Postbariatric Hypoglycemia
Conditions
Brief summary
This clinical study will examine the safety and tolerability, as well as the effects of orally administered mizagliflozin on post prandial glucose and insulin levels in subjects diagnosed with post-bariatric hypoglycemia (PBH).
Detailed description
This is a Phase 2 randomized, sequential crossover single ascending dose study in PBH subjects to determine the effect of two mizagliflozin formulations This study will examine single doses of mizagliflozin in either a liquid or encapsulated formulation. Subjects will be randomly assigned to one of two treatment arms. Safety, tolerability and pharmacodynamic response to mizagliflozin will be assessed in subjects during a mixed meal tolerance test (MMTT).
Interventions
DRUGMizagliflozin
Encapsulated or Liquid Formulation
Sponsors
Vogenx, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Roux-en-Y gastric bypass surgery performed \> 6 months prior to enrollment * Diagnosis of PBH
Exclusion criteria
* History of current medical conditions (other than PBH) which may result in hypoglycemia such as insulinoma, adrenal insufficiency, insulin autoimmune hypoglycemia, congenital hyperinsulinemia. * Current use of insulin or insulin secretagogues. * History of current dumping syndrome. * History of current fasting hypoglycemia. * Pregnancy and/ or Lactation: For women of childbearing potential: there is a requirement for a negative urine pregnancy test and for agreement to use contraception during the study and for at least 2 weeks after participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucose Nadir After Mizagliflozin Dosing | 0-3 hours following liquid meal | Time course of glucose concentrations during MMTT |
Countries
United States
Participant flow
Recruitment details
9 participants were screened between September 2022 and January 2023. 7 participants at University of Colorado/Anschutz Medical Campus and 2 participants at Stanford.University
Pre-assignment details
All 9 screened participants met eligibility criteria and were randomized
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm A Randomized participants received a Baseline MMTT. After approximately 7 days the participants returned to the clinic for Period 1 treatment, a single 2.5 mg capsule of mizagliflozin, followed by an MMTT. After a 7-day washout, participants returned to the clinic for Period 2 treatment, a single 5.0 mg capsule of mizagliflozin, followed by an MMTT.
Mizagliflozin: Encapsulated | 5 |
| Treatment Arm B Randomized participants received a Baseline MMTT. After approximately 7 days the participants returned to the clinic for Period 1 treatment, a single 2.5 mg liquid formulation of mizagliflozin, followed by an MMTT. After a 7-day washout, participants returned to the clinic for Period 2 treatment, a single 10.0 mg capsule of mizagliflozin, followed by an MMTT.
Mizagliflozin: Encapsulated or Liquid Formulation | 4 |
| Total | 9 |
Baseline characteristics
| Characteristic | Treatment Arm A | Treatment Arm B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 8 Participants |
| Baseline MMTT (pharmacodynamic assessment for glucose and insulin) | 5 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 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 | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 5 | 1 / 5 | 2 / 4 | 2 / 4 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Glucose Nadir After Mizagliflozin Dosing
Time course of glucose concentrations during MMTT
Time frame: 0-3 hours following liquid meal
Population: Change from Baseline MMTT in Glucose Nadir (mg/dL)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Glucose Nadir After Mizagliflozin Dosing | 2.5 mg Capsule | 6.2 mg/dL | Standard Deviation 14.8 |
| Treatment Arm A | Glucose Nadir After Mizagliflozin Dosing | 5.0 mg Capsule | 4.0 mg/dL | Standard Deviation 17.7 |
| Treatment Arm B | Glucose Nadir After Mizagliflozin Dosing | 2.5 mg Liquid | 17.5 mg/dL | Standard Deviation 30.5 |
| Treatment Arm B | Glucose Nadir After Mizagliflozin Dosing | 10.0 mg Capsule | 31.5 mg/dL | Standard Deviation 29 |