Safety and Efficacy Study of EGT0001442 in Subjects With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study was to assess the effect of EGT0001442 on fasting plasma glucose after 28 days of treatment in subjects with type 2 diabetes. The study also assessed the pharmacokinetics, safety and tolerability of EGT0001442, the effect on weight and HbA1c as well as the effect EGT0001442 has on the amount of glucose produced in the body by the urine.

Detailed Description
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This was a phase 2 study to evaluate the efficacy of EGT0001442. The study included two segments: Segment 1 was a single center, open labeled, ascending dose study in 4 groups of 5 diabetic subjects per group who received 5, 10, 20, or 50 mg of EGT0001442 capsules orally once daily for 28 days. The subjects were in clinic for the first 3 days for safety and PK evaluation. Segment 2 was a multi-center, double-blind, placebo-controlled parallel group study. One hundred and thirty one subjects in 5 parallel groups of approximately 25 diabetic subjects per group were randomly assigned to receive oral EGT0001442 at 5, 10, 20, or 50 mg/day or placebo once daily for 28 days in an outpatient setting.

Official Title
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A Phase II, Four-week, Multi-center, Double-blind, Placebo-controlled Parallel Group Study to Evaluate the Safety and Efficacy of EGT0001442 in Subjects With Type 2 Diabetes Mellitus With an Ascending Dose Safety and Pharmacokinetic Evaluation Period

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: EGT0001442
* Drug: Placebo capsules to match EGT0001442


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between the ages of 18 and 70 years diagnosed with type 2 diabetes. Body mass index (BMI) between 18 kg/m2 and 37 kg/m2 (inclusive). HbA1c levels between 6.5 and 9.5 (inclusive) where the upper limit of normal for the HbA1c assay is 6.4% or HbA1c levels between 6.2 and 9.5% (inclusive) where the upper limit of normal for the HbA1c assay is 6.1%. Fasting plasma glucose levels between 126 and 270 mg/dL (7 - 15 mmol/L, inclusive) while on diabetic medications. Treatment naïve subjects with HbA1c between 6.5 and 9.5 and fasting plasma glucose between 126 and 270 mg/dL (7 - 15 mmol/L). If taking drugs for diabetes, must be medically able and willing to discontinue diabetic medications for the duration of the study. Female subjects must be surgically sterilized or postmenopausal. Exclusion Criteria: Type 1 diabetes or diabetes treated with insulin injection. Insulin therapy or oral antidiabetic medication other than metformin, sitagliptin, saxagliptin, a sulfonylurea or combination of these. Sitting blood pressure above 150/95 mmHg on two evaluations at least 10 minutes apart at screening. Positive results on screen for drugs of abuse. Previous treatment with an investigational drug within 30 days or 7 half-lives, whichever is longer. Previous treatment with EGT0001474 or EGT0001442.

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: EGT0001442<br> | Drug: EGT0001442<br>* Segment 1 is a single center, open labeled, ascending dose study in diabetic subjects who will receive 5, 10, 20, or 50 mg of EGT0001442 capsules orally once daily for 28 days. Segment 2 is a multi-center, double-blind, placebo-controlled parallel group study. Diabetic subjects will be randomly assigned to receive oral EGT0001442 at 5, 10, 20, or 50 mg/day for 28 days.<br>* Other names: Human SGLT2 inhibitor;|
| Placebo Comparator: Placebo<br> | Drug: Placebo capsules to match EGT0001442<br>* Segment 1: Not applicable. Segment 2: Diabetic subjects will be randomly assigned to receive oral placebo once daily for 28 days.<br>* Other names: Human SGLT2 inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Fasting Plasma Glucose (FPG) From Baseline at Week 4 for Segment 2 of the Study | Fasting glucose levels were measured at four time points; At day -2, day 1, day 27 and day 29 (24-h after the last dose). Baseline is defined as the mean of FPG values on day -2 and day 1. End of treatment is defined as the mean of FPG values on day 27 and day 29. Changes in the FPG during the study period was calculated by subtracting the Baseline FPG from End of Treatment FPG. | Baseline; Day -2 and Day 1. End of Treatment: Day 27 and Day 29 | 
| Pharmacokinetics of EGT0001442 (Cmax) at 4 Dose Levels at Week 4 | Blood samples were collected during Segment 1 at pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12 and 24 h (day 2), and 48 h (day 3) post dose for the determination of EGT0001442. Plasma concentrations of EGT0001442 were measured using a validated HPLC/MS-MS method and PK parameters were calculated by standard noncompartmental methods. | Pre-dose to 48 h post-dose | 
| Pharmacokinetics of EGT0001442 (AUC 0-t and 0-24) at 4 Dose Levels at Week 4 | Blood samples were collected during Segment 1 at pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 12 and 24 h (day 2), and 48 h (day 3) post dose for the determination of EGT0001442. Plasma concentrations of EGT0001442 were measured using a validated HPLC/MS-MS method and PK parameters were calculated by standard noncompartmental methods. | Pre-dose to 48 h post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Body Weight From Baseline at Week 4 | Changes in the body weight during the study period was calculated by subtracting body weight on day 1 from body weight at the end of treatment on day 29. | Baseline and Day 29 | 
| Changes in Hemoglobin A1c (HbA1c) From Baseline at Week 4 | HbA1c levels were measured at two time points; on day 1 and day 29 (end of treatment). Changes in the HbA1c level during the study period was calculated by subtracting HbA1c level on day 1 from HbA1c level at the end of treatment (day 29) | Baseline and Day 29 | 
| Change in Urinary Glucose Excretion From Baseline to Day 1 and Day 28 | Urinary glucose levels were measured at three time points; on Day 0 (baseline), Day 1 and Day 28 (end of treatment). Changes in the urinary glucose level during the study period was calculated by reducing the baseline urinary glucose level (Day 1) from urinary glucose level at end of treatment (Day 28) (i.e urinary glucose level on Day 28 minus urinary glucose level on Day 1). | Baseline, Day 1 and Day 28 | 
| Change in FPG Following Cessation of Treatment | The mean change in FPG following cessation of treatment was obtained by calculating the difference between FPG values obtained on End of treatment (average of FPG values on days 27 and 29) and on Post Treatment (average of FPG values on days 41 and 43). | Days 27/29 to Days 41/43 | 

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