Diabetic Kidney Disease
Conditions
Keywords
Diabetic Kidney Disease, XO inhibitor, UACR
Brief summary
The primary objective of this study is to assess the effect of 2 dose levels of TMX-049 on urinary albumin excretion in subjects with Type 2 diabetes and albuminuria (a urinary albumin-to-creatinine ratio (UACR) 200 to 3000 mg/g and an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m2). Effects of each TMX-049 dose on UACR will be assessed in terms of ratios using log-transformed UACR at Baseline and after a 12-week period of treatment.
Interventions
DRUGTMX-049
A certain dose of TMX-049 to be taken orally, once daily
DRUGPlacebo
Matching placebo to be taken orally, once daily
Sponsors
Teijin America, Inc.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes treated with ≥1 glucose-lowering medication for at least 12 months * UACR 200 to 3000 mg/g * eGFR ≥30 ml/min/1.73m2 * Treated with at least the minimal recommended dose of an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB), but not both
Exclusion criteria
* History of Type 1 diabetes * Women who are breast feeding * Treatment with any uric acid-lowering therapy within previous 2 weeks * History of intolerance to any XO (xanthine oxidase) inhibitor * History of a gout flare requiring pharmacologic treatment * History or presence of tophaceous gout * History of immunosuppressant treatment for any known or suspected renal disorder * History of a non-diabetic form of renal disease * Glycosylated hemoglobin (HbA1c) \>11% * sUA \<4.0 mg/dL or \>10.0 mg/dL * Positive urinary pregnancy test * Dialysis for acute renal failure within previous 6 months * Renal allograft in place or a scheduled kidney transplant within the next 22 weeks * Congenital or acquired solitary kidney
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at Week 12 | Baseline and Week 12 | UACR from Baseline to Weeks 2, 6, 12, and 16(Follow-up) were measured. The change from baseline at Week 12 in log-transformed UACR was analyzed and reported as a primary outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Serum Uric Acid (sUA) | Baseline and Week 2, 6, 12, 16 (Follow-up) | Serum Uric Acid from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured in order to explore the sUA (Serum Uric Acid) lowering effect in DKD (diabetic kidney disease) patients and the relationship between sUA and efficacy to DKD. |
| Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Baseline and Week 2, 6, 12, 16 (Follow-up) | Urinary Albumin-to-Creatinine Ratio from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. |
| Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio | 16 Weeks | Changes in Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio were measured. Subject with greater than 30% reduction is estimated as responder, less than or equal to 30% reduction is estimated as non-responder. |
| Changes in Exploratory Blood Biomarkers (C Reactive Protein) | 16 Weeks | Changes in Exploratory Blood Biomarkers for inflammation (C Reactive Protein) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. |
| Changes in Estimated Glomerular Filtration Rate (GFR) | Baseline and Week 2, 6, 12, 16 (Follow-up) | Estimated Glomerular Filtration Rate from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. The eGFR (estimated glomerular filtration rate) was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula based on the serum creatinine measurement. |
| Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | 16 Weeks | Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Fatty Acid Binding Protein 1) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. |
| Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | 16 Weeks | Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Hydroxy Deoxyguanosine) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. |
| Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | 16 Weeks | Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Kidney Injury Molecule-1) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. |
| Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | 16 Weeks | Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. |
| Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | 16 Weeks | Changes in Exploratory Blood Biomarkers for inflammation (Soluble TNF \[tumor necrosis factor\] Receptor Type I) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TMX-049 Placebo Placebo: Matching placebo to be taken orally, once daily | 42 |
| TMX-049 40 mg QD TMX-049: 40 mg of TMX-049 to be taken orally, once daily | 43 |
| TMX-049 200 mg QD TMX-049: 200 mg of TMX-049 to be taken orally, once daily | 44 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Protocol Deviation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | TMX-049 Placebo | TMX-049 40 mg QD | TMX-049 200 mg QD | Total |
|---|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 10.3 | 66 years STANDARD_DEVIATION 10.7 | 68 years STANDARD_DEVIATION 10 | 66 years STANDARD_DEVIATION 10.3 |
| BMI | 31.6 kg/m^2 STANDARD_DEVIATION 6 | 33.6 kg/m^2 STANDARD_DEVIATION 6.57 | 34.3 kg/m^2 STANDARD_DEVIATION 7.26 | 32.2 kg/m^2 STANDARD_DEVIATION 6.69 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 2 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 8 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 38 Participants | 35 Participants | 105 Participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 18 Participants | 53 Participants |
| Sex: Female, Male Male | 24 Participants | 26 Participants | 26 Participants | 76 Participants |
| Weight | 90.1 kg STANDARD_DEVIATION 19.81 | 95.9 kg STANDARD_DEVIATION 20.58 | 98.8 kg STANDARD_DEVIATION 23.63 | 95.0 kg STANDARD_DEVIATION 21.57 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 44 | 0 / 44 |
| other Total, other adverse events | 18 / 42 | 19 / 44 | 17 / 44 |
| serious Total, serious adverse events | 4 / 42 | 4 / 44 | 2 / 44 |
Outcome results
Primary
Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at Week 12
UACR from Baseline to Weeks 2, 6, 12, and 16(Follow-up) were measured. The change from baseline at Week 12 in log-transformed UACR was analyzed and reported as a primary outcome.
