Diabetes Mellitus
Conditions
Keywords
Diabetes mellitus
Brief summary
The purpose of the study is to evaluate the efficacy of EGT0001442 in lowering glycosylated Hemoglobin (HbA1c, A laboratory test to diagnose three months average of blood sugar)levels at 24th week from baseline, when compared to placebo group(no diabetic medication given). The secondary aim of the study is to evaluate the efficacy of EGT0001442 in lowering fasting blood glucose at the weeks 2 and 24 and comparing the results with placebo group. This study assess the efficacy of EGT0001442 based on the proportion of subjects who reach the American Diabetes Association (ADA) target of HbA1c of \< 7% in EGT0001442 group and comparison with placebo. The study also evaluates the effect of EGT0001442 on systolic, diastolic pressures, body weight and compare with the respective placebo groups.This study also assess the change from baseline in HbA1c overtime, from week 1 to week 96. Finally, to assess the safety of EGT0001442 in the Type 2 Diabetic patients (adult/maturity onset).
Detailed description
EGT0001442 is a compound that may inhibit the effect of other compounds in the body known as sugar transporters. The use of EGT0001442 may enhance the elimination of glucose from the blood by increasing the amount of urine produced. Hence the blood glucose levels are significantly decreased and the efficacy of EGT001442 can be established by assessing the three months average blood glucose levels (HbA1c). Due to the increased urinary output, the effect of EGT001442 on blood pressure levels are also assessed.
Interventions
DRUGEGT0001442
DRUGPlacebo
Sponsors
Theracos
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects ≥18 years old * Diagnosed with type 2 diabetes * Body mass index (BMI) ≤ 45 kg/m2 * HbA1c between 7 and 10% (inclusive) at screening * FPG \<250 mg/dL at screening for subjects not treated with oral anti-diabetic therapies or FPG \<240 mg/dL at screening for subjects treated with anti-diabetic therapies * Diabetes currently treated with diet and exercise only or diet and exercise along with one approved oral anti-diabetic agent * If taking anti-diabetic medication, dose and regimen must be stable for past 3 months * If taking anti-hypertensive medication, dose and regimen must be stable for past 3 months * If taking lipid modifying therapy, dose and regimen must be stable for past 3 months * Blood glucose \<250 mg/dL based on finger stick blood glucose for all subjects at randomization
Exclusion criteria
* Hemoglobinopathy that affects HbA1c measurement * Current use of injected therapy for treatment of diabetes (insulin or GLP-1 receptor based therapy) * Genitourinary tract infection within 6 weeks of screening * Greater than 2 episodes of genitourinary tract infection in the past year * History of kidney stones, bladder malfunction or other significant risk factor for urinary tract infections * eGFR, as calculated by the modification of diet in renal disease study equation (MDRD), \< 50 mL/min/1.73 m2 * Abnormal tests of liver function ALT, AST or bilirubin ≥ 3x ULN * Diagnosis of retinopathy or significant nephropathy (eGFR \< 50 mL/min/1.73 m2 * Uncontrolled hypertension (systolic blood pressure \>160 or diastolic blood pressure \>95) * Not willing to use effective birth control, if female with child-bearing potential * Life expectancy \< 2 years * New York Heart Association (NYHA) Class 4 heart failure * Sera positive of HCV, HIV, or positive on drug screen * Currently participating in another interventional trial * Previous treatment with EGT0001442 or EGT0001474 * Not able to comply with the study scheduled visits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c at 24 Weeks | Baseline and Week 24 | Changes from baseline in HbA1c in placebo and treatment group at end of 24 weeks treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Systolic and Diastolic Blood Pressure at Week 24 | Baseline and Week 24 | Changes from baseline in systolic and diastolic blood pressure in placebo and treatment group after 24 weeks of treatment |
