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

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

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

Study Overview

• Status: Completed
• Conditions: Safety and Tolerability of EGT0001474 in Healthy Volunteers
• Intervention / Treatment: Drug: EGT0001474; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo to match EGT0001474; Other Names: Human SGLT2 inhibitor
EXPERIMENTAL: EGT0001474; Ascending doses of EGT0001474	Drug: EGT0001474; Oral ascending doses given daily as capsules for up to 14 days; Other Names: Human SGLT2 inhibitor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Theracos

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (ACTUAL): July 1, 2009
• Study Completion (ACTUAL): July 1, 2009

Study Registration Dates

• First Submitted: February 27, 2009
• First Submitted That Met QC Criteria: February 27, 2009
• First Posted (ESTIMATE): March 2, 2009

Study Record Updates

• Last Update Posted (ACTUAL): June 6, 2019
• Last Update Submitted That Met QC Criteria: June 4, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Diabetes Mellitus Type 2
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: THR-1474-C-328