Time frame: Baseline and Week 12
Population: Modified Intention-to-Treat (mITT) Population consisted of all randomized subjects who had at least 1 post-randomization UACR assessment. Subjects in the mITT Population were analyzed according to their randomized treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TMX-049 Placebo | Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at Week 12 | -0.10 Log(mg/g) | Standard Error 0.153 |
| TMX-049 40 mg QD | Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at Week 12 | -0.15 Log(mg/g) | Standard Error 0.151 |
| TMX-049 200 mg QD | Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at Week 12 | -0.53 Log(mg/g) | Standard Error 0.15 |
Comparison: Change from baseline in log-transformed UACR was analyzed using an ANCOVA model with randomized treatment, and randomization strata of sUA and UACR as independent variables. The last observation carried forward imputation was used for missing data. In this study, multiplicity was not considered since the study objective is exploratory.p-value: 0.795395% CI: [-0.44, 0.34]ANCOVA
Comparison: Change from baseline in log-transformed UACR was analyzed using an ANCOVA model with randomized treatment, and randomization strata of sUA and UACR as independent variables. The last observation carried forward imputation was used for missing data. In this study, multiplicity was not considered since the study objective is exploratory.p-value: 0.031195% CI: [-0.82, -0.04]ANCOVA
Secondary
Changes in Estimated Glomerular Filtration Rate (GFR)
Estimated Glomerular Filtration Rate from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured. The eGFR (estimated glomerular filtration rate) was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula based on the serum creatinine measurement.
Time frame: Baseline and Week 2, 6, 12, 16 (Follow-up)
Population: Modified Intention-to-Treat (mITT) Population consisted of all randomized subjects who had at least 1 post-randomization UACR assessment. Subjects in the mITT Population were analyzed according to their randomized treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| TMX-049 Placebo | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 4 (Week 2) | -0.02 ml/min/1.73 m^2 | Standard Error 1.591 |
| TMX-049 Placebo | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 5 (Week 6) | -1.41 ml/min/1.73 m^2 | Standard Error 1.757 |
| TMX-049 Placebo | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 6/ET (Week 12) | -2.34 ml/min/1.73 m^2 | Standard Error 1.585 |
| TMX-049 Placebo | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 7/Follow up (Week 16) | -2.39 ml/min/1.73 m^2 | Standard Error 1.726 |
| TMX-049 40 mg QD | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 7/Follow up (Week 16) | 1.57 ml/min/1.73 m^2 | Standard Error 1.702 |
| TMX-049 40 mg QD | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 4 (Week 2) | 0.98 ml/min/1.73 m^2 | Standard Error 1.601 |
| TMX-049 40 mg QD | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 6/ET (Week 12) | -0.62 ml/min/1.73 m^2 | Standard Error 1.563 |
| TMX-049 40 mg QD | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 5 (Week 6) | -1.06 ml/min/1.73 m^2 | Standard Error 1.732 |
| TMX-049 200 mg QD | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 7/Follow up (Week 16) | 0.99 ml/min/1.73 m^2 | Standard Error 1.695 |
| TMX-049 200 mg QD | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 5 (Week 6) | 0.00 ml/min/1.73 m^2 | Standard Error 1.724 |
| TMX-049 200 mg QD | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 6/ET (Week 12) | 1.09 ml/min/1.73 m^2 | Standard Error 1.556 |
| TMX-049 200 mg QD | Changes in Estimated Glomerular Filtration Rate (GFR) | Visit 4 (Week 2) | 0.18 ml/min/1.73 m^2 | Standard Error 1.561 |
Comparison: For Week 12 (visit of the primary outcome), ANCOVA model with treatment, randomization strata of sUA and UACR levels as independent variables, Baseline eGFR as covariate is fitted. The last observation carried forward imputation was used for missing data.p-value: 0.405595% CI: [-2.35, 5.78]ANCOVA
Comparison: For Week 12 (visit of the primary outcome), an ANCOVA model with treatment, randomization strata of sUA and UACR levels as independent variables, Baseline eGFR as covariate is fitted. The last observation carried forward imputation was used for missing data.p-value: 0.09695% CI: [-0.62, 7.46]ANCOVA