| Changes in Body Weight at Week 24 | Baseline and week 24 | Changes from baseline in body weight in placebo and treatment group after 24 weeks of treatment |
| Change From Baseline in HbA1c Over 96 Weeks Time | Baseline and up to 96 weeks | Change from baseline in HbA1c level over 96 weeks in placebo and treatment group. The treatment group was treated with EGT0001442 for 24 weeks. |
| Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | 24 weeks | Changes from baseline in FPG in placebo and treatment group over 24 weeks of treatment |
| Percentage of Subjects Achieving HbA1c <7% | Baseline and up to 96 weeks | The number and percentage of subjects achieving HbA1c response levels \<7% for the FAS using LOCF is reported |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EGT0001442 EGT0001442 capsule, 20 mg, orally once daily | 145 |
| Placebo Placebo capsule, 20 mg, orally once daily | 141 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Physician Decision | 6 | 3 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Study terminated by Sponsor | 0 | 1 |
| Overall Study | Withdrawal by Subject | 25 | 28 |
Baseline characteristics
| Characteristic | Total | Placebo | EGT0001442 |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 10.64 | 54.7 years STANDARD_DEVIATION 10.3 | 56.2 years STANDARD_DEVIATION 10.94 |
| Baseline HbA1c Category < 8.5% | 187 Participants | 100 Participants | 87 Participants |
| Baseline HbA1c Category > 8.5% | 99 Participants | 41 Participants | 58 Participants |
| Body Mass Index | 30.1 kg/m2 STANDARD_DEVIATION 5.39 | 30.6 kg/m2 STANDARD_DEVIATION 5.41 | 29.7 kg/m2 STANDARD_DEVIATION 5.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 254 Participants | 125 Participants | 129 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 16 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 56 Participants | 25 Participants | 31 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 222 Participants | 112 Participants | 110 Participants |
| Sex: Female, Male Female | 169 Participants | 91 Participants | 78 Participants |
| Sex: Female, Male Male | 117 Participants | 50 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 145 | 0 / 141 |
| other Total, other adverse events | 50 / 145 | 62 / 141 |
| serious Total, serious adverse events | 3 / 145 | 12 / 141 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c at 24 Weeks
Changes from baseline in HbA1c in placebo and treatment group at end of 24 weeks treatment
Time frame: Baseline and Week 24
Population: Number of subjects with a value at baseline and at the specified visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| EGT0001442 | Change From Baseline in Hemoglobin A1c at 24 Weeks | -0.28 percentage of glycated hemoglobin | Standard Error 0.194 |
| Placebo | Change From Baseline in Hemoglobin A1c at 24 Weeks | 0.51 percentage of glycated hemoglobin | Standard Error 0.2 |
p-value: <0.000195% CI: [-1.06, -0.53]ANCOVA
Secondary
Change From Baseline in HbA1c Over 96 Weeks Time
Change from baseline in HbA1c level over 96 weeks in placebo and treatment group. The treatment group was treated with EGT0001442 for 24 weeks.
