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Prospective, Randomized, Double-Blind, Placebo-Controlled Multicenter Study. The objective of the study is to evaluate the efficacy and safety of once daily administration of atrasentan tablets (low dose and high dose) compared to placebo in reducing residual albuminuria in Type 2 diabetic patients with nephropathy who are treated with the maximum tolerated labeled dose of a Renin Angiotensin System (RAS) inhibitor. If the patient is already receiving a maximum tolerated labeled daily dose of RAS inhibitor and a diuretic, he/she will complete 4 weeks of the Run-in Period on a dose that has not been adjusted. If the patient is currently not receiving a maximum labeled daily dose of a RAS inhibitor then the dose will be titrated up to the maximum tolerated labeled dose over the course of 4 to 8 weeks during the Run-in Period. It is expected that subjects not receiving a diuretic will have a diuretic added or titrated during this period to maximize RAS inhibition. Following titration to the maximum tolerated labeled dose, the patient will complete an additional 4 weeks of Run-In Period on an unchanged doses of RAS inhibitor and diuretics, unless medically contraindicated. The randomization will be stratified based on country where subjects are enrolled into the study, and the Week -1 Urinary Albumin to Creatinine Ratio (UACR) levels (< or = 1000 mg/g [113 mg/mmol], or > 1000 mg/g [113 mg/mmol]). Within each stratum, subjects will be randomly assigned in a 1:2:2 ratio to one of the following blinded treatment groups: Group A - Placebo once daily (QD) Group B - low dose atrasentan QD Group C - high dose atrasentan QD After the 12 weeks of study drug treatment, subjects will be followed up to 30 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A - Placebo QD | Placebo Comparator |
| |
| Group B - Low dose Atrasentan QD | Active Comparator |
| |
| Group C - High dose Atrasentan QD | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atrasentan | Drug | Subjects will take two tablets daily of either low dose Atrasentan QD or high dose Atrasentan QD for 12 weeks during the treatment period. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline to Week 12 in Urinary Albumin to Creatinine Ratio (UACR) | Every two weeks for 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Differences in change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR) | Every two weeks for 12 weeks | |
| Differences in change from baseline to each post baseline measure for EQ-5D Index Score | Once a month for 3 months |
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Inclusion Criteria:
Patient is > or = 18 years old.
Patient has Type 2 diabetes and has been treated with at least one anti hyperglycemic medication within the 12 months prior to the Screening Period.
Patient is currently receiving an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin II receptor blocker (ARB) (Renin Angiotensin System (RAS) inhibitor).
For entry in the Run-in Period the patient must satisfy the following criteria based on the Screening laboratory values:
For entry in the Treatment Period the patient must satisfy the following criteria based on the last visit of the Run-in Period laboratory values:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Blai Coll, MD | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Site Reference ID/Investigator# 46345 | Pell City | Alabama | 35128 | United States | ||
| Site Reference ID/Investigator# 46035 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37716952 | Derived | Smeijer JD, Kohan DE, Rossing P, Correa-Rotter R, Liew A, Tang SCW, de Zeeuw D, Gansevoort RT, Ju W, Lambers Heerspink HJ. Insulin resistance, kidney outcomes and effects of the endothelin receptor antagonist atrasentan in patients with type 2 diabetes and chronic kidney disease. Cardiovasc Diabetol. 2023 Sep 16;22(1):251. doi: 10.1186/s12933-023-01964-8. | |
| 28756065 |
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|
| Placebo | Drug | Subjects will take two tablets daily of placebo QD for 12 weeks during the treatment period. |
|
| Differences in change from baseline to each post baseline measure for each of the Kidney Disease Quality of Life (KDQOL) Kidney Disease Targeted Scales | Once a month for 3 months |
| Tempe |
| Arizona |
| 85284 |
| United States |
| Site Reference ID/Investigator# 46016 | Azusa | California | 91702 | United States |
| Site Reference ID/Investigator# 45992 | Chula Vista | California | 91910 | United States |
| Site Reference ID/Investigator# 46000 | La Mesa | California | 91942 | United States |
| Site Reference ID/Investigator# 46038 | Lincoln | California | 95648 | United States |
| Site Reference ID/Investigator# 45994 | Long Beach | California | 90806 | United States |
| Site Reference ID/Investigator# 45998 | Los Angeles | California | 90022 | United States |
| Site Reference ID/Investigator# 47584 | Los Gatos | California | 95032 | United States |
| Site Reference ID/Investigator# 64465 | National City | California | 91950 | United States |
| Site Reference ID/Investigator# 65862 | Orange | California | 92868 | United States |
| Site Reference ID/Investigator# 46019 | Riverside | California | 92505 | United States |
| Site Reference ID/Investigator# 46110 | Salinas | California | 93901 | United States |
| Site Reference ID/Investigator# 46017 | Yuba City | California | 95991 | United States |
| Site Reference ID/Investigator# 46662 | Westminster | Colorado | 80031 | United States |
| Site Reference ID/Investigator# 46033 | Coral Gables | Florida | 33134 | United States |
