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

Phase 2
Completed
Conditions
Diabetic Kidney Disease
Interventions
Drug: Placebo
Registration Number
NCT03449199
Lead Sponsor
Teijin America, Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
130
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TMX-049 PlaceboPlacebo-
TMX-049 200 mg QD (Once Daily)TMX-049TMX-049: 200 mg of TMX-049 to be taken orally, once daily
TMX-049 40 mg QD (Once Daily)TMX-049TMX-049: 40 mg of TMX-049 to be taken orally, once daily
Primary Outcome Measures
NameTimeMethod
Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at Week 12Baseline 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 Outcome Measures
NameTimeMethod
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.

Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio16 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 (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.

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 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.

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 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 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 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.

Trial Locations

Locations (54)

AKDHC Medical Research Services, LLC

🇺🇸

Flagstaff, Arizona, United States

Aventiv Research Inc.

🇺🇸

Mesa, Arizona, United States

Comprehensive Research Institute

🇺🇸

Alhambra, California, United States

California Kidney Specialists

🇺🇸

San Dimas, California, United States

Torrance Clinical Research Institute, Inc.

🇺🇸

Lomita, California, United States

Valley Clinical Trials, Inc.

🇺🇸

Northridge, California, United States

Diabetes Associates Medical Group

🇺🇸

Orange, California, United States

Desert Oasis Healthcare Medical Group

🇺🇸

Palm Springs, California, United States

North America Research Institute

🇺🇸

San Dimas, California, United States

San Marcus Research Clinic, Inc.

🇺🇸

Miami Lakes, Florida, United States

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AKDHC Medical Research Services, LLC
🇺🇸Flagstaff, Arizona, United States

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