Conditions: Postbariatric Hypoglycemia
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 9
Healthy volunteers: no

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).

Arms:
arm 1: Subjects will receive two separate single doses (Period 1 and Period 2) of encapsulated mizagliflozin arm 2: Subjects will receive one dose of liquid formulation (Period 1), and one dose (optional) of encapsulated mizagliflozin (Period 2)

Interventions: intervention 1: Mizagliflozin
Intervention descriptions: intervention 1: Encapsulated or Liquid Formulation

Protocol document:
Prot_SAP_000.pdf: 
 
919.659.5677919.659.5677 
 
 
 
Phase 2 Randomized Single Ascending Dose Study in Post-Bariatric 
Hypoglycemia Subjects to Determine the Effect of Mizagliflozin 
Formulations on Postprandial Glucose and Insulin Levels 
 
Protocol : VGX-001-011 
 
 
NCT05541939 
 
May 1, 2024 
 
 


 
919.659.5677919.659.5677 
Protocol: 
Study Objective 
To evaluate the safety, tolerability, and pharmacodynamics of two formulations of mizagliflozin 
with respect to postprandial plasma glucose levels in participants with Post-Bariatric 
Hypoglycemia (PBH). 
Study Design 
This was a Phase 2 randomized, sequential crossover single ascending dose study in participants 
with PBH to determine the effect of two mizagliflozin formulations on safety, tolerability, and 
postprandial glucose and insulin levels. This study examined single doses of mizagliflozin (2.5, 
5.0, and 10.0 mg) in either a liquid (2.5 mg) or encapsulated (2.5, 5.0, and 10.0 mg) formulation. 
Participants were randomly assigned to one of two treatment arms (A: 2.5 mg 
encapsulated/washout/5 mg encapsulated, or B: 2.5 mg solution/washout/10 mg encapsulated). 
Baseline: A Baseline mixed meal tolerance test (MMTT) was performed once all screening 
assessments had been performed. Pharmacodynamic samples for glucose and insulin were 
obtained. 
Treatment Period: Following the Baseline MMTT assessment, subjects were randomized into 
Treatment Arm A or Treatment Arm B.  Subjects were administered the assigned dose/formulation 
followed by an MMTT. Pharmacodynamic samples for glucose and insulin were obtained. 
Participants 
Males and nonpregnant females, ages 18 to 75 years old, having had Roux-en-Y bariatric surgery 
more than 6 months prior to signing the ICF. 
History of reactive hypoglycemia with Whipple’s triad: the occurrence of hypoglycemic symptoms 
associated with blood glucose of ≤50 mg/dL, and resolution with glucose or carbohydrate 
administration. Symptoms associated with reactive hypoglycemia include neuroglycopenic 
symptoms (e.g., behavioral changes, confusion or impaired cognitive function, seizure, loss of 
consciousness). 
Inclusion Criteria: 
1. Males and nonpregnant females, ages 18 to 75 years old, having had Roux-en-Y bariatric 
surgery more than 6 months prior to signing the ICF. 
2. History of reactive hypoglycemia with Whipple’s triad: the occurrence of hypoglycemic 
symptoms associated with blood glucose of ≤50 mg/dL, and resolution with glucose or 
carbohydrate administration. Symptoms associated with reactive hypoglycemia include 
neuroglycopenic symptoms (e.g., behavioral changes, confusion or impaired cognitive 
function, seizure, loss of consciousness). 
3. Willing and able to give informed consent and follow all study procedures and 
requirements 
4. Subjects (male and female) must agree to use an adequate method of contraception from 
signed consent through 2 weeks after last dose of investigational product (IP).  


 
919.659.5677919.659.5677 
Adequate contraception is defined as a contraceptive method with a failure rate of 
less than 1% per year when used consistently and correctly and when applicable, in 
accordance with the product label, for example: abstinence from penile-vaginal 
intercourse; oral contraceptives, either combined or progestogen alone; injectable 
progestogen; implants of etonogestrel or levonorgestrel; estrogenic vaginal ring; 
percutaneous contraceptive patches; intrauterine device or intrauterine system; male 
partner sterilization at least 6 months prior to the female subject’s screening visit, and 
this male is the sole partner for that subject (the information on the male partner’s 
sterility can come from the site personnel’s review of the subject’s medical records or 
interview with the subject on her medical history); male condom combined with a 
vaginal spermicide (foam, gel, film, cream, or suppository); male condom combined 
with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, 
cream, or suppository). 
Exclusion Criteria: 
1. History of current medical conditions (other than PBH) which may result in 
hypoglycemia such as insulinoma, adrenal insufficiency, insulin autoimmune 
hypoglycemia, congenital hyperinsulinemia. 
2. Current use of insulin or insulin secretagogues. 
3. History of current dumping syndrome. 
4. History of current fasting hypoglycemia. 
5. Subjects in whom a structural disease of the large intestine (including occlusion, stenosis, 
cancer, and inflammatory bowel disease) was observed by colonoscopy or contrast enema 
performed within 3 years before consent or subjects suspected of having a structural 
disease of the large intestine 
6. Active infection or significant acute illness within 2 weeks prior to dosing 
7. Subjects with mental development disorder. 
8. Subjects who received the following drug therapies within 1 week before the start of the 
observation period (Week −2).  
a. Cathartics (bulk cathartic, osmotic laxative, stimulant laxative) 
b. Drugs that improve gastrointestinal function 
c. Herbal medicines indicated for constipation 
d. Drugs that inhibit intestinal motility 
e. Drugs for the treatment of irritable bowel syndrome  
f. Drugs for the treatment of chronic constipation 
g. Macrolides 
h. Supplements intended for improvement of constipation 
9. Subjects with a medical history of severe drug hypersensitivity 
10. Chronic kidney disease stage 4 or 5 


