A Phase 2, Interventional, Randomized, Double-Blind, Placebo-Controlled Pilot Study of Glucagon RTU in Subjects Who Experience Hyperinsulinemic Hypoglycemia After Bariatric Surgery

Xeris Pharmaceuticals5 sites in 1 country14 target enrollmentMay 10, 2019

ConditionsHyperinsulinemic Hypoglycemia

InterventionsGlucagon RTU Placebo

Overview

Phase: Phase 2
Intervention: Glucagon RTU
Conditions: Hyperinsulinemic Hypoglycemia
Sponsor: Xeris Pharmaceuticals
Enrollment: 14
Locations: 5
Primary Endpoint: Blood glucose recovery: Out-patient
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a double-blind, placebo-controlled Phase 2 study to assess the efficacy, safety and tolerability of Glucagon RTU when administered to subjects with a history of bariatric surgery during episodes of post-postprandial hypoglycemia. Twelve eligible subjects will be randomly assigned to receive Glucagon RTU or placebo at the first of two clinical research center (CRC) visits, followed by the other treatment at the second CRC visit. Subjects will be randomly assigned to either Glucagon RTU or Placebo for the duration of a 12-week Outpatient Stage. A follow-up safety assessment visit will occur 14 to 28 days after a subject's last dose of study drug.

Registry

clinicaltrials.gov

Start Date

May 10, 2019

End Date

February 26, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

Xeris Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female
•Aged 18 to 75 years of age, inclusive
•Symptoms of hypoglycemia that developed after bariatric surgery (Roux-en-Y gastric bypass \[RYGB\] only) in the absence of antidiabetic medications
•History of bariatric surgery (RYGB only), at least 6 months prior to screening
•Whipple's triad
•Ability to both experience and recognize hypoglycemic awareness.
•Documented glucose levels \< 54 mg/dL when experiencing symptoms suggestive of hypoglycemia
•Relief of hypoglycemia symptoms when the glucose is raised to normal
•Diagnosis of post-bariatric hypoglycemia (PBH) by a physician, requiring intervention such as intake of oral carbohydrates. This diagnosis includes documentation of endogenous hyperinsulinism in the presence of low plasma glucose.
•In subjects with medical history of diabetes, medical documentation of postoperative remission of diabetes mellitus (fasting glucose \< 110 mg/dL), and HbA1c \< 6% (or 42 mmol/mL) with all previous antidiabetic medication discontinued for at least 6 months before screening.

Exclusion Criteria

•Documented hypoglycemia occurring in the fasting state (\> 12 hours fast) within 12 months of study entry
•Hypoglycemic unawareness as evidenced by a Gold Scale score \> 4 at screening
•Early Dumping Syndrome
•Known insulinoma or adrenal insufficiency
•Active treatment with any insulin/insulin secretagogues, or other diabetes medications except for acarbose and glucagon-like peptide 1 (GLP-1) analogues
•Chronic kidney disease Stage 4 or 5 or an estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min/1.73 m2 at screening
•Hepatic disease, including serum alanine aminotransferase or aspartate aminotransferase ≥ 3 times the upper limit of normal (ULN); hepatic synthetic insufficiency as defined as serum albumin \< 3.0 g/dL
•Congestive heart failure, New York Heart Association Class III or IV
•History of myocardial infarction, unstable angina, or revascularization within 6 months prior to screening.
•History of a cerebrovascular accident within 6 months prior to screening or with major neurological deficits

Arms & Interventions

Glucagon RTU (glucagon injection)

Glucagon Ready-to-Use (RTU); 60 μL injection (0.3 mg glucagon)

Intervention: Glucagon RTU

Placebo

Non-active vehicle for Glucagon RTU; 60 μL injection

Intervention: Placebo

Outcomes

Primary Outcomes

Blood glucose recovery: Out-patient

Time Frame: At 15 minutes following administration of study drug

Frequency of blood glucose \> 70 mg/dL

Blood glucose recovery: CRC

Time Frame: At 15 minutes following administration of study drug

Number of subjects with blood glucose \> 70 mg/dL

Secondary Outcomes

Symptomatic Recovery: CRC(At 15, 30, and 60 minutes following administration of study drug)
Incidence of severe hypoglycemia: Out-patient(During 12 weeks of out-patient treatment)
Incidence of severe hypoglycemia: CRC(At 0-240 minutes following administration of study drug)
Incidence of serious hypoglycemia: CRC(At 0-240 minutes following administration of study drug)
Incidence of serious hypoglycemia: Out-patient(During 12 weeks of out-patient treatment)
Hypoglycemia Fear Scale(During 12 weeks of out-patient treatment)
EuroQol Health Questionnaire (EQ-5D)(During 12 weeks of out-patient treatment)