Clinical trial NCT03449199: Phase 2 Study of TMX-049 in Subjects With Type 2 Diabetes and Albuminuria
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Kidney Disease
Keywords: Diabetic Kidney Disease
XO inhibitor
UACR
Lead sponsor: Teijin America, Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-28
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Changes in Log-transformed Urinary Albumin-to-creatinine Ratio (UACR) at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Changes in Estimated Glomerular Filtration Rate (GFR)
timeFrame: Baseline and Week 2, 6, 12, 16 (Follow-up)
measure: Changes in Serum Uric Acid (sUA)
timeFrame: Baseline and Week 2, 6, 12, 16 (Follow-up)
measure: Changes in Urinary Albumin-to-Creatinine Ratio (UACR)
timeFrame: Baseline and Week 2, 6, 12, 16 (Follow-up)
measure: Proportion of Subjects With a Greater Than 30% Reduction From Baseline to Week 12 in Urinary Albumin-to-Creatinine Ratio
timeFrame: 16 Weeks
measure: Changes in Exploratory Blood Biomarkers (C Reactive Protein)
timeFrame: 16 Weeks
measure: Changes in Exploratory Blood Biomarkers (Soluble TNF Receptor Type I)
timeFrame: 16 Weeks
measure: Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Fatty Acid Binding Protein 1)
timeFrame: 16 Weeks
measure: Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Hydroxy Deoxyguanosine)
timeFrame: 16 Weeks
measure: Changes in Exploratory Renal Biomarkers (Creatinine-Corrected Kidney Injury Molecule-1)
timeFrame: 16 Weeks
measure: Changes in Exploratory Renal Biomarkers (Creatinine-Corrected N-acetyl-beta-D-glucosaminidase)
timeFrame: 16 Weeks
Other outcomes:
Locations:
city: Flagstaff
country: United States
facility: AKDHC Medical Research Services, LLC
state: Arizona
city: Mesa
country: United States
facility: Aventiv Research Inc.
state: Arizona
city: Alhambra
country: United States
facility: Comprehensive Research Institute
state: California
city: Covina
country: United States
facility: California Kidney Specialists
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute, Inc.
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Orange
country: United States
facility: Diabetes Associates Medical Group
state: California
city: Palm Springs
country: United States
facility: Desert Oasis Healthcare Medical Group
state: California
city: San Dimas
country: United States
facility: California Kidney Specialists
state: California
city: San Dimas
country: United States
facility: North America Research Institute
state: California
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Miami
country: United States
facility: Leon Medical Research
state: Florida
city: Ocoee
country: United States
facility: Endocrine Associates of Florida, P.A.
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Care Research Center
state: Florida
city: Port Charlotte
country: United States
facility: Hanson Clinical Research Center
state: Florida
city: Augusta
country: United States
facility: Nephrology Associates, PC
state: Georgia
city: Augusta
country: United States
facility: Southeastern Clinical Research Institute
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Meridian
country: United States
facility: Solaris Clinical Research, Llc
state: Idaho
city: Elgin
country: United States
facility: Associate in Endocrinology
state: Illinois
city: Anderson
country: United States
facility: Community Clinical Research Center
state: Indiana
city: Anderson
country: United States
facility: Community Hospital of Anderson and Madison County, Inc.
state: Indiana
city: Des Moines
country: United States
facility: Iowa Kidney Physicians
state: Iowa
city: West Des Moines
country: United States
facility: Iowa Diabetes and Endocrinology Research Center
state: Iowa
city: Manhattan
country: United States
facility: My Kidney Center, LLC.
state: Kansas
city: Topeka
country: United States
facility: Cotton O'Neil Clinical Research Center
state: Kansas
city: Paducah
country: United States
facility: Four Rivers Clincial Research
state: Kentucky
city: Baton Rouge
country: United States
facility: Ochsner Clinic Foundation, Baton Rouge
state: Louisiana
city: Rockville
country: United States
facility: Biolab Research LLC
state: Maryland
city: Flint
country: United States
facility: Aa Mrc Llc
state: Michigan
city: Flint
country: United States
facility: Elite Research Center LLC
state: Michigan
city: Flint
country: United States
facility: Endocrine Consultants of Mid Michigan
state: Michigan
city: Portsmouth
country: United States
facility: Seacost Kidney & Hypertension Specialists
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical College, Division of Community Endocinology
state: New York
city: Asheboro
country: United States
facility: Randolph Health Internal Medicine
state: North Carolina
city: Morehead City
country: United States
facility: Carteret Medical Group
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Brookview Hills Research Associates, LLC
state: North Carolina
city: Oklahoma City
country: United States
facility: Synexus Clinical Research US, Inc. Centennial Health, PC
state: Oklahoma
city: Lansdale
country: United States
facility: Detweiler Family Medicine & Associates, PC
state: Pennsylvania
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Consultants
state: Tennessee
city: Knoxville
country: United States
facility: Knoxville Kidney Center, PLLC
state: Tennessee
city: Dallas
country: United States
facility: Texas Health Physicians Group
state: Texas
city: Fort Worth
country: United States
facility: The Medical Group of Texas
state: Texas
city: Fort Worth
country: United States
facility: Rockwood Medical Clinic
state: Texas
city: Houston
country: United States
facility: Endocrine Associates
state: Texas
city: Houston
country: United States
facility: Juno Research, LLC
state: Texas
city: Houston
country: United States
facility: The Endocrine Center
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions INC
state: Texas
city: Houston
country: United States
facility: Houston Nephrology Research
state: Texas
city: San Antonio
country: United States
facility: Clinical Advancement Center, PLLC
state: Texas
city: San Antonio
country: United States
facility: BFHC Research
state: Texas
city: Sugar Land
country: United States
facility: Carl R. Meisner Medical Clinic, PLLC
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine
state: Utah
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
Study officials:
affiliation: Covance
name: Michael Cressman, D.O.
role: STUDY_DIRECTOR
References:
citation: Bakris GL, Mikami H, Hirata M, Nakajima A, Cressman MD. A Non-purine Xanthine Oxidoreductase Inhibitor Reduces Albuminuria in Patients with DKD: A Randomized Controlled Trial. Kidney360. 2021 Jun 30;2(8):1240-1250. doi: 10.34067/KID.0001672021. eCollection 2021 Aug 26.