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

• ClinicalTrials.gov Identifier: NCT00854113
• Recruitment Status: Completed
• First Posted: March 2, 2009
• Results First Posted: August 12, 2011
• Last Update Posted: June 6, 2019
• Sponsor: Theracos
• Information provided by: Theracos

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Safety and Tolerability of EGT0001474 in Healthy Volunteers	Drug: EGT0001474; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase I , Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of EGT0001474 In Healthy Volunteers
• Study Start Date: February 2009
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: EGT0001474; Ascending doses of EGT0001474	Drug: EGT0001474; Oral ascending doses given daily as capsules for up to 14 days; Other Name: Human SGLT2 inhibitor
Placebo Comparator: Placebo; Placebo	Drug: Placebo; Placebo to match EGT0001474; Other Name: Human SGLT2 inhibitor

Outcome Measures

Primary Outcome Measures :

1. Cmax [ Time Frame: Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days ]
   Pharmacokinetics results. Cmax -Maximum plasma drug concentration
2. Tmax [ Time Frame: Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days ]
   Pharmacokinetics results. Time to maximum plasma drug concentration (Tmax) was calculated for each groups
3. AUC 0-t [ Time Frame: Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days ]
   Pharmacokinetics results. AUC 0-t - Are under plasma concentration-time curve from time 0 time t.
4. t1/2 [ Time Frame: Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days ]
   Pharmacokinetics results.t 1/2 - apparent terminal half life
5. AUC 0 -24 [ Time Frame: Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days ]
   Pharmacokinetics results. Area under the plasma concentration-time curve from time 0 to 24 hours post-dose.
6. Terminal Rate Constant. [ Time Frame: Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days ]
   Pharmacokinetics results. Terminal rate constant was estimated by linear regression of logarithmic transformed concentration versus time data
7. CL/F [ Time Frame: Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days ]
   Pharmacokinetics results. Apparent oral clearance
8. VZ/F [ Time Frame: Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days ]
   Pharmacokinetic results. Apparent volume of distribution

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Wisconsin

Covance Clinical Research Unit

Madison, Wisconsin, United States, 53704

Sponsors and Collaborators

Theracos

Investigators

• Study Chair: Mason W. Freeman, M.D.; Massachusetts General Hospital

More Information

• Responsible Party: Albert Collinson Ph.D, President and CEO, Theracos
• ClinicalTrials.gov Identifier: NCT00854113
• Other Study ID Numbers: THR-1474-C-328
• First Posted: March 2, 2009
• Results First Posted: August 12, 2011
• Last Update Posted: June 6, 2019
• Last Verified: June 2019

Keywords provided by Theracos:

Diabetes Mellitus Type 2

Additional relevant MeSH terms:

Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Physiological Effects of Drugs