Evaluate the Efficacy and Safety of Once Daily Administration of Atrasentan Tablets (Low and High) 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

NCT01356849 | Completed Phase 2 DMC

• 1 other identifier: M11-350
• Study Type: interventional
• Target: 149
• Locations: 4 countries
• Sites: 72

Brief Summary

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.

Conditions

Chronic Kidney Disease; Diabetic Nephropathy

Keywords

Endothelin Receptor Antagonists; Proteinuria

Outcome Measures

Primary Outcomes (1)

• Change from baseline to Week 12 in Urinary Albumin to Creatinine Ratio (UACR)

  Every two weeks for 12 weeks

Secondary Outcomes (3)

• 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

• 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

Study Arms (3)

Group A - Placebo QD

PLACEBO COMPARATOR

Drug: Placebo

Group B - Low dose Atrasentan QD

ACTIVE COMPARATOR

Drug: Atrasentan

Group C - High dose Atrasentan QD

ACTIVE COMPARATOR

Drug: Atrasentan

Interventions

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.

Also known as: ABT-627

Group B - Low dose Atrasentan QD; Group C - High dose Atrasentan QD

Placebo DRUG

Subjects will take two tablets daily of placebo QD for 12 weeks during the treatment period.

Group A - Placebo QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Estimated glomerular filtration rate (eGFR) ≥ 30 and ≤ 75 mL/min/1.73m2 by Epidemiology Collaboration (EPI) formula
• Urinary Albumin to Creatinine Ratio (UACR) \> or = 300 and \< or = 3500 mg/g as determined by the geometric mean of the two morning void urine specimens obtained at the Screening visit (UACR \> or = 34 mg/mmol and \< or = 396 mg/mmol)
• Serum albumin \> or = 3.0 g/dL (30 g/L) - B-type Natriuretic Peptide (BNP) \< or = 200 pg/mL (57.8 pmol/L) \* Negative serum pregnancy test for female patients
• Systolic Blood Pressure (SBP) \> or = 110 mmHg and \< or = 180 mmHg
• Glucosylated hemoglobin A1c (HbA1c) \< or = 12%
• 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:
• Renin Angiotensin System (RAS) inhibitor at maximum tolerated labeled dose for the previous 4 weeks with no adjustments of dose
• Diuretic at any dose unless medically contraindicated (with the exception of loop diuretics \> or = 120 mg QD of furosemide or \> or = 3.0 mg QD of bumetanide or \> or = 150 mg QD of ethacrynic acid or \> or = 60 mg QD of torasemide)
• Urinary Albumin to Creatinine Ratio (UACR) \> or = 200 and \< or = 3500 mg/g as determined by the median of the three morning void urine specimens obtained prior to the Week -1 visit (UACR \> or = 23 mg/mmol and \< or = 396 mg/mmol)
• Systolic blood pressure (SBP) \> or = 110 mmHg and \< or = 160 mmHg
• Serum Potassium \< or = 5.5 mEq/L (5.5 mmol/L)

You may not qualify if:

• Patient has a history of moderate or severe edema, facial edema unrelated to trauma, or a history of myxedema in the prior 6 months to Screening.
• Patient is receiving loop diuretics \> or = 120 mg QD of furosemide or \> or = 3.0 mg QD of bumetanide or \> or = 150 mg QD of ethacrynic acid or \> or = 60 mg QD of torasemide.
• Patient has a history of pulmonary edema.
• Patient has a history of pulmonary hypertension, or any lung diseases requiring oxygen therapy (i.e., chronic obstructive pulmonary disease, emphysema, pulmonary fibrosis).
• Patient has a history of orthostatic hypotension within the past 6 months as defined by the presence of a supine-to-standing blood pressure decrease \> or = 20 mmHg systolic or \> or = 10 mmHg diastolic within 3 minutes of standing.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (72)

Site Reference ID/Investigator# 46345

Pell City, Alabama, 35128, United States

Location

Site Reference ID/Investigator# 46035

Tempe, Arizona, 85284, United States

Location

Site Reference ID/Investigator# 46016

Azusa, California, 91702, United States

Location

Site Reference ID/Investigator# 45992

Chula Vista, California, 91910, United States

Location

Site Reference ID/Investigator# 46000

La Mesa, California, 91942, United States

Location

Site Reference ID/Investigator# 46038

Lincoln, California, 95648, United States

Location

Site Reference ID/Investigator# 45994

Long Beach, California, 90806, United States

Location

Site Reference ID/Investigator# 45998

Los Angeles, California, 90022, United States

Location

Site Reference ID/Investigator# 47584

Los Gatos, California, 95032, United States

Location

Site Reference ID/Investigator# 64465

National City, California, 91950, United States

Location

Site Reference ID/Investigator# 65862

Orange, California, 92868, United States

Location

Site Reference ID/Investigator# 46019

Riverside, California, 92505, United States

Location

Site Reference ID/Investigator# 46110

Salinas, California, 93901, United States

Location

Site Reference ID/Investigator# 46017

Yuba City, California, 95991, United States

Location

Site Reference ID/Investigator# 46662

Westminster, Colorado, 80031, United States

Location

Site Reference ID/Investigator# 46033

Coral Gables, Florida, 33134, United States

Location

Site Reference ID/Investigator# 45989

Hialeah, Florida, 33012, United States

Location

Site Reference ID/Investigator# 46667

Lauderdale Lakes, Florida, 33313, United States

Location

Site Reference ID/Investigator# 46123

Miami, Florida, 33135, United States

Location

Site Reference ID/Investigator# 46115

Ocala, Florida, 34471, United States

Location

Site Reference ID/Investigator# 46664

Pembroke Pines, Florida, 33027, United States

Location

Site Reference ID/Investigator# 46031

Pembroke Pines, Florida, 33028, United States

Location

Site Reference ID/Investigator# 46040

Pembroke Pines, Florida, 33028, United States

Location

Site Reference ID/Investigator# 46122

Port Charlotte, Florida, 33952, United States

Location

Site Reference ID/Investigator# 46015

West Palm Beach, Florida, 33401, United States

Location

Site Reference ID/Investigator# 50482

Jonesboro, Georgia, 30236, United States

Location

Site Reference ID/Investigator# 46034

Meridian, Idaho, 83642, United States

Location

Site Reference ID/Investigator# 46666

Chicago, Illinois, 60616, United States

Location

Site Reference ID/Investigator# 45996

Evergreen Park, Illinois, 60805, United States

Location

Site Reference ID/Investigator# 46002

Gurnee, Illinois, 60031, United States

Location

Site Reference ID/Investigator# 46111

Shreveport, Louisiana, 71101, United States

Location

Site Reference ID/Investigator# 46030

Oxon Hill, Maryland, 20745, United States

Location

Site Reference ID/Investigator# 45991

Rockville, Maryland, 20852, United States

Location

Site Reference ID/Investigator# 46025

Novi, Michigan, 48374, United States

Location

Site Reference ID/Investigator# 46023

Brooklyn Center, Minnesota, 55430, United States

Location

Site Reference ID/Investigator# 46062

Farmington, Missouri, 63640, United States

Location

Site Reference ID/Investigator# 48942

Omaha, Nebraska, 68131-3403, United States

Location

Site Reference ID/Investigator# 46349

Omaha, Nebraska, 68131, United States

Location

Site Reference ID/Investigator# 46116

Las Vegas, Nevada, 89106, United States

Location

Site Reference ID/Investigator# 50483

Albany, New York, 12206, United States

Location

Site Reference ID/Investigator# 68328

New Hyde Park, New York, 11042, United States

Location

Site Reference ID/Investigator# 65863

Asheville, North Carolina, 28801, United States

Location

Site Reference ID/Investigator# 50529

Greensboro, North Carolina, 27408, United States

Location

Site Reference ID/Investigator# 46129

Greenville, North Carolina, 27834, United States

Location

Site Reference ID/Investigator# 46022

Morehead City, North Carolina, 28557, United States

Location

Site Reference ID/Investigator# 46224

Doylestown, Pennsylvania, 18901, United States

Location

Site Reference ID/Investigator# 46028

Orangeburg, South Carolina, 29118, United States

Location

Site Reference ID/Investigator# 46702

Orangeburg, South Carolina, 29118, United States

Location

Site Reference ID/Investigator# 46024

Greenville, Texas, 75402, United States

Location

Site Reference ID/Investigator# 46228

Houston, Texas, 77004, United States

Location

Site Reference ID/Investigator# 47068

Houston, Texas, 77004, United States

Location

Site Reference ID/Investigator# 64464

Houston, Texas, 77054, United States

Location

Site Reference ID/Investigator# 64483

Mission, Texas, 78572, United States

Location

Site Reference ID/Investigator# 46348

San Antonio, Texas, 78215, United States

Location

Site Reference ID/Investigator# 46063

San Antonio, Texas, 78229-4801, United States

Location

Site Reference ID/Investigator# 68486

San Antonio, Texas, 78229, United States

Location

Site Reference ID/Investigator# 46669

Bennington, Vermont, 05201, United States

Location

Site Reference ID/Investigator# 46026

Alexandria, Virginia, 22304, United States

Location

Site Reference ID/Investigator# 46027

Fairfax, Virginia, 22030, United States

Location

Site Reference ID/Investigator# 67762

Kitchener, N2H 5Z8, Canada

Location

Site Reference ID/Investigator# 50526

Sarnia, N7T 4X3, Canada

Location

Site Reference ID/Investigator# 50525

Thornhill, L4J 8L7, Canada

Location

Site Reference ID/Investigator# 47067

Caguas, 00725, Puerto Rico

Location

Site Reference ID/Investigator# 50522

Manatí, 00674, Puerto Rico

Location

Site Reference ID/Investigator# 46352

Ponce, 00717-1322, Puerto Rico

Location

Site Reference ID/Investigator# 46351

Ponce, 00717-2075, Puerto Rico

Location

Site Reference ID/Investigator# 46133

Ponce, 00717, Puerto Rico

Location

Site Reference ID/Investigator# 46131

Rio Piedras, 00935, Puerto Rico

Location

Site Reference ID/Investigator# 46132

San Juan, 00918, Puerto Rico

Location

Site Reference ID/Investigator# 46230

Santurce, 00909-2244, Puerto Rico

Location

Site Reference ID/Investigator# 51566

Taichung, 40447, Taiwan

Location

Site Reference ID/Investigator# 51567

Taichung, 40705, Taiwan

Location

Related Publications (2)

• 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.

  PMID: 37716952 DERIVED

• 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.

  PMID: 28756065 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Diabetic Nephropathies; Proteinuria

Interventions

Atrasentan

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodioxoles; Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrrolidines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Blai Coll, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2011
• First Posted: May 20, 2011
• Study Start: April 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: August 28, 2013

Record last verified: 2013-08

Locations

US (59); TW (2); PR (8); CA (3)