Effect of Mizagliflozin Repeat Dosing on Adverse Events and Postprandial Glucose Excursions

Study Overview
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Brief Summary
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This is a phase 2 crossover, randomized, placebo-controlled, single-blind, repeat dose study in PBH subjects to determine the effect of mizagliflozin on adverse events and postprandial glucose excursions.

Detailed Description
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This is a phase 2 crossover, randomized, placebo-controlled, single-blind, repeat dose study in PBH subjects to determine the effect of mizagliflozin on adverse events and postprandial glucose excursions. This study will examine repeat doses of mizagliflozin and placebo while also evaluating dosing regimen. Up to 15 subjects are expected to complete the study. Subjects will be randomly assigned to a treatment arm within a cohort. Each subject should receive placebo and 2 active dose regimens in a crossover fashion.

Official Title
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Phase 2 Crossover, Randomized, Placebo-Controlled, Single-Blind, Repeat Dose Study in Post-Bariatric Hypoglycemia Subjects to Determine the Effect of Mizagliflozin on Adverse Events and Postprandial Glucose Excursions

Conditions
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Postbariatric Hypoglycemia

Intervention / Treatment
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* Drug: Mizagliflozin
* Drug: Placebo


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 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Subjects will receive placebo and two doses of encapsulated mizagliflozin over three dosing periods. Once and twice daily dosing will be examined. | Drug: Mizagliflozin<br>* Encapsulated<br>Drug: Placebo<br>* Encapsulated<br>|
| Experimental: Cohort 2<br>Subjects will receive placebo and two doses of encapsulated mizagliflozin over three dosing periods. Twice and three times daily dosing will be examined. | Drug: Mizagliflozin<br>* Encapsulated<br>Drug: Placebo<br>* Encapsulated<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, 43 days | 
| Vital Signs | Number of participants with abnormal vital signs | Through study completion, 43 days | 
| Laboratory Tests | Number of participants with abnormal laboratory tests | Through study completion, 43 days | 
| Glucose nadir after dosing | Time course of glucose concentrations during MMTT | 0-3 hours following liquid meal | 

Secondary Outcome Measures

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