Postbariatric Hypoglycemia
Conditions
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).
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.
Interventions
DRUGexendin 9-39
Exendin 9-39 is a competitive antagonist of GLP-1 at its receptor.
OTHERPlacebo
Placebo solution is identical to the active drug product except for the absence of the active ingredient, Exendin 9-39.
Sponsors
Eiger BioPharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postprandial Glucose Nadir | 3 hours following a liquid meal | Plasma glucose nadir occurring within 3 hours of mixed-meal tolerance testing (MMTT) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group 1 (Placebo, Exendin 9-39 30 mg BID, Exendin 9-39 60 mg QD) Placebo, exendin 9-39 30 mg BID, exendin 9-39 60 mg QD
exendin 9-39: Exendin 9-39 is a competitive antagonist of GLP-1 at its receptor.
Placebo: Placebo solution is identical to the active drug product except for the absence of the active ingredient, Exendin 9-39. | 8 |
| Treatment Group 2 (Placebo, Exendin 9-39 60 mg QD, Exendin 9-39 30 mg BID) Placebo, exendin 9-39 60 mg QD, exendin 9-39 30 mg BID
exendin 9-39: Exendin 9-39 is a competitive antagonist of GLP-1 at its receptor.
Placebo: Placebo solution is identical to the active drug product except for the absence of the active ingredient, Exendin 9-39. | 10 |
| Total | 18 |
Baseline characteristics
| Characteristic | Total | Treatment Group 1 (Placebo, Exendin 9-39 30 mg BID, Exendin 9-39 60 mg QD) | Treatment Group 2 (Placebo, Exendin 9-39 60 mg QD, Exendin 9-39 30 mg BID) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 8 Participants | 10 Participants |
| Body Mass Index | 29.6 kg/m^2 STANDARD_DEVIATION 4.1 | 30.0 kg/m^2 STANDARD_DEVIATION 3.1 | 29.3 kg/m^2 STANDARD_DEVIATION 4.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Female | 18 Participants | 8 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight | 81.23 kilograms STANDARD_DEVIATION 12.6 | 81.6 kilograms STANDARD_DEVIATION 7.3 | 81.0 kilograms STANDARD_DEVIATION 16.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 3 / 18 | 9 / 18 | 14 / 18 |
| serious Total, serious adverse events | 0 / 18 | 1 / 18 | 0 / 18 |
Outcome results
Primary
Postprandial Glucose Nadir
Plasma glucose nadir occurring within 3 hours of mixed-meal tolerance testing (MMTT)
Time frame: 3 hours following a liquid meal
Population: Analysis population are both treatment group 1 and treatment group 2. One participant was excluded from the efficacy analysis due to major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avexitide 30 mg BID | Postprandial Glucose Nadir | 57.1 mg/dL | Standard Deviation 16.5 |
| Avexitide 60 mg QD | Postprandial Glucose Nadir | 59.2 mg/dL | Standard Deviation 16.1 |
| Placebo | Postprandial Glucose Nadir | 47.1 mg/dL | Standard Deviation 12.7 |