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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 2
• Intervention / Treatment: Drug: EGT0001442; Drug: Placebo capsules to match EGT0001442

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada
      • Research Site #03
    • London, Ontario, Canada
      • Research Site #13
    • Mississauga, Ontario, Canada
      • Research Site #02
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Research Site #10
  • California
    • National City, California, United States
      • Research Site #04
  • Colorado
    • Denver, Colorado, United States
      • Research Site #12
  • Florida
    • Miami, Florida, United States
      • Research Site #07
    • Miami, Florida, United States
      • Research Site #08
  • Pennsylvania
    • Reading, Pennsylvania, United States
      • Research Site #06
  • Texas
    • DeSoto, Texas, United States
      • Research Site #11
    • San Antonio, Texas, United States
      • Research Site #01
    • San Antonio, Texas, United States
      • Research Site #15

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo capsules to match EGT0001442; Segment 1: Not applicable. Segment 2: Diabetic subjects will be randomly assigned to receive oral placebo once daily for 28 days.; Other Names: Human SGLT2 inhibitor
Experimental: EGT0001442	Drug: EGT0001442; 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.; Other Names: Human SGLT2 inhibitor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Theracos
• Investigators: Study Chair: Mason W Freeman, M.D., Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2009
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: December 9, 2009
• First Submitted That Met QC Criteria: December 9, 2009
• First Posted (Estimate): December 10, 2009

Study Record Updates

• Last Update Posted (Actual): June 16, 2021
• Last Update Submitted That Met QC Criteria: June 15, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Diabetes Mellitus Type 2
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: THR-1442-C-402