 14, 2020
Last Update Posted: November 13, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tracey McLaughlin, Stanford University:
Bariatric surgery complications
Glucose Metabolism Disorders
Exendin (9-39)
GLP-1
Additional relevant MeSH terms:
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Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases