Acquired Hyperinsulinemic Hypoglycemia
Conditions
Keywords
Post Bariatric Hypoglycemia, avexitide, Post-Bariatric Hypoglycemia, Post-gastrectomy hypoglycemia, Post gastrectomy hypoglycemia, Post-esophagectomy hypoglycemia, Post esophagectomy hypoglycemia, Post-Nissen Fundoplication hypoglycemia, Post Nissen Fundoplication hypoglycemia, Exendin (9-39), Exendin 9-39
Brief summary
The primary goal of this study is to evaluate the safety and efficacy of two different dosing regimens of an investigational drug called Avexitide in treating low blood sugar in patients with Acquired Hyperinsulinemic Hypoglycemia.
Interventions
DRUGAvexitide
Avexitide (exendin 9-39) is a competitive antagonist of GLP-1 at its receptor
Sponsors
Eiger BioPharmaceuticals
Dr. Tracey McLaughlin, MD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of bariatric or upper-gastrointestinal surgery (RYGB, VSG, gastrectomy, esophagectomy, or Nissen fundoplication) at least 12 months prior to the start of Screening * History of recurrent hypoglycemia occurring after bariatric or upper-GI surgery, as documented in the medical record. * Body mass index (BMI) of up to 40 kg/m2 * If female, must not be breastfeeding and must have a negative urine pregnancy test result
Exclusion criteria
* Major surgery within 6 months before randomization. * History of or current hyperinsulinism other than Acquired Hyperinsulinism (e.g., insulin autoimmune hypoglycemia). * Use of agents that may interfere with glucose metabolism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diurnal Level 2 Hypoglycemia Events (ADA, <54 mg/dL) as Measured by CGM in Patients With Severe Hyperinsulinemic Hypoglycemia (HH) | Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days) | Level 2 hypoglycemia events (ADA, \<54 mg/dL) as measured by CGM and defined as the number of events captured by CGM with glucose measures \<54 mg/dL during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postprandial Glycemia During Standardized Mixed Meal Consumption | 3 Hours Following Standardized Liquid Meal | Change from Baseline in glycemia During Standardized Mixed Meal Consumption |
| Rate of Level 2 Hypoglycemia (ADA, <54 mg/dL) as Measured by SMBG | Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days) | Distinct episodes of Level 2 hypoglycemia (SMBG glucose \<54 mg/dL), divided by number of days for run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. |
| Rate of Level 3 Hypoglycemia | Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days) | Severe events during each treatment period characterized by altered mental and/or physical functioning that requires assistance from another person for recovery; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. This would apply regardless of whether a patient actually received external assistance. |
| Percent Time in Level 2 Hypoglycemia (<54 mg/dL) as Measured by CGM (Diurnal Time) | Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days) | Percentage of time in level 2 hypoglycemia (\<54mg/dL by CGM) during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. |
| Percent Time in Level 1 Hypoglycemia (<70 mg/dL) as Measured by CGM (Diurnal Time) | Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days) | Percentage of time in level 1 hypoglycemia (\<70mg/dL by CGM) during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. |
Countries
United States
Participant flow
Pre-assignment details
25 participants entered a 14-day run-in (screening) period during which they wore the continuous glucose monitor (CGM). 17 participants who had at least 2 hypoglycemic events were randomized to a study arm.
Participants by arm
| Arm | Count |
|---|---|
| Avexitide 45 mg Twice Daily Then Avexitide 90 mg Once Daily Patients receive one of the two dosing regimens of avexitide for 14 days followed by the other dosing regimen of avextide for 14 days | 8 |
| Avexitide 90 mg Once Daily Then Avexitide 45 mg Twice Daily Patients receive one of the two dosing regimens of avexitide for 14 days followed by the other dosing regimen of avextide for 14 days | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Total | Avexitide 45 mg Twice Daily Then Avexitide 90 mg Once Daily | Avexitide 90 mg Once Daily Then Avexitide 45 mg Twice Daily |
|---|---|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 12.8 | 48.1 years STANDARD_DEVIATION 15.2 | 47.8 years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 6 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 5 Participants | 6 Participants |
| Region of Enrollment United States | 16 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 14 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 0 / 25 | 7 / 17 | 8 / 17 |
| serious Total, serious adverse events | 0 / 25 | 0 / 17 | 0 / 17 |
Outcome results
Primary
Diurnal Level 2 Hypoglycemia Events (ADA, <54 mg/dL) as Measured by CGM in Patients With Severe Hyperinsulinemic Hypoglycemia (HH)
Level 2 hypoglycemia events (ADA, \<54 mg/dL) as measured by CGM and defined as the number of events captured by CGM with glucose measures \<54 mg/dL during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days.
Time frame: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)
Population: Participants with no major protocol deviations who were allocated to treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avexitide 45 mg Twice Daily | Diurnal Level 2 Hypoglycemia Events (ADA, <54 mg/dL) as Measured by CGM in Patients With Severe Hyperinsulinemic Hypoglycemia (HH) | Run-in period | 5.2 events per 14 days | Standard Deviation 3.52 |
| Avexitide 45 mg Twice Daily | Diurnal Level 2 Hypoglycemia Events (ADA, <54 mg/dL) as Measured by CGM in Patients With Severe Hyperinsulinemic Hypoglycemia (HH) | Treatment period | 2.7 events per 14 days | Standard Deviation 2.15 |
| Avexitide 90 mg Once Daily | Diurnal Level 2 Hypoglycemia Events (ADA, <54 mg/dL) as Measured by CGM in Patients With Severe Hyperinsulinemic Hypoglycemia (HH) | Run-in period | 5.2 events per 14 days | Standard Deviation 3.52 |
| Avexitide 90 mg Once Daily | Diurnal Level 2 Hypoglycemia Events (ADA, <54 mg/dL) as Measured by CGM in Patients With Severe Hyperinsulinemic Hypoglycemia (HH) | Treatment period | 2.1 events per 14 days | Standard Deviation 2.99 |
Comparison: Within-group analysisp-value: 0.0028Mixed effects model
Comparison: Within-group analysisp-value: 0.0005Mixed effects model
Secondary
Percent Time in Level 1 Hypoglycemia (<70 mg/dL) as Measured by CGM (Diurnal Time)
Percentage of time in level 1 hypoglycemia (\<70mg/dL by CGM) during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days.
Time frame: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)
Population: Participants with no major protocol deviations who were allocated to treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avexitide 45 mg Twice Daily | Percent Time in Level 1 Hypoglycemia (<70 mg/dL) as Measured by CGM (Diurnal Time) | Run-in period | 4.20 percentage of time per 14 days | Standard Deviation 2.75 |
| Avexitide 45 mg Twice Daily | Percent Time in Level 1 Hypoglycemia (<70 mg/dL) as Measured by CGM (Diurnal Time) | Treatment period | 2.86 percentage of time per 14 days | Standard Deviation 1.54 |
| Avexitide 90 mg Once Daily | Percent Time in Level 1 Hypoglycemia (<70 mg/dL) as Measured by CGM (Diurnal Time) | Run-in period | 4.20 percentage of time per 14 days | Standard Deviation 2.75 |
| Avexitide 90 mg Once Daily | Percent Time in Level 1 Hypoglycemia (<70 mg/dL) as Measured by CGM (Diurnal Time) | Treatment period | 1.96 percentage of time per 14 days | Standard Deviation 1.63 |
Comparison: Between-group analysis of change from baselinep-value: 0.145t-test, 2 sided
Comparison: Within-group analysis of change from baselinep-value: 0.111t-test, 2 sided
Comparison: Within-group analysis of change from baselinep-value: 0.001t-test, 2 sided
Secondary
Percent Time in Level 2 Hypoglycemia (<54 mg/dL) as Measured by CGM (Diurnal Time)
Percentage of time in level 2 hypoglycemia (\<54mg/dL by CGM) during diurnal hours (8am-10pm) within the run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days.