Time frame: Baseline and up to 96 weeks
Population: Number of subjects with a value at baseline and at the specified visit
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 18 | -0.28 percentage glycated hemoglobin | Standard Error 0.195 |
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 48 | -0.45 percentage glycated hemoglobin | Standard Error 0.215 |
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 12 | -0.19 percentage glycated hemoglobin | Standard Error 0.18 |
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 60 | -0.57 percentage glycated hemoglobin | Standard Error 0.219 |
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 24 | -0.28 percentage glycated hemoglobin | Standard Error 0.194 |
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 72 | -0.43 percentage glycated hemoglobin | Standard Error 0.213 |
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 6 | -0.11 percentage glycated hemoglobin | Standard Error 0.137 |
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 84 | -0.60 percentage glycated hemoglobin | Standard Error 0.218 |
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 36 | -0.52 percentage glycated hemoglobin | Standard Error 0.202 |
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 96 | -0.48 percentage glycated hemoglobin | Standard Error 0.215 |
| EGT0001442 | Change From Baseline in HbA1c Over 96 Weeks Time | Week 2 | -0.10 percentage glycated hemoglobin | Standard Error 0.083 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 96 | 0.54 percentage glycated hemoglobin | Standard Error 0.222 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 2 | 0.22 percentage glycated hemoglobin | Standard Error 0.084 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 6 | 0.49 percentage glycated hemoglobin | Standard Error 0.141 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 12 | 0.53 percentage glycated hemoglobin | Standard Error 0.186 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 18 | 0.43 percentage glycated hemoglobin | Standard Error 0.201 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 24 | 0.51 percentage glycated hemoglobin | Standard Error 0.2 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 36 | 0.42 percentage glycated hemoglobin | Standard Error 0.209 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 48 | 0.54 percentage glycated hemoglobin | Standard Error 0.222 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 60 | 0.41 percentage glycated hemoglobin | Standard Error 0.226 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 72 | 0.50 percentage glycated hemoglobin | Standard Error 0.22 |
| Placebo | Change From Baseline in HbA1c Over 96 Weeks Time | Week 84 | 0.38 percentage glycated hemoglobin | Standard Error 0.225 |
Comparison: Change from baseline in HbA1c (%) at Week 2p-value: <0.000195% CI: [-0.42, -0.21]ANCOVA
Comparison: Change from baseline in HbA1c (%) at Week 6p-value: <0.000195% CI: [-0.78, -0.41]ANCOVA
Comparison: Change from baseline in HbA1c (%) at Week 12p-value: <0.000195% CI: [-0.96, -0.48]ANCOVA
Comparison: Change from baseline in HbA1c (%) at Week 18p-value: <0.000195% CI: [-0.97, -0.44]ANCOVA
Comparison: Change from baseline in HbA1c (%) at Week 24p-value: <0.000195% CI: [-1.06, -0.53]ANCOVA
Comparison: Change from baseline in HbA1c (%) at Week 36p-value: <0.000195% CI: [-1.21, -0.66]ANCOVA
Comparison: Change from baseline in HbA1c (%) at Week 48p-value: <0.000195% CI: [-1.28, -0.7]ANCOVA
Comparison: Change from baseline in HbA1c (%) at Week 60p-value: <0.000195% CI: [-1.27, -0.68]ANCOVA
Comparison: Change from baseline in HbA1c (%) at Week 72p-value: <0.000195% CI: [-1.22, -0.64]ANCOVA
Comparison: Change from baseline in HbA1c (%) at Week 84p-value: <0.000195% CI: [-1.27, -0.69]ANCOVA
Comparison: Change from baseline in HbA1c (%) at Week 96p-value: <0.000195% CI: [-1.31, -0.73]ANCOVA
Secondary
Change From Baseline Over Time in Fasting Plasma Glucose (FPG)
Changes from baseline in FPG in placebo and treatment group over 24 weeks of treatment
Time frame: 24 weeks
Population: Only included number of subjects with a value at baseline and at the specified visit
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| EGT0001442 | Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | Week 6 | -1.23 mmol/L | Standard Error 0.482 |
| EGT0001442 | Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | Week 18 | -1.87 mmol/L | Standard Error 0.451 |
| EGT0001442 | Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | Week 12 | -1.75 mmol/L | Standard Error 0.489 |
| EGT0001442 | Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | Week 24 | -1.74 mmol/L | Standard Error 0.462 |
| EGT0001442 | Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | Week 2 | -1.39 mmol/L | Standard Error 0.407 |
