Study to Determine the Safety, Tolerability, and Pharmacokinetic (PK) Profile of EGT0001474 in Healthy Volunteers

Study Overview
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Brief Summary
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This study evaluated the safety, tolerability and pharmacokinetics of single or multiple doses of EGT0001474.

Detailed Description
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EGT0001474 is an inhibitor of human sodium dependent glucose co-transporter II being developed for the treatment of Type II Diabetes mellitus. This is a singe center, Phase-1, double blinded,placebo controlled, dose escalation study of single and multiple ascending doses of EGT0001474 in healthy male and female subjects. In part-1, subjects were randomized to receive single doses of EGT0001474 at 2.5-150 mg or placebo in the ratio of 3:1. In part-2, subjects were randomized to receive 14 daily doses of EGT0001474 at 10, 50 and 150 mg or placebo in the ratio of 4:1. When the various doses were analysed, the maximum dose 150 mg was found to be tolerable. Although there was no serious adverse events, mild adverse events were observed. This study provided information on human safety, tolerability, PK and pharmacodynamic effects of EGT0001474.

Official Title
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A Phase I , Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of EGT0001474 In Healthy Volunteers

Conditions
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Safety and Tolerability of EGT0001474 in Healthy Volunteers

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 female volunteers between the ages of 18 and 55 years inclusive. In good health. Female subjects must be surgically sterilized or postmenopausal. Body mass index (BMI) between 18 kg/m2 and 30 kg/m2 inclusive. Non-smoker. Negative drug and alcohol screens. Exclusion Criteria: Abnormal ECG Sitting blood pressure above 140/90 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. History of drug abuse. Febrile illness within 5 days prior to the first dose of study medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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>Ascending doses of EGT0001474 | Drug: EGT0001474<br>* Oral ascending doses given daily as capsules for up to 14 days<br>* Other names: Human SGLT2 inhibitor;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo 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 |
| --- | --- | --- |
| Cmax | Pharmacokinetics results. Cmax -Maximum plasma drug concentration | Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days | 
| Tmax | Pharmacokinetics results. Time to maximum plasma drug concentration (Tmax) was calculated for each groups | Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days | 
| AUC 0-t | Pharmacokinetics results. AUC 0-t - Are under plasma concentration-time curve from time 0 time t. | Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days | 
| t1/2 | Pharmacokinetics results.t 1/2 - apparent terminal half life | Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days | 
| AUC 0 -24 | Pharmacokinetics results. Area under the plasma concentration-time curve from time 0 to 24 hours post-dose. | Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days | 
| Terminal Rate Constant. | Pharmacokinetics results. Terminal rate constant was estimated by linear regression of logarithmic transformed concentration versus time data | Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days | 
| CL/F | Pharmacokinetics results. Apparent oral clearance | Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days | 
| VZ/F | Pharmacokinetic results. Apparent volume of distribution | Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days | 

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