Safety and Efficacy of Exendin 9-39 in Patients With Postbariatric Hypoglycemia (PREVENT)

• ClinicalTrials.gov Identifier: NCT03373435
• Recruitment Status: Completed
• First Posted: December 14, 2017
• Last Update Posted: February 6, 2020
• Sponsor: Eiger BioPharmaceuticals
• Information provided by (Responsible Party): Eiger BioPharmaceuticals

Study Description

Brief Summary:

This clinical study will evaluate whether taking an investigational drug called exendin 9-39 is safe, well-tolerated, and helps to prevent low blood sugar in people who have had bariatric surgery and later develop a rare condition called postbariatric hypoglycemia (PBH).

Condition or disease	Intervention/treatment	Phase
Postbariatric Hypoglycemia	Drug: exendin 9-39; Other: Placebo	Phase 2

Detailed Description:

This is a Phase 2, multicenter, randomized, single-blind, placebo-controlled cross-over study in patients with refractory PBH.

Participants will be randomized and assigned in a 1:1 ratio to one of two treatment arms. All participants will receive 2 dosing regimens of exendin 9-39 and matching placebo self-administered via subcutaneous (SC) injection.

Participants will undergo in-clinic mixed meal tolerance test (MMTT) provocation with concomitant blood draws and symptom assessments.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized, Single-Blind, Placebo-Controlled Cross-over Study to Assess the Efficacy and Safety of Exendin 9-39 in Patients With Postbariatric Hypoglycemia
• Actual Study Start Date: March 19, 2018
• Actual Primary Completion Date: September 19, 2018
• Actual Study Completion Date: October 15, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment Group 1; patients will receive two dose regimens of exendin 9-39 and one placebo	Drug: exendin 9-39; Exendin 9-39 is a competitive antagonist of GLP-1 at its receptor.; Other Name: Glucagon-like peptide-1 (GLP-1) antagonist; Other: Placebo; Placebo solution is identical to the active drug product except for the absence of the active ingredient, Exendin 9-39.
Experimental: Treatment Group 2; patients will receive two dose regimens of exendin 9-39 and one placebo (in a different sequence than Treatment Group 1)	Drug: exendin 9-39; Exendin 9-39 is a competitive antagonist of GLP-1 at its receptor.; Other Name: Glucagon-like peptide-1 (GLP-1) antagonist; Other: Placebo; Placebo solution is identical to the active drug product except for the absence of the active ingredient, Exendin 9-39.

Outcome Measures

Primary Outcome Measures :

1. Postprandial Hypoglycemia [ Time Frame: 3 hours following a liquid meal ]
   Plasma glucose nadir occurring within 3 hours of MMTT
2. Incidence of treatment-emergent adverse events [ Time Frame: 6 weeks ]
   An adverse event can be any unfavorable and unintended sign, symptom, or disease that occurs during the study treatment periods.

Secondary Outcome Measures :

1. Severity score of postprandial neuroglycopenic signs and symptoms calculated from patients' responses to the Edinburgh Hypoglycemia Symptom Scale. (EHSS). [ Time Frame: 3 hours following a liquid meal ]
   Neuroglycopenic symptoms evaluated by the EHSS include blurred vision, confusion, drowsiness, speech difficulty, incoordination, dizziness, and inability to concentrate. Patients will complete the EHSS approximately every 30 minutes during each MMTT.
2. Postprandial hyperinsulinemia. [ Time Frame: 3 hours following a liquid meal ]
   Peak postprandial insulin concentration in response to MMTT

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Body mass index (BMI) of up to 40 kg/m2
• Roux-en-Y gastric bypass (RYGB) surgery performed ≥12 months prior
• Diagnosis of PBH
• At least 2 episodes during screening 2-week run-in phase of severe hypoglycemia

Exclusion Criteria:

• Other cause of endogenous hyperinsulinism other than PBH
• Metabolic or bariatric surgical procedure other than RYGB
• History of non-RYGB upper GI surgery
• Use of agents that may interfere with glucose metabolism

Contacts and Locations

Locations

United States, California

Stanford University

Palo Alto, California, United States, 94304

United States, Colorado

University of Colorado, Denver

Aurora, Colorado, United States, 80045

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

United States, North Carolina

Duke Early Phase Clinical Research

Durham, North Carolina, United States, 27710

United States, Wisconsin

University of Wisconsin

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Eiger BioPharmaceuticals

Investigators

• Study Director: Colleen Craig, MD; Eiger BioPharmaceuticals, Inc

More Information

• Responsible Party: Eiger BioPharmaceuticals
• ClinicalTrials.gov Identifier: NCT03373435
• Other Study ID Numbers: EIG-EXD-001
• First Posted: December 14, 2017
• Last Update Posted: February 6, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hypoglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Glucagon; Glucagon-Like Peptide 1; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Incretins