| Placebo | Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | Week 24 | 0.89 mmol/L | Standard Error 0.478 |
| Placebo | Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | Week 2 | 0.85 mmol/L | Standard Error 0.422 |
| Placebo | Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | Week 6 | 1.22 mmol/L | Standard Error 0.499 |
| Placebo | Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | Week 12 | 0.67 mmol/L | Standard Error 0.507 |
| Placebo | Change From Baseline Over Time in Fasting Plasma Glucose (FPG) | Week 18 | 0.83 mmol/L | Standard Error 0.467 |
Comparison: Difference of mean-adjusted change from baseline in FPG (mmol/L) at Week 2, between EGT0001442 and Placebo group.p-value: <0.000195% CI: [-2.79, -1.7]ANCOVA
Comparison: Difference of mean-adjusted change from baseline in FPG (mmol/L) at Week 6, between EGT0001442 and Placebo group.p-value: <0.000195% CI: [-3.09, -1.81]ANCOVA
Comparison: Difference of mean-adjusted change from baseline in FPG (mmol/L) at Week 12, between EGT0001442 and Placebo group.p-value: <0.000195% CI: [-3.06, -1.77]ANCOVA
Comparison: Difference of mean-adjusted change from baseline in FPG (mmol/L) at Week 18, between EGT0001442 and Placebo group.p-value: <0.000195% CI: [-3.3, -2.11]ANCOVA
Comparison: Difference of mean-adjusted change from baseline in FPG (mmol/L) at Week 24, between EGT0001442 and Placebo group.p-value: <0.000195% CI: [-3.24, -2.02]ANCOVA
Secondary
Changes in Body Weight at Week 24
Changes from baseline in body weight in placebo and treatment group after 24 weeks of treatment
Time frame: Baseline and week 24
Population: Number of subjects with a value at baseline and at the specified visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| EGT0001442 | Changes in Body Weight at Week 24 | -2.95 kg | Standard Error 0.555 |
| Placebo | Changes in Body Weight at Week 24 | -1.22 kg | Standard Error 0.592 |
p-value: <0.000195% CI: [-2.52, -0.93]ANCOVA
Secondary
Changes in Systolic and Diastolic Blood Pressure at Week 24
Changes from baseline in systolic and diastolic blood pressure in placebo and treatment group after 24 weeks of treatment
Time frame: Baseline and Week 24
Population: Number of subjects with a value at baseline and a the specified visit
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| EGT0001442 | Changes in Systolic and Diastolic Blood Pressure at Week 24 | Systolic blood pressure | -8.62 mm Hg | Standard Error 1.903 |
| EGT0001442 | Changes in Systolic and Diastolic Blood Pressure at Week 24 | Diastolic blood pressure | -3.07 mm Hg | Standard Error 1.223 |
| Placebo | Changes in Systolic and Diastolic Blood Pressure at Week 24 | Systolic blood pressure | -3.08 mm Hg | Standard Error 1.964 |
| Placebo | Changes in Systolic and Diastolic Blood Pressure at Week 24 | Diastolic blood pressure | -0.40 mm Hg | Standard Error 1.275 |
p-value: <0.000195% CI: [-8.02, -3.04]ANCOVA
p-value: 0.001595% CI: [-4.3, -1.04]ANCOVA
Secondary
Percentage of Subjects Achieving HbA1c <7%
The number and percentage of subjects achieving HbA1c response levels \<7% for the FAS using LOCF is reported
Time frame: Baseline and up to 96 weeks
Population: Only included number of subjects with a value at baseline and at the specified visit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 6 | 22 Participants |
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 48 | 41 Participants |
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 18 | 29 Participants |
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 60 | 39 Participants |
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 2 | 14 Participants |
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 72 | 39 Participants |
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 12 | 27 Participants |
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 84 | 43 Participants |
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 36 | 35 Participants |
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 96 | 44 Participants |
| EGT0001442 | Percentage of Subjects Achieving HbA1c <7% | Week 24 | 33 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 96 | 14 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 2 | 13 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 6 | 15 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 12 | 17 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 18 | 14 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 24 | 14 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 36 | 14 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 48 | 20 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 60 | 18 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 72 | 17 Participants |
| Placebo | Percentage of Subjects Achieving HbA1c <7% | Week 84 | 16 Participants |