Glucagon Ready to Use (RTU) in Subjects With Hyperinsulinemic Hypoglycemia After Bariatric Surgery

Sponsor

Xeris Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03770637

Collaborator

(none)

Enrollment

Locations

Arms

9.6

Actual Duration (Months)

2.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperinsulinemic Hypoglycemia	Drug: Glucagon RTU Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

A randomized, placebo-controlled, double-blind, two-treatment, 2-period, crossover in-patient phase followed by a placebo-controlled, double-blind, parallel two-treatment outpatient stage..A randomized, placebo-controlled, double-blind, two-treatment, 2-period, crossover in-patient phase followed by a placebo-controlled, double-blind, parallel two-treatment outpatient stage..

Masking:

Double (Participant, Investigator)

Masking Description:

The sponsor, investigators/staff and subjects will be blinded to treatment assignment. Active study drug and placebo have the identical appearance (i.e., clear, colorless liquid), and both will be provided in identical vials with blinded labeling that does not reveal the contents of the vial.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 10, 2019

Actual Primary Completion Date :

Feb 26, 2020

Actual Study Completion Date :

Feb 26, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glucagon RTU (glucagon injection) Glucagon Ready-to-Use (RTU); 60 μL injection (0.3 mg glucagon)	Drug: Glucagon RTU Glucagon RTU is a sterile subcutaneous injectable non-aqueous solution formulation supplied in a vial and administered via syringe. Other Names: glucagon
Placebo Comparator: Placebo Non-active vehicle for Glucagon RTU; 60 μL injection	Other: Placebo The placebo is a non-active version of Glucagon RTU formulation, containing the same solvent and excipients (i.e., vehicle).

Arm

Intervention/Treatment

Experimental: Glucagon RTU (glucagon injection)

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

Drug: Glucagon RTU

Glucagon RTU is a sterile subcutaneous injectable non-aqueous solution formulation supplied in a vial and administered via syringe.

Other Names:

glucagon

Placebo Comparator: Placebo

Non-active vehicle for Glucagon RTU; 60 μL injection

Other: Placebo

The placebo is a non-active version of Glucagon RTU formulation, containing the same solvent and excipients (i.e., vehicle).

Outcome Measures

Primary Outcome Measures

Blood glucose recovery: CRC [At 15 minutes following administration of study drug]
Number of subjects with blood glucose > 70 mg/dL
Blood glucose recovery: Out-patient [At 15 minutes following administration of study drug]
Frequency of blood glucose > 70 mg/dL

Secondary Outcome Measures

Symptomatic Recovery: CRC [At 15, 30, and 60 minutes following administration of study drug]
Change from Baseline in Hypoglycemia Symptoms
Incidence of severe hypoglycemia: CRC [At 0-240 minutes following administration of study drug]
Number of subjects requiring external assistance to treat hypoglycemia
Incidence of severe hypoglycemia: Out-patient [During 12 weeks of out-patient treatment]
Frequency of external assistance to treat postprandial hypoglycemia
Incidence of serious hypoglycemia: CRC [At 0-240 minutes following administration of study drug]
Number of subjects with blood glucose < 54 mg/dL
Incidence of serious hypoglycemia: Out-patient [During 12 weeks of out-patient treatment]
Frequency of postprandial blood glucose < 54 mg/dL
Hypoglycemia Fear Scale [During 12 weeks of out-patient treatment]
Change from Baseline in Hypoglycemia Fear Scale (HFS-2) Scores. The HFS-2 consists of two domains, Behavior, which has 15 questions, and Worry, which has 18 questions. Each question is assessed on a 5-point scale from 0=Never to 4=Almost Always. Lower scores indicate less fear of hypoglycemia, while higher scores indicate a greater level of fear.
EuroQol Health Questionnaire (EQ-5D) [During 12 weeks of out-patient treatment]
Change from Baseline in EQ-5D Score. This is a health assessment questionnaire with three domains. The first two domains of pain/discomfort and anxiety/depression are scored on a 5-point scale from 1=no pain/discomfort; not anxious or depressed to 5=extreme pain or discomfort; extremely anxious or depressed. For these two domains, lower scores indicate less pain/discomfort or anxiety/depression, while higher scores indicate increasing levels of pain/discomfort or anxiety/depression. The third domain of Health is assessed with a series of 5 visual analog scales, each scored from 0-100. On these VAS scales, high scores indicate better health, while low scores indicate worse health.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
Body mass index (BMI) ≤ 40 kg/m2
Willingness to follow all study procedures, including attending all clinic visits and self-administering blinded study drug at home for 12 weeks
Understands the study procedures, alternative treatment available, and risks involved with the study, and he/she voluntarily agrees to participate by giving written informed consent
Women of childbearing potential must have a negative urine pregnancy test and agree to use contraception and refrain from breast-feeding during the study and for at least 15 days after participating in the study.

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
Seizure disorder (other than with suspected or documented hypoglycemia).
Active malignancy, except for basal or squamous cell skin cancers
Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease)
Major surgical operation within 30 days prior to screening
Hematocrit ≤ 30%
Bleeding disorder, treatment with warfarin, or platelet count < 50,000 /mm3
Active alcohol abuse or substance abuse (per investigator assessment)
Current chronic administration of oral or parenteral corticosteroids, however topical, intraarticular, and inhaled corticosteroids are allowed
Use of an investigational drug within 15 days or 5 half-lives, whichever is longer, prior to screening
Member of a special vulnerable populations such as pregnant women, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable
Any other medical condition or finding that in the opinion of the investigator or sponsor, would compromise the safety of the subject or compromise the integrity of the study data

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado-Denver	Aurora	Colorado	United States	80045
2	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
3	Joslin Diabetes Center	Boston	Massachusetts	United States	02215
4	Mayo Clinic- Rochester	Rochester	Minnesota	United States	55905
5	Duke Early Phase Clinical Research	Durham	North Carolina	United States	27701