Time frame: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)
Population: Participants with no major protocol deviations who were allocated to treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avexitide 45 mg Twice Daily | Percent Time in Level 2 Hypoglycemia (<54 mg/dL) as Measured by CGM (Diurnal Time) | Run-in period | 1.50 percentage of time per 14 days | Standard Deviation 1.32 |
| Avexitide 45 mg Twice Daily | Percent Time in Level 2 Hypoglycemia (<54 mg/dL) as Measured by CGM (Diurnal Time) | Treatment period | 0.96 percentage of time per 14 days | Standard Deviation 0.74 |
| Avexitide 90 mg Once Daily | Percent Time in Level 2 Hypoglycemia (<54 mg/dL) as Measured by CGM (Diurnal Time) | Run-in period | 1.50 percentage of time per 14 days | Standard Deviation 1.32 |
| Avexitide 90 mg Once Daily | Percent Time in Level 2 Hypoglycemia (<54 mg/dL) as Measured by CGM (Diurnal Time) | Treatment period | 0.48 percentage of time per 14 days | Standard Deviation 0.82 |
Comparison: Between-group analysis of change from baselinep-value: 0.161t-test, 2 sided
Comparison: Within-group analysis of change from baselinep-value: 0.201t-test, 2 sided
Comparison: Within-group analysis of change from baselinep-value: 0.001t-test, 2 sided
Secondary
Postprandial Glycemia During Standardized Mixed Meal Consumption
Change from Baseline in glycemia During Standardized Mixed Meal Consumption
Time frame: 3 Hours Following Standardized Liquid Meal
Population: Data were not collected for this outcome
Secondary
Rate of Level 2 Hypoglycemia (ADA, <54 mg/dL) as Measured by SMBG
Distinct episodes of Level 2 hypoglycemia (SMBG glucose \<54 mg/dL), divided by number of days for run-in period and respective treatment period; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days.
Time frame: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)
Population: Participants with no major protocol deviations who were allocated to treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avexitide 45 mg Twice Daily | Rate of Level 2 Hypoglycemia (ADA, <54 mg/dL) as Measured by SMBG | Run-in period | 2.7 episodes per 14 days | Standard Deviation 3.1 |
| Avexitide 45 mg Twice Daily | Rate of Level 2 Hypoglycemia (ADA, <54 mg/dL) as Measured by SMBG | Treatment period | 1.2 episodes per 14 days | Standard Deviation 1.4 |
| Avexitide 90 mg Once Daily | Rate of Level 2 Hypoglycemia (ADA, <54 mg/dL) as Measured by SMBG | Run-in period | 2.7 episodes per 14 days | Standard Deviation 3.1 |
| Avexitide 90 mg Once Daily | Rate of Level 2 Hypoglycemia (ADA, <54 mg/dL) as Measured by SMBG | Treatment period | 1.3 episodes per 14 days | Standard Deviation 3.7 |
Comparison: Within-group analysisp-value: 0.0027Mixed effects model
Comparison: Within-group analysisp-value: 0.0043Mixed effects model
Secondary
Rate of Level 3 Hypoglycemia
Severe events during each treatment period characterized by altered mental and/or physical functioning that requires assistance from another person for recovery; for each period data were collected for 14 days, then divided by number of days, then normalized to duration of 14 days. This would apply regardless of whether a patient actually received external assistance.
Time frame: Run-in period (14 days), treatment period 1 (14 days), and treatment period 2 (14 days)
Population: Participants with no major protocol deviations who were allocated to treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avexitide 45 mg Twice Daily | Rate of Level 3 Hypoglycemia | Run-in period | 2.5 events per 14 days | Standard Deviation 3.1 |
| Avexitide 45 mg Twice Daily | Rate of Level 3 Hypoglycemia | Treatment period | 0.8 events per 14 days | Standard Deviation 1.2 |
| Avexitide 90 mg Once Daily | Rate of Level 3 Hypoglycemia | Treatment period | 0.9 events per 14 days | Standard Deviation 2.9 |
| Avexitide 90 mg Once Daily | Rate of Level 3 Hypoglycemia | Run-in period | 2.5 events per 14 days | Standard Deviation 3.1 |
Comparison: Within-group analysisp-value: 0.0003Mixed effects model
Comparison: Within-group analysisp-value: 0.0003Mixed effects model