Secondary
Changes in Exploratory Blood Biomarkers (C Reactive Protein)
Changes in Exploratory Blood Biomarkers for inflammation (C Reactive Protein) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time frame: 16 Weeks
Population: Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMX-049 Placebo | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 6/ET (Week 12) | 0.000 mg/dL | Standard Deviation 0.7527 |
| TMX-049 Placebo | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 7/ Follow up (Week 16) | 0.012 mg/dL | Standard Deviation 0.6507 |
| TMX-049 Placebo | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 5 (Week 6) | -0.011 mg/dL | Standard Deviation 0.6443 |
| TMX-049 Placebo | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 4 (Week 2) | 0.046 mg/dL | Standard Deviation 0.5168 |
| TMX-049 40 mg QD | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 4 (Week 2) | 0.014 mg/dL | Standard Deviation 0.5384 |
| TMX-049 40 mg QD | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 5 (Week 6) | 0.003 mg/dL | Standard Deviation 0.3688 |
| TMX-049 40 mg QD | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 7/ Follow up (Week 16) | -0.084 mg/dL | Standard Deviation 0.3606 |
| TMX-049 40 mg QD | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 6/ET (Week 12) | -0.144 mg/dL | Standard Deviation 0.3691 |
| TMX-049 200 mg QD | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 7/ Follow up (Week 16) | -0.046 mg/dL | Standard Deviation 0.3917 |
| TMX-049 200 mg QD | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 4 (Week 2) | 0.087 mg/dL | Standard Deviation 0.6194 |
| TMX-049 200 mg QD | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 5 (Week 6) | -0.084 mg/dL | Standard Deviation 0.4303 |
| TMX-049 200 mg QD | Changes in Exploratory Blood Biomarkers (C Reactive Protein) | Visit 6/ET (Week 12) | 0.000 mg/dL | Standard Deviation 0.5176 |
Secondary
Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I)
Changes in Exploratory Blood Biomarkers for inflammation (Soluble TNF \[tumor necrosis factor\] Receptor Type I) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time frame: 16 Weeks
Population: Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMX-049 Placebo | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 4 (Week 2) | -13.7 ng/L | Standard Deviation 367.11 |
| TMX-049 Placebo | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 5 (Week 6) | -77.1 ng/L | Standard Deviation 295.5 |
| TMX-049 Placebo | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 6 (Week 12) | 16.5 ng/L | Standard Deviation 371.88 |
| TMX-049 Placebo | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 7/Follow up (Week 16) | -25.8 ng/L | Standard Deviation 366.94 |
| TMX-049 40 mg QD | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 7/Follow up (Week 16) | -36.3 ng/L | Standard Deviation 308.79 |
| TMX-049 40 mg QD | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 4 (Week 2) | -92.3 ng/L | Standard Deviation 298.83 |
| TMX-049 40 mg QD | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 6 (Week 12) | 10.8 ng/L | Standard Deviation 455.11 |
| TMX-049 40 mg QD | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 5 (Week 6) | 47.6 ng/L | Standard Deviation 485.92 |
| TMX-049 200 mg QD | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 7/Follow up (Week 16) | 13.8 ng/L | Standard Deviation 320.22 |
| TMX-049 200 mg QD | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 5 (Week 6) | 60.7 ng/L | Standard Deviation 397.76 |
| TMX-049 200 mg QD | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 6 (Week 12) | 43.8 ng/L | Standard Deviation 265.35 |
| TMX-049 200 mg QD | Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I) | Visit 4 (Week 2) | 38.7 ng/L | Standard Deviation 360.03 |
Secondary
Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1)
Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Fatty Acid Binding Protein 1) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time frame: 16 Weeks
