Safety, Tolerability and Pharmacokinetics Study of EGT0001474 in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability and pharmacokinetics (how much of the drug gets into the blood and how long it takes the body to get rid of it) of single doses of EGT0001474 given to patients with Type 2 diabetes. The study will also evaluate how EGT0001474 affects the amount of glucose produced by the body in the urine.

Detailed Description
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EGT0001474 is a compound that may inhibit the effect of other compounds in the body known as sugar transporters. The use of EGT0001474 may enhance the elimination of glucose from the blood by increasing the amount of urine produced. This would help prevent an abnormal decrease in blood sugar (hypoglycemia) both during fasting and after meals without increasing insulin secretion (which may result in weight gain or an abnormal increase in blood sugar known as Type 2 diabetes).

Official Title
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A Phase I, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of EGT0001474 in Subjects With Type 2 Diabetes

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: EGT0001474
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or females between the ages of 18 to 70 diagnosed with Type 2 diabetes. Body mass Index (BMI) between 18 kg/m2 and 37 kg/m2. HbA1c levels between 6.5 and 9.0 (inclusive) where the upper limit of normal for the HbA1c assay is 6.4% or 6.2-9.0% (inclusive) where the upper limit of normal for the HbA1c assay is 6.1% and fasting plasma glucose between 110 and 240 mg/dL (inclusive) while on diabetic medications. If taking drugs for diabetes, must be medically able and willing to discontinue diabetes medications for the duration of the study. Female subjects must be surgically sterilized or postmenopausal. Non-smoker for at least 3 months. Negative alcohol screen. Exclusion Criteria: Type 1 diabetes. Use of insulin therapy or oral antidiabetic medication other than metformin, sitagliptin or a sulfonylurea. Sitting blood pressure above 150/95 mmHg on 2 evaluations at least 10 minutes apart at screening. Treatment with an investigational drug within 30 days or 7 half-lives, whichever is longer. Previous treatment with EGT0001474. Vaccination within 30 days prior to the first dose of study medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EGT0001474<br> | Drug: EGT0001474<br>* Cohort 1: single dose of 25 mg EGT0001474 given as an oral capsule; Cohort 2: single dose of 75 mg EGT0001474 given as 3 oral capsules; Cohort 3: single dose of 150 mg EGT0001474 given as 6 oral capsules.<br>* Other names: Human SGLT2 inhibitor;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo capsules to match EGT0001474<br>* Other names: Human SGLT2 inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of EGT0001474 | Safety and tolerability were measured in terms of the number of mild, moderate and severe adverse events experienced by any participants. | 25 days | 
| AUC 0-t | Area under the plasma concentration-time curve from time 0 to time t | 3 days | 
| AUC0-24 | Area under the plasma concentration-time curve from time 0 to hour 24 | 3 days | 
| AUC Inf | Area under the plasma concentration-time curve from time 0 to infinity | 3 days | 
| Cmax | Maximum plasma concentration | 3 days | 
| Tmax | Time of maximum plasma concentration | 3 days | 
| λz | Terminal phase rate constant | 3 days | 
| t1/2 | Apparent terminal half life | 3 days | 
| CL/F | The apparent rate of oral clearance of EGT0001474.Oral clearance was defined as rate of drug removal from the body after oral administration. | 3 days | 
| Vz/F | Apparent volume of distribution | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus Type 2