| Site Reference ID/Investigator# 45989 | Hialeah | Florida | 33012 | United States |
| Site Reference ID/Investigator# 46667 | Lauderdale Lakes | Florida | 33313 | United States |
| Site Reference ID/Investigator# 46123 | Miami | Florida | 33135 | United States |
| Site Reference ID/Investigator# 46115 | Ocala | Florida | 34471 | United States |
| Site Reference ID/Investigator# 46664 | Pembroke Pines | Florida | 33027 | United States |
| Site Reference ID/Investigator# 46031 | Pembroke Pines | Florida | 33028 | United States |
| Site Reference ID/Investigator# 46040 | Pembroke Pines | Florida | 33028 | United States |
| Site Reference ID/Investigator# 46122 | Port Charlotte | Florida | 33952 | United States |
| Site Reference ID/Investigator# 46015 | West Palm Beach | Florida | 33401 | United States |
| Site Reference ID/Investigator# 50482 | Jonesboro | Georgia | 30236 | United States |
| Site Reference ID/Investigator# 46034 | Meridian | Idaho | 83642 | United States |
| Site Reference ID/Investigator# 46666 | Chicago | Illinois | 60616 | United States |
| Site Reference ID/Investigator# 45996 | Evergreen Park | Illinois | 60805 | United States |
| Site Reference ID/Investigator# 46002 | Gurnee | Illinois | 60031 | United States |
| Site Reference ID/Investigator# 46111 | Shreveport | Louisiana | 71101 | United States |
| Site Reference ID/Investigator# 46030 | Oxon Hill | Maryland | 20745 | United States |
| Site Reference ID/Investigator# 45991 | Rockville | Maryland | 20852 | United States |
| Site Reference ID/Investigator# 46025 | Novi | Michigan | 48374 | United States |
| Site Reference ID/Investigator# 46023 | Brooklyn Center | Minnesota | 55430 | United States |
| Site Reference ID/Investigator# 46062 | Farmington | Missouri | 63640 | United States |
| Site Reference ID/Investigator# 48942 | Omaha | Nebraska | 68131-3403 | United States |
| Site Reference ID/Investigator# 46349 | Omaha | Nebraska | 68131 | United States |
| Site Reference ID/Investigator# 46116 | Las Vegas | Nevada | 89106 | United States |
| Site Reference ID/Investigator# 50483 | Albany | New York | 12206 | United States |
| Site Reference ID/Investigator# 68328 | New Hyde Park | New York | 11042 | United States |
| Site Reference ID/Investigator# 65863 | Asheville | North Carolina | 28801 | United States |
| Site Reference ID/Investigator# 50529 | Greensboro | North Carolina | 27408 | United States |
| Site Reference ID/Investigator# 46129 | Greenville | North Carolina | 27834 | United States |
| Site Reference ID/Investigator# 46022 | Morehead City | North Carolina | 28557 | United States |
| Site Reference ID/Investigator# 46224 | Doylestown | Pennsylvania | 18901 | United States |
| Site Reference ID/Investigator# 46028 | Orangeburg | South Carolina | 29118 | United States |
| Site Reference ID/Investigator# 46702 | Orangeburg | South Carolina | 29118 | United States |
| Site Reference ID/Investigator# 46024 | Greenville | Texas | 75402 | United States |
| Site Reference ID/Investigator# 46228 | Houston | Texas | 77004 | United States |
| Site Reference ID/Investigator# 47068 | Houston | Texas | 77004 | United States |
| Site Reference ID/Investigator# 64464 | Houston | Texas | 77054 | United States |
| Site Reference ID/Investigator# 64483 | Mission | Texas | 78572 | United States |
| Site Reference ID/Investigator# 46348 | San Antonio | Texas | 78215 | United States |
| Site Reference ID/Investigator# 46063 | San Antonio | Texas | 78229-4801 | United States |
| Site Reference ID/Investigator# 68486 | San Antonio | Texas | 78229 | United States |
| Site Reference ID/Investigator# 46669 | Bennington | Vermont | 05201 | United States |
| Site Reference ID/Investigator# 46026 | Alexandria | Virginia | 22304 | United States |
| Site Reference ID/Investigator# 46027 | Fairfax | Virginia | 22030 | United States |
| Site Reference ID/Investigator# 67762 | Kitchener | N2H 5Z8 | Canada |
| Site Reference ID/Investigator# 50526 | Sarnia | N7T 4X3 | Canada |
| Site Reference ID/Investigator# 50525 | Thornhill | L4J 8L7 | Canada |
| Site Reference ID/Investigator# 47067 | Caguas | 00725 | Puerto Rico |
| Site Reference ID/Investigator# 50522 | Manati | 00674 | Puerto Rico |
| Site Reference ID/Investigator# 46352 | Ponce | 00717-1322 | Puerto Rico |
| Site Reference ID/Investigator# 46351 | Ponce | 00717-2075 | Puerto Rico |
| Site Reference ID/Investigator# 46133 | Ponce | 00717 | Puerto Rico |
| Site Reference ID/Investigator# 46131 | Rio Piedras | 00935 | Puerto Rico |
| Site Reference ID/Investigator# 46132 | San Juan | 00918 | Puerto Rico |
| Site Reference ID/Investigator# 46230 | Santurce | 00909-2244 | Puerto Rico |
| Site Reference ID/Investigator# 51566 | Taichung | 40447 | Taiwan |
| Site Reference ID/Investigator# 51567 | Taichung | 40705 | Taiwan |
| Lin CW, Mostafa NM, L Andress D, J Brennan J, Klein CE, Awni WM. Relationship Between Atrasentan Concentrations and Urinary Albumin to Creatinine Ratio in Western and Japanese Patients With Diabetic Nephropathy. Clin Ther. 2018 Feb;40(2):242-251. doi: 10.1016/j.clinthera.2017.07.011. Epub 2017 Jul 27. |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D003928 | Diabetic Nephropathies |
| D011507 | Proteinuria |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D014555 | Urination Disorders |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077868 | Atrasentan |
| ID | Term |
|---|---|
| D052117 | Benzodioxoles |
| D004149 | Dioxoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011759 | Pyrrolidines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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