A Prospective, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate Efficacy and Safety of Atrasentan, Including Thoracic Bioimpedance, in Type 2 Diabetic Subjects With Nephropathy

Study Description

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Brief Summary:

Prospective, Randomized, Double-Blind, Parallel Design, Placebo-Controlled Multicenter Study. The study objectives are to evaluate efficacy and safety, including thoracic bioimpedance, of once daily administration of atrasentan tablets (high dose and low dose) compared to placebo in type 2 diabetic subjects with nephropathy who are receiving the maximum tolerated labeled daily dose of a RAS inhibitor.

Condition or disease	Intervention/treatment	Phase
Chronic Kidney Disease; Diabetic Nephropathy	Drug: Atrasentan; Drug: Placebo	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	48 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Phase 2b, Prospective, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate Efficacy and Safety of Atrasentan, Including Thoracic Bioimpedance, in Type 2 Diabetic Subjects With Nephropathy
Study Start Date :	August 2011
Actual Primary Completion Date :	September 2012
Actual Study Completion Date :	September 2012

Arms and Interventions

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Arm	Intervention/treatment
Placebo Comparator: Group A - Placebo QD	Drug: Placebo; Subjects will take two tablets daily of placebo QD for 8 weeks during the treatment period.
Active Comparator: Group B - Low dose Atrasentan QD	Drug: Atrasentan; Subjects will take two tablets daily of either low dose Atrasentan QD or high dose Atrasentan QD for 8 weeks during the treatment period.; Other Name: ABT-627
Active Comparator: Group C - High dose Atrasentan QD	Drug: Atrasentan; Subjects will take two tablets daily of either low dose Atrasentan QD or high dose Atrasentan QD for 8 weeks during the treatment period.; Other Name: ABT-627

Outcome Measures

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Primary Outcome Measures :

1. Change from baseline to each post-baseline visit up to Week 8 in log-transformed Urinary Albumin to Creatinine Ratio (UACR) [ Time Frame: Every two weeks for 8 weeks ]

Secondary Outcome Measures :

1. Change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR) [ Time Frame: Every two weeks for 8 weeks ]
2. The change from baseline to each post-baseline assessment of thoracic bioimpedance [ Time Frame: Treatment Day 1, Week 1, 2, 4, 6, 8 and 30 days post-treatment ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Subject is greater than or equal to 18 years old.
2. Subject has type 2 diabetes and has been treated with at least one anti-hyperglycemic medication within the 12 months prior to the Screening Period.
3. Subject is currently receiving an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin II receptor blocker (ARB) (Renin Angiotensin System (RAS) inhibitor).
4. If female, subject is not breastfeeding and is not pregnant (verified by negative serum pregnancy test prior to the Treatment Period). Subject is not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or is of childbearing potential and practicing one of the approved methods of birth control as defined in the Clinical Trial Protocol. Contraception must be used during the study and for 4 weeks after the last dose of study drug.

5. For entry into the Run-in Period the subject must satisfy the following criteria based on the Screening laboratory values:

   • Estimated glomerular filtration rate (eGFR) greater than or equal to 30 and less than or equal to 75 mL/min/1.73m^2 by the Epidemiology Collaboration (EPI) formula
   • Urinary Albumin to Creatinine Ratio (UACR) greater than or equal to 300 and less than or equal to 3500 mg/g as determined by the geometric mean of the two morning void urine specimens obtained at the Screening visit
   • Serum albumin greater than or equal to 3.0 g/dL
   • B-Type Natriuretic Peptide (BNP) less than or equal to 200 pg/mL
   • Negative serum pregnancy test for female subjects
   • Systolic Blood Pressure (SBP) greater than or equal to 110 mmHg and less than or equal to 180 mmHg
   • Glucosylated hemoglobin (HbA1c) less than or equal to 12%

6. For entry into the Treatment Period the subject 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 adjustment of dose
   • Diuretic at any dose unless medically contraindicated (with the exception of loop diuretics greater than or equal to 120 mg QD of furosemide or greater than or equal to 3.0 mg QD of bumetanide or greater than or equal to 150 mg QD of ethacrynic acid or greater than or equal to 60 mg QD of torasemide)
   • UACR ≥ 200 mg/g as determined by the median of the three morning void urine specimens obtained prior to the Week -1 visit
   • Systolic Blood Pressure (SBP) greater than or equal to 110 mmHg and less than or equal to 160 mmHg
   • Serum Potassium less than or equal to 5.5 mEq/L
   • Negative serum pregnancy test for female subjects

Exclusion Criteria:

1. 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.
2. Subject is receiving loop diuretics greater than or equal to 120 mg QD of furosemide or greater than or equal to 3.0 mg QD of bumetanide or greater than or equal to 150 mg QD of ethacrynic acid or greater than or equal to 60 mg QD of torasemide.
3. Subject has a history of pulmonary edema.
4. Subject has a history of pulmonary hypertension, or any lung diseases requiring oxygen therapy (i.e., chronic obstructive pulmonary disease, emphysema, pulmonary fibrosis).
5. Subject has a history of orthostatic hypotension within the past 6 months as defined by the presence of a supine-to-standing blood pressure decrease greater than or equal to 20 mmHg systolic or greater than or equal to 10 mmHg diastolic within 3 minutes of standing.

Contacts and Locations

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Locations

United States, Arizona
Site Reference ID/Investigator# 58144
Phoenix, Arizona, United States, 85032
Site Reference ID/Investigator# 71034
Tempe, Arizona, United States, 85284
United States, California
Site Reference ID/Investigator# 56927
Azusa, California, United States, 91702
Site Reference ID/Investigator# 70793
Azusa, California, United States, 91702
Site Reference ID/Investigator# 64027
Chula Vista, California, United States, 91910
Site Reference ID/Investigator# 54120
Concord, California, United States, 94520
Site Reference ID/Investigator# 64026
La Mesa, California, United States, 91942
Site Reference ID/Investigator# 70173
Los Angeles, California, United States, 90048
United States, Colorado
Site Reference ID/Investigator# 54121
Denver, Colorado, United States, 80209
United States, Florida
Site Reference ID/Investigator# 56924
Boynton Beach, Florida, United States, 33472
Site Reference ID/Investigator# 56642
Hollywood, Florida, United States, 33021
United States, Georgia
Site Reference ID/Investigator# 68986
Augusta, Georgia, United States, 30901
United States, Illinois
Site Reference ID/Investigator# 56644
Chicago, Illinois, United States, 60611
United States, Louisiana
Site Reference ID/Investigator# 54129
Baton Rouge, Louisiana, United States, 70808
United States, Michigan
Site Reference ID/Investigator# 68982
Pontiac, Michigan, United States, 48341
United States, New York
Site Reference ID/Investigator# 64023
Albany, New York, United States, 12206
Site Reference ID/Investigator# 55543
Flushing, New York, United States, 11355
United States, North Dakota
Site Reference ID/Investigator# 54164
Fargo, North Dakota, United States, 58103
United States, Ohio
Site Reference ID/Investigator# 58147
Willoughby Hills, Ohio, United States, 44094
United States, Pennsylvania
Site Reference ID/Investigator# 54123
Bethlehem, Pennsylvania, United States, 18017
Site Reference ID/Investigator# 61742
Pittsburg, Pennsylvania, United States, 15224
United States, Tennessee
Site Reference ID/Investigator# 54132
Chattanooga, Tennessee, United States, 37408
United States, Texas
Site Reference ID/Investigator# 54108
Dallas, Texas, United States, 75231
Site Reference ID/Investigator# 54126
Greenville, Texas, United States, 75402
Site Reference ID/Investigator# 58153
Houston, Texas, United States, 77024
Site Reference ID/Investigator# 54110
Houston, Texas, United States, 77099
Site Reference ID/Investigator# 54116
North Richland Hills, Texas, United States, 76180
United States, Washington
Site Reference ID/Investigator# 54173
Silverdale, Washington, United States, 98383

Sponsors and Collaborators

AbbVie (prior sponsor, Abbott)

Investigators

Study Director:	Blai Coll, MD	AbbVie

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	AbbVie (prior sponsor, Abbott)
ClinicalTrials.gov Identifier:	NCT01399580 History of Changes
Other Study ID Numbers:	M12-830
First Posted:	July 22, 2011
Last Update Posted:	October 25, 2013
Last Verified:	September 2013

Keywords provided by AbbVie ( AbbVie (prior sponsor, Abbott) ):

endothelin receptor antagonists

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Diabetic Nephropathies; Urologic Diseases; Renal Insufficiency; Diabetes Complications	Diabetes Mellitus; Endocrine System Diseases; Atrasentan; Endothelin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action