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

NCT01399580 | Completed Phase 2

• 1 other identifier: M12-830
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 28

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.

Conditions

Chronic Kidney Disease; Diabetic Nephropathy

Keywords

endothelin receptor antagonists

Outcome Measures

Primary Outcomes (1)

• Change from baseline to each post-baseline visit up to Week 8 in log-transformed Urinary Albumin to Creatinine Ratio (UACR)

  Every two weeks for 8 weeks

Secondary Outcomes (2)

• Change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR)

  Every two weeks for 8 weeks

• The change from baseline to each post-baseline assessment of thoracic bioimpedance

  Treatment Day 1, Week 1, 2, 4, 6, 8 and 30 days post-treatment

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 8 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 8 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:

• Subject is greater than or equal to 18 years old.
• 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.
• Subject is currently receiving an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin II receptor blocker (ARB) (Renin Angiotensin System (RAS) inhibitor).
• 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.
• 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%
• 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)

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.
• 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.
• Subject has a history of pulmonary edema.
• Subject has a history of pulmonary hypertension, or any lung diseases requiring oxygen therapy (i.e., chronic obstructive pulmonary disease, emphysema, pulmonary fibrosis).
• 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (28)

Site Reference ID/Investigator# 58144

Phoenix, Arizona, 85032, United States

Location

Site Reference ID/Investigator# 71034

Tempe, Arizona, 85284, United States

Location

Site Reference ID/Investigator# 56927

Azusa, California, 91702, United States

Location

Site Reference ID/Investigator# 70793

Azusa, California, 91702, United States

Location

Site Reference ID/Investigator# 64027

Chula Vista, California, 91910, United States

Location

Site Reference ID/Investigator# 54120

Concord, California, 94520, United States