 
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11. Hepatic disease, including serum alanine aminotransferase or aspartate aminotransferase 
greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency 
as defined as serum albumin <3.0 g/dL; or serum total bilirubin >2.0 upper limit of 
normal at screening. 
12. Congestive heart failure, New York Heart Association class II, III or IV 
13. History of myocardial infarction, unstable angina or revascularization within the past 6 
months 
14. History of a cerebrovascular accident within 6 months of screening. 
15. Active treatment with any diabetes medications, except metformin. 
16. Active malignancy, except basal cell or squamous cell skin cancers 
17. Major surgical operation within 30 days prior to screening 
18. Blood donation (1 pint of whole blood) within the past 2 months 
19. Active alcohol abuse or substance abuse 
20. Current administration of oral or parenteral corticosteroids 
21. 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. 
22. Other subjects considered inappropriate by the Investigator  
Randomization and blinding 
After performing Baseline assessments and meeting randomization criteria, Subjects were 
randomized into one of two treatment arms in a 1:1 fashion.  The Treatment Arms are defined as 
follows:  
Treatment Arm 
 
A 
In Period 1, subjects will receive an encapsulated formulation of 2.5 mg 
mizagliflozin. Following at least a 7 day washout period, in Period 2, 
subjects will return to the clinic to receive an encapsulated formulation 
of 5.0 mg mizagliflozin. 
B 
In Period 1, subjects will receive a liquid dose formulation of 2.5 mg 
mizagliflozin.  If after consultation with the medical monitor and PI 
that there are no concerns regarding any treatment-related AEs, subjects 
will return to the clinic for a 10 mg encapsulated dose (Period 2) and 
MMTT after at least a 7 day washout period. 
 
As this is an open-label study, the subject, Investigator, site personnel and sponsor were not 
blinded to study drug.   


 
919.659.5677919.659.5677 
Procedures 
At in-clinic visits on visit days for MMTTs, patients reported to the clinic in the morning after a 
minimum 8 hour fast. A blood sample was obtained (Pre-MMTT). In addition, a clinical lab 
serum sample was collected. Shortly thereafter (within 30 min), subjects were administered a 
water dose (Baseline), or the assigned dose of mizagliflozin with water, and at 20 (±5) min, an 
MMTT was administered. The MMTT was started by consumption of a liquid meal (350 kcal 
distributed as 57% carbohydrate, 15% protein, and 28% fat). Pharmacodynamic blood samples to 
measure plasma glucose and insulin were collected at (hr:min) 0:05, 0:10, 0:20, 0:40, 1:00, 1:20, 
1:40, 2:00, 2:30, 3:00, 4:00, and 6:00 after MMTT initiation.  
Outcome Measurements 
Primary Endpoints 
• Safety endpoints were as follows: 
− Adverse Events 
− Vital signs (blood pressure, heart rate, respiratory rate, and body temperature) 
− Laboratory analyses (to include chemistries and hematology) 
− 12-lead ECGs 
• MMTT glucose nadir after mizagliflozin dosing [Time Frame: 0-3 hours]. 
Secondary Endpoints 
• MMTT plasma glucose and insulin peak concentration after mizagliflozin dosing 
[Time Frame: 0-3 hours]. 
• MMTT plasma glucose 1, 2, and 3 hour area under the curve (AUC0-1, AUC0-2, and 
AUC0-3) after mizagliflozin dosing  
• MMTT insulin concentration 1, 2, 3, 4, and 6 hour area under the curve (AUC0-1, 
AUC0-2, AUC0-3, AUC0-4, and AUC0-6) after mizagliflozin dosing  
• MMTT time to peak plasma glucose concentration after mizagliflozin dosing [Time 
Frame: 0-3 hours] 
• MMTT time to peak insulin concentration after mizagliflozin dosing [Time Frame: 
0-3 hours] 
Statistical Analysis Plan 
No formal hypothesis testing was planned. This study was sized for feasibility, study design optimization, 
and to investigate a difference in the nadir plasma glucose concentration during an MMTT. As such for 
descriptive purposes, in an inequality test on data from a three-period, single-sequence cross-over design, a 
sample size of 6 achieves approximately 80% power at a 2-sided 5.0% significance level when the absolute 
difference between the two treatment means is 15, the between-subject standard deviation is 14.6 and the 
correlation between any two measurements on the same subject is 0.6.