Population: Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 4 (Week 2) | 0.03 ug/L/mg/dL | Standard Deviation 0.161 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 5 (Week 6) | -0.04 ug/L/mg/dL | Standard Deviation 0.309 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 6 (Week 12) | -0.01 ug/L/mg/dL | Standard Deviation 0.317 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 7/Follow up (Week 16) | 0.02 ug/L/mg/dL | Standard Deviation 0.321 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 7/Follow up (Week 16) | 0.04 ug/L/mg/dL | Standard Deviation 0.289 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 4 (Week 2) | 0.01 ug/L/mg/dL | Standard Deviation 0.214 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 6 (Week 12) | -0.01 ug/L/mg/dL | Standard Deviation 0.136 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 5 (Week 6) | 0.04 ug/L/mg/dL | Standard Deviation 0.258 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 7/Follow up (Week 16) | 0.00 ug/L/mg/dL | Standard Deviation 0.188 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 5 (Week 6) | -0.04 ug/L/mg/dL | Standard Deviation 0.201 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 6 (Week 12) | -0.01 ug/L/mg/dL | Standard Deviation 0.218 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1) | Visit 4 (Week 2) | -0.04 ug/L/mg/dL | Standard Deviation 0.201 |
Secondary
Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine)
Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Hydroxy Deoxyguanosine) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time frame: 16 Weeks
Population: Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 4 (Week 2) | 1.47 nmol/L/mg/dL | Standard Deviation 4.266 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 5 (Week 6) | 1.72 nmol/L/mg/dL | Standard Deviation 5.179 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 6 (Week 12) | -1.86 nmol/L/mg/dL | Standard Deviation 5.372 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 7/ Follow up (Week 16) | 1.20 nmol/L/mg/dL | Standard Deviation 5.48 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 7/ Follow up (Week 16) | -0.07 nmol/L/mg/dL | Standard Deviation 5.647 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 4 (Week 2) | 4.70 nmol/L/mg/dL | Standard Deviation 4.123 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 6 (Week 12) | 3.75 nmol/L/mg/dL | Standard Deviation 6.157 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 5 (Week 6) | 3.22 nmol/L/mg/dL | Standard Deviation 5.321 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 7/ Follow up (Week 16) | -3.14 nmol/L/mg/dL | Standard Deviation 5.211 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 5 (Week 6) | 4.88 nmol/L/mg/dL | Standard Deviation 5.93 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 6 (Week 12) | 6.87 nmol/L/mg/dL | Standard Deviation 10.476 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine) | Visit 4 (Week 2) | 6.08 nmol/L/mg/dL | Standard Deviation 5.809 |
Secondary
Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1)
Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected Kidney Injury Molecule-1) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time frame: 16 Weeks
Population: Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 4 (Week 2) | 0.00 ug/L/mg/dL | Standard Deviation 0.01 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 5 (Week 6) | 0.00 ug/L/mg/dL | Standard Deviation 0.01 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 6 (Week 12) | 0.00 ug/L/mg/dL | Standard Deviation 0.019 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 7/Follow up (Week 16) | 0.00 ug/L/mg/dL | Standard Deviation 0.009 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 7/Follow up (Week 16) | 0.00 ug/L/mg/dL | Standard Deviation 0.0014 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 4 (Week 2) | 0.00 ug/L/mg/dL | Standard Deviation 0.016 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 6 (Week 12) | 0.00 ug/L/mg/dL | Standard Deviation 0.015 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 5 (Week 6) | 0.00 ug/L/mg/dL | Standard Deviation 0.015 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 7/Follow up (Week 16) | 0.00 ug/L/mg/dL | Standard Deviation 0.009 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 5 (Week 6) | 0.00 ug/L/mg/dL | Standard Deviation 0.006 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 6 (Week 12) | 0.00 ug/L/mg/dL | Standard Deviation 0.008 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1) | Visit 4 (Week 2) | 0.00 ug/L/mg/dL | Standard Deviation 0.007 |
Secondary
Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase)
Changes in Exploratory Renal Biomarkers for renal tubular diseases (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time frame: 16 Weeks
