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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00854113

Enrollment

Registered

2009-03-02

Start date

2009-02-28

Completion date

2009-07-31

Last updated

2019-06-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Safety and Tolerability of EGT0001474 in Healthy Volunteers

Keywords

Diabetes Mellitus Type 2

Brief summary

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

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.

Interventions

DRUGEGT0001474

Oral ascending doses given daily as capsules for up to 14 days

DRUGPlacebo

Placebo to match EGT0001474

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Cmax	Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days	Pharmacokinetics results. Cmax -Maximum plasma drug concentration
t1/2	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
Tmax	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
AUC 0-t	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.
AUC 0 -24	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.
Terminal Rate Constant.	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
CL/F	Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days	Pharmacokinetics results. Apparent oral clearance
VZ/F	Part-1 (Single dose) measured in 1 day and part 2 (multiple doses) measured in 14 days	Pharmacokinetic results. Apparent volume of distribution

Countries

United States

Participant flow

Participants by arm

Arm	Count
Part 1 - Single Dose EGT0001474 2.5 mg Treatment group - received 2.5 mg single dose of EGT0001474	6
Part 1 - Single Dose EGT0001474 5 mg Treatment group- received 5 mg single dose of EGT0001474	6
Part 1 -Single Dose EGT0001474 10 mg Treatment group- received 10 mg single dose of EGT0001474	6
Part 1 - Single Dose EGT0001474 25 mg Treatment group- received 25 mg single dose of EGT0001474	6
Part 1 - Single Dose EGT0001474 75 mg Treatment group- received 75 mg single dose of EGT0001474	6
Part 1 - Single Dose EGT0001474 150mg Treatment group- received 150 mg single dose of EGT0001474	6
Part 1 - Single Dose Placebo Placebo group- received single dose of placebo capsule	12
Part 2 - Mutiple Dose EGT0001474 10 mg Treatment group- received 14 daily doses of EGT0001474 at the dose of 10mg	8
Part 2 - Multiple Dose EGT0001474 50 mg Treatment group-received 14 daily doses of EGT0001474 at the dose of 50mg	8
Part 2 - Multiple Dose EGT0001474 150mg Treatment group-received 14 daily doses of EGT0001474 at the dose of 150mg	8
Part 2 - Multiple Dose Placebo Placebo group- received placebo capsules for 14 days	6
Total	78

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010
Overall Study	Adverse Event	0	0	0	0	0	0	0	2	0	0	0
Overall Study	Withdrawal by Subject	0	0	0	0	0	0	0	1	1	0	0

Baseline characteristics

Characteristic	Part 1 - Single Dose EGT0001474 2.5 mg	Total	Part 2 - Multiple Dose Placebo	Part 2 - Multiple Dose EGT0001474 150mg	Part 2 - Multiple Dose EGT0001474 50 mg	Part 2 - Mutiple Dose EGT0001474 10 mg	Part 1 - Single Dose Placebo	Part 1 - Single Dose EGT0001474 150mg	Part 1 - Single Dose EGT0001474 75 mg	Part 1 - Single Dose EGT0001474 25 mg	Part 1 -Single Dose EGT0001474 10 mg	Part 1 - Single Dose EGT0001474 5 mg
Age, Continuous	43 years	32 years	26 years	22 years	35 years	30 years	33 years	35 years	29 years	32 years	25 years	26 years
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	12 Participants	0 Participants	1 Participants	3 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants	66 Participants	6 Participants	7 Participants	5 Participants	7 Participants	11 Participants	6 Participants	6 Participants	5 Participants	5 Participants	4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Black or African American	6 Participants	64 Participants	5 Participants	6 Participants	5 Participants	7 Participants	11 Participants	6 Participants	4 Participants	6 Participants	3 Participants	5 Participants
Race/Ethnicity, Customized More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Others	0 Participants	7 Participants	0 Participants	2 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized White	0 Participants	7 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	1 Participants
Sex: Female, Male Female	1 Participants	30 Participants	6 Participants	8 Participants	6 Participants	8 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Sex: Female, Male Male	5 Participants	48 Participants	0 Participants	0 Participants	2 Participants	0 Participants	12 Participants	6 Participants	6 Participants	5 Participants	6 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	1 / 6	3 / 6	3 / 6	3 / 6	3 / 6	3 / 6	3 / 12	5 / 8	6 / 8	7 / 8	4 / 6
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 12	0 / 8	0 / 8	0 / 6	0 / 6

Outcome results

Primary

AUC 0 -24

Pharmacokinetics results. Area under the plasma concentration-time curve from time 0 to 24 hours post-dose.