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

Diabetic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03449199
• Other study ID #: TMX-049DN-201
• Status: Completed
• Phase: Phase 2
• Start date: April 10, 2018
• Est. completion date: June 4, 2019

Study information

• Verified date: August 2022
• Source: Teijin America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: June 4, 2019
• Est. primary completion date: May 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Albuminuria
• Diabetic Kidney Disease
• Diabetic Nephropathies
• Kidney Diseases

Intervention

Drug:
• TMX-049
A certain dose of TMX-049 to be taken orally, once daily
• Placebo
Matching placebo to be taken orally, once daily

Locations

Country	Name	City	State
United States	Albany Medical College, Division of Community Endocinology	Albany	New York
United States	Comprehensive Research Institute	Alhambra	California
United States	Community Clinical Research Center	Anderson	Indiana
United States	Community Hospital of Anderson and Madison County, Inc.	Anderson	Indiana
United States	Randolph Health Internal Medicine	Asheboro	North Carolina
United States	Nephrology Associates, PC	Augusta	Georgia
United States	Southeastern Clinical Research Institute	Augusta	Georgia
United States	Ochsner Clinic Foundation, Baton Rouge	Baton Rouge	Louisiana
United States	University Diabetes & Endocrine Consultants	Chattanooga	Tennessee
United States	California Kidney Specialists	Covina	California
United States	Texas Health Physicians Group	Dallas	Texas
United States	Iowa Kidney Physicians	Des Moines	Iowa
United States	Associate in Endocrinology	Elgin	Illinois
United States	AKDHC Medical Research Services, LLC	Flagstaff	Arizona
United States	Aa Mrc Llc	Flint	Michigan
United States	Elite Research Center LLC	Flint	Michigan
United States	Endocrine Consultants of Mid Michigan	Flint	Michigan
United States	Rockwood Medical Clinic	Fort Worth	Texas
United States	The Medical Group of Texas	Fort Worth	Texas
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Endocrine Associates	Houston	Texas
United States	Houston Nephrology Research	Houston	Texas
United States	Juno Research, LLC	Houston	Texas
United States	Pioneer Research Solutions INC	Houston	Texas
United States	The Endocrine Center	Houston	Texas
United States	Knoxville Kidney Center, PLLC	Knoxville	Tennessee
United States	Detweiler Family Medicine & Associates, PC	Lansdale	Pennsylvania
United States	Torrance Clinical Research Institute, Inc.	Lomita	California
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	My Kidney Center, LLC.	Manhattan	Kansas
United States	Solaris Clinical Research, Llc	Meridian	Idaho
United States	Aventiv Research Inc.	Mesa	Arizona
United States	Leon Medical Research	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami Lakes	Florida
United States	Carteret Medical Group	Morehead City	North Carolina
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Endocrine Associates of Florida, P.A.	Ocoee	Florida
United States	Synexus Clinical Research US, Inc. Centennial Health, PC	Oklahoma City	Oklahoma
United States	Diabetes Associates Medical Group	Orange	California
United States	Four Rivers Clincial Research	Paducah	Kentucky
United States	Desert Oasis Healthcare Medical Group	Palm Springs	California
United States	Pines Care Research Center	Pembroke Pines	Florida
United States	Hanson Clinical Research Center	Port Charlotte	Florida
United States	Seacost Kidney & Hypertension Specialists	Portsmouth	New Hampshire
United States	Biolab Research LLC	Rockville	Maryland
United States	University of Utah School of Medicine	Salt Lake City	Utah
United States	BFHC Research	San Antonio	Texas
United States	Clinical Advancement Center, PLLC	San Antonio	Texas
United States	California Kidney Specialists	San Dimas	California
United States	North America Research Institute	San Dimas	California
United States	Carl R. Meisner Medical Clinic, PLLC	Sugar Land	Texas
United States	Cotton O'Neil Clinical Research Center	Topeka	Kansas
United States	Iowa Diabetes and Endocrinology Research Center	West Des Moines	Iowa
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina
United States	Brookview Hills Research Associates, LLC	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Teijin America, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline and Week 12
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.	Baseline and Week 2, 6, 12, 16 (Follow-up)
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.	Baseline and Week 2, 6, 12, 16 (Follow-up)
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.	Baseline and Week 2, 6, 12, 16 (Follow-up)
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.	16 Weeks
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.	16 Weeks
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.	16 Weeks
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.	16 Weeks
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.	16 Weeks
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.	16 Weeks
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.	16 Weeks