Population: Safety Population consisted of all randomized subjects who received at least one study drug tablet or capsule. Subjects were analyzed according to the actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 4 (Week 2) | -0.01 U/L/mg/dL | Standard Deviation 0.129 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 5 (Week 6) | 0.02 U/L/mg/dL | Standard Deviation 0.154 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 6 (Week 12) | 0.00 U/L/mg/dL | Standard Deviation 0.123 |
| TMX-049 Placebo | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 7/Follow up (Week 16) | 0.01 U/L/mg/dL | Standard Deviation 0.089 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 7/Follow up (Week 16) | 0.02 U/L/mg/dL | Standard Deviation 0.116 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 4 (Week 2) | 0.03 U/L/mg/dL | Standard Deviation 0.136 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 6 (Week 12) | 0.02 U/L/mg/dL | Standard Deviation 0.143 |
| TMX-049 40 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 5 (Week 6) | 0.02 U/L/mg/dL | Standard Deviation 0.121 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 7/Follow up (Week 16) | -0.01 U/L/mg/dL | Standard Deviation 0.132 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 5 (Week 6) | -0.02 U/L/mg/dL | Standard Deviation 0.147 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 6 (Week 12) | -0.02 U/L/mg/dL | Standard Deviation 0.108 |
| TMX-049 200 mg QD | Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase) | Visit 4 (Week 2) | -0.01 U/L/mg/dL | Standard Deviation 0.152 |
Secondary
Changes in Serum Uric Acid (sUA)
Serum Uric Acid from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured in order to explore the sUA (Serum Uric Acid) lowering effect in DKD (diabetic kidney disease) patients and the relationship between sUA and efficacy to DKD.
Time frame: Baseline and Week 2, 6, 12, 16 (Follow-up)
Population: Modified Intention-to-Treat (mITT) Population consisted of all randomized subjects who had at least 1 post-randomization UACR assessment. Subjects in the mITT Population were analyzed according to their randomized treatment
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| TMX-049 Placebo | Changes in Serum Uric Acid (sUA) | Visit 4 (Week 2) | -0.03 mg/dL | Standard Error 0.238 |
| TMX-049 Placebo | Changes in Serum Uric Acid (sUA) | Visit 5 (Week 6) | -0.22 mg/dL | Standard Error 0.256 |
| TMX-049 Placebo | Changes in Serum Uric Acid (sUA) | Visit 6/ET (Week 12) | -0.07 mg/dL | Standard Error 0.269 |
| TMX-049 Placebo | Changes in Serum Uric Acid (sUA) | Visit 7/Follow up (Week 16) | 0.21 mg/dL | Standard Error 0.19 |
| TMX-049 40 mg QD | Changes in Serum Uric Acid (sUA) | Visit 7/Follow up (Week 16) | -0.13 mg/dL | Standard Error 0.188 |
| TMX-049 40 mg QD | Changes in Serum Uric Acid (sUA) | Visit 4 (Week 2) | -2.57 mg/dL | Standard Error 0.24 |
| TMX-049 40 mg QD | Changes in Serum Uric Acid (sUA) | Visit 6/ET (Week 12) | -2.51 mg/dL | Standard Error 0.266 |
| TMX-049 40 mg QD | Changes in Serum Uric Acid (sUA) | Visit 5 (Week 6) | -2.54 mg/dL | Standard Error 0.252 |
| TMX-049 200 mg QD | Changes in Serum Uric Acid (sUA) | Visit 7/Follow up (Week 16) | -0.33 mg/dL | Standard Error 0.187 |
| TMX-049 200 mg QD | Changes in Serum Uric Acid (sUA) | Visit 5 (Week 6) | -3.34 mg/dL | Standard Error 0.251 |
| TMX-049 200 mg QD | Changes in Serum Uric Acid (sUA) | Visit 6/ET (Week 12) | -3.30 mg/dL | Standard Error 0.265 |
| TMX-049 200 mg QD | Changes in Serum Uric Acid (sUA) | Visit 4 (Week 2) | -3.54 mg/dL | Standard Error 0.234 |
Comparison: For Week 12 (visit of the primary outcome), an ANCOVA model with treatment, randomization strata of UACR levels as independent variables is fitted. The last observation carried forward imputation was used for missing data.p-value: <0.000195% CI: [-3.13, -1.74]ANCOVA
Comparison: For Week 12 (visit of the primary outcome), an ANCOVA model with treatment, randomization strata of UACR levels as independent variables is fitted. The last observation carried forward imputation was used for missing data.p-value: <0.000195% CI: [-3.91, -2.54]ANCOVA
Secondary
Changes in Urinary Albumin-to-Creatinine Ratio (UACR)
Urinary Albumin-to-Creatinine Ratio from Baseline to Weeks 2, 6, 12/early termination, and 16 (Follow-up) were measured.
Time frame: Baseline and Week 2, 6, 12, 16 (Follow-up)
Population: Modified Intention-to-Treat (mITT) Population consisted of all randomized subjects who had at least 1 post-randomization UACR assessment. Subjects in the mITT Population were analyzed according to their randomized treatment
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| TMX-049 Placebo | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 4 (Week 2) | 25.44 mg/g | Standard Error 69.166 |
| TMX-049 Placebo | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 5 (Week 6) | -81.90 mg/g | Standard Error 68.156 |
| TMX-049 Placebo | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 6/ET (Week 12) | 61.92 mg/g | Standard Error 92.291 |
| TMX-049 Placebo | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 7/ Follow up (Week 16) | 72.07 mg/g | Standard Error 90.045 |
| TMX-049 40 mg QD | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 7/ Follow up (Week 16) | 58.31 mg/g | Standard Error 88.825 |
| TMX-049 40 mg QD | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 4 (Week 2) | 53.88 mg/g | Standard Error 68.229 |
| TMX-049 40 mg QD | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 6/ET (Week 12) | -40.10 mg/g | Standard Error 91.041 |
| TMX-049 40 mg QD | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 5 (Week 6) | -30.37 mg/g | Standard Error 67.233 |
| TMX-049 200 mg QD | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 7/ Follow up (Week 16) | -8.27 mg/g | Standard Error 88.439 |
| TMX-049 200 mg QD | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 5 (Week 6) | -86.12 mg/g | Standard Error 66.94 |
| TMX-049 200 mg QD | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 6/ET (Week 12) | -135.57 mg/g | Standard Error 90.645 |
| TMX-049 200 mg QD | Changes in Urinary Albumin-to-Creatinine Ratio (UACR) | Visit 4 (Week 2) | -86.20 mg/g | Standard Error 67.932 |
Comparison: For Week 12 (visit of the primary outcome), an ANCOVA model with treatment, randomization strata of UACR levels as independent variables is fitted. The last observation carried forward imputation was used for missing data.p-value: 0.395595% CI: [-338.81, 134.78]ANCOVA
Comparison: For Week 12 (visit of the primary outcome), ANCOVA model with treatment, randomization strata of UACR levels as independent variables is fitted. The last observation carried forward imputation was used for missing data.p-value: 0.099195% CI: [-432.73, 37.75]ANCOVA
Secondary
Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio
Changes in Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio were measured. Subject with greater than 30% reduction is estimated as responder, less than or equal to 30% reduction is estimated as non-responder.
Time frame: 16 Weeks
Population: Modified Intention-to-Treat (mITT) Population consisted of all randomized subjects who had at least 1 post-randomization UACR assessment. Subjects in the mITT Population were analyzed according to their randomized treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TMX-049 Placebo | Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio | Responder | 10 Participants |
| TMX-049 Placebo | Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio | Non-responder | 32 Participants |
| TMX-049 40 mg QD | Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio | Responder | 14 Participants |
| TMX-049 40 mg QD | Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio | Non-responder | 29 Participants |
| TMX-049 200 mg QD | Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio | Responder | 19 Participants |
| TMX-049 200 mg QD | Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio | Non-responder | 25 Participants |
Comparison: Odds ratio, 95% CLs, and p-values are obtained from logistic regression model adjusting for treatment group, randomization strata of Baseline sUA (\<6.0 vs ≥6.0 mg/dL) and Baseline UACR (200 to \<300 mg/g vs 300 to ≤3000 mg/g), Baseline UACR and Baseline sUA levels. Odds ratio for a baseline covariate is the ratio of odds over one unit increase of the covariate and it is assumed constant. P-value represents the statistical significance level of odds ratio differing from 1.p-value: 0.2791Regression, Logistic
Comparison: Odds ratio, 95% CLs, and p-values are obtained from logistic regression model adjusting for treatment group, randomization strata of Baseline sUA (\<6.0 vs ≥6.0 mg/dL) and Baseline UACR (200 to \<300 mg/g vs 300 to ≤3000 mg/g), Baseline UACR and Baseline sUA levels. Odds ratio for a baseline covariate is the ratio of odds over one unit increase of the covariate and it is assumed constant. P-value represents the statistical significance level of odds ratio differing from 1.p-value: 0.0507Regression, Logistic