Phase 2 Study of TMX-049 in Subjects With Type 2 Diabetes and Albuminuria

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase 2 Study to Assess Safety, Tolerability, and Renal Effects of TMX-049 in Subjects With Type 2 Diabetes and Albuminuria

Conditions
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Diabetic Kidney Disease

Intervention / Treatment
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* Drug: TMX-049
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TMX-049 40 mg QD (Once Daily)<br>TMX-049: 40 mg of TMX-049 to be taken orally, once daily | Drug: TMX-049<br>* A certain dose of TMX-049 to be taken orally, once daily<br>|
| Experimental: TMX-049 200 mg QD (Once Daily)<br>TMX-049: 200 mg of TMX-049 to be taken orally, once daily | Drug: TMX-049<br>* A certain dose of TMX-049 to be taken orally, once daily<br>|
| Placebo Comparator: TMX-049 Placebo<br> | Drug: Placebo<br>* Matching placebo to be taken orally, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 2, 6, 12, 16 (Follow-up) | 
| 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. | Baseline and Week 2, 6, 12, 16 (Follow-up) | 
| 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. | Baseline and Week 2, 6, 12, 16 (Follow-up) | 
| 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. | 16 Weeks | 
| 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. | 16 Weeks | 
| 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. | 16 Weeks | 
| 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. | 16 Weeks | 
| 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. | 16 Weeks | 
| 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. | 16 Weeks | 
| 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. | 16 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Kidney Disease, XO inhibitor, UACR