Effect of Mizagliflozin on Postprandial Glucose and Insulin in Post-Bariatric Hypoglycemia Subjects

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Postbariatric Hypoglycemia

Intervention / Treatment
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* Drug: Mizagliflozin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm A<br>Subjects will receive two separate single doses (Period 1 and Period 2) of encapsulated mizagliflozin | Drug: Mizagliflozin<br>* Encapsulated or Liquid Formulation<br>|
| Experimental: Treatment Arm B<br>Subjects will receive one dose of liquid formulation (Period 1), and one dose (optional) of encapsulated mizagliflozin (Period 2) | Drug: Mizagliflozin<br>* Encapsulated or Liquid Formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of participants with Adverse events | Through study completion, 34 days | 
| Vital Signs | Number of participants with abnormal vital signs | Through study completion, 34 days | 
| Laboratory Tests | Number of participants with abnormal laboratory tests | Through study completion, 34 days | 
| Electrocardiograms | Number of participants with abnormal electrocardiograms | Through study completion, 34 days | 
| Glucose nadir after mizagliflozin dosing | Time course of glucose concentrations during MMTT | 0-3 hours following liquid meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMTT time to peak plasma glucose concentration after mizagliflozin dosing | Time course of glucose concentrations during MMTT | 0-3 hours following liquid meal | 
| MMTT plasma glucose concentration | MMTT plasma glucose area under the curve (AUC0-1, AUC0-2, AUC0-3) after mizagliflozin dosing | 0-3 hours following liquid meal | 
| MMTT time to peak insulin concentration after mizagliflozin dosing | Time course of insulin concentrations during MMTT | 0-3 hours following liquid meal | 
| MMTT insulin concentration | MMTT insulin concentrations area under the curve (AUC0-1, AUC0-2, AUC0-3, AUC0-4, and AUC0-6) after mizagliflozin dosing | 0-6 hours following liquid meal | 
| Peak plasma glucose concentration after mizagliflozin dosing. | Time course of glucose concentrations during MMTT | 0-3 hours following liquid meal | 
| Peak insulin concentration after mizagliflozin dosing | Time course of insulin concentrations during MMTT | 0-3 hours following liquid meal |