Glucagon Ready to Use (RTU) in Subjects With Hyperinsulinemic Hypoglycemia After Bariatric Surgery
Primary Purpose
Hyperinsulinemic Hypoglycemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Glucagon RTU
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hyperinsulinemic Hypoglycemia focused on measuring glucagon, post-bariatric hypoglycemia
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.
- 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
Sites / Locations
- University of Colorado-Denver
- Johns Hopkins Hospital
- Joslin Diabetes Center
- Mayo Clinic- Rochester
- Duke Early Phase Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Glucagon RTU (glucagon injection)
Placebo
Arm Description
Glucagon Ready-to-Use (RTU); 60 μL injection (0.3 mg glucagon)
Non-active vehicle for Glucagon RTU; 60 μL injection
Outcomes
Primary Outcome Measures
Blood glucose recovery: CRC
Number of subjects with blood glucose > 70 mg/dL
Blood glucose recovery: Out-patient
Frequency of blood glucose > 70 mg/dL
Secondary Outcome Measures
Symptomatic Recovery: CRC
Change from Baseline in Hypoglycemia Symptoms
Incidence of severe hypoglycemia: CRC
Number of subjects requiring external assistance to treat hypoglycemia
Incidence of severe hypoglycemia: Out-patient
Frequency of external assistance to treat postprandial hypoglycemia
Incidence of serious hypoglycemia: CRC
Number of subjects with blood glucose < 54 mg/dL
Incidence of serious hypoglycemia: Out-patient
Frequency of postprandial blood glucose < 54 mg/dL
Hypoglycemia Fear Scale
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03770637
Brief Title
Glucagon Ready to Use (RTU) in Subjects With Hyperinsulinemic Hypoglycemia After Bariatric Surgery
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
May 10, 2019 (Actual)
Primary Completion Date
February 26, 2020 (Actual)
Study Completion Date
February 26, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xeris Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperinsulinemic Hypoglycemia
Keywords
glucagon, post-bariatric hypoglycemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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..
Masking
ParticipantInvestigator
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.
Allocation
Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Glucagon RTU (glucagon injection)
Arm Type
Experimental
Arm Description
Glucagon Ready-to-Use (RTU); 60 μL injection (0.3 mg glucagon)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Non-active vehicle for Glucagon RTU; 60 μL injection
Intervention Type
Drug
Intervention Name(s)
Glucagon RTU
Other Intervention Name(s)
glucagon
Intervention Description
Glucagon RTU is a sterile subcutaneous injectable non-aqueous solution formulation supplied in a vial and administered via syringe.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
The placebo is a non-active version of Glucagon RTU formulation, containing the same solvent and excipients (i.e., vehicle).
Primary Outcome Measure Information:
Title
Blood glucose recovery: CRC
Description
Number of subjects with blood glucose > 70 mg/dL
Time Frame
At 15 minutes following administration of study drug
Title
Blood glucose recovery: Out-patient
Description
Frequency of blood glucose > 70 mg/dL
Time Frame
At 15 minutes following administration of study drug
Secondary Outcome Measure Information:
Title
Symptomatic Recovery: CRC
Description
Change from Baseline in Hypoglycemia Symptoms
Time Frame
At 15, 30, and 60 minutes following administration of study drug
Title
Incidence of severe hypoglycemia: CRC
Description
Number of subjects requiring external assistance to treat hypoglycemia
Time Frame
At 0-240 minutes following administration of study drug
Title
Incidence of severe hypoglycemia: Out-patient
Description
Frequency of external assistance to treat postprandial hypoglycemia
Time Frame
During 12 weeks of out-patient treatment
Title
Incidence of serious hypoglycemia: CRC
Description
Number of subjects with blood glucose < 54 mg/dL
Time Frame
At 0-240 minutes following administration of study drug
Title
Incidence of serious hypoglycemia: Out-patient
Description
Frequency of postprandial blood glucose < 54 mg/dL
Time Frame
During 12 weeks of out-patient treatment
Title
Hypoglycemia Fear Scale
Description
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.
Time Frame
During 12 weeks of out-patient treatment
Title
EuroQol Health Questionnaire (EQ-5D)
Description
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.
Time Frame
During 12 weeks of out-patient treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
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
Facility Information:
Facility Name
University of Colorado-Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Joslin Diabetes Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Mayo Clinic- Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Duke Early Phase Clinical Research
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27701
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Glucagon Ready to Use (RTU) in Subjects With Hyperinsulinemic Hypoglycemia After Bariatric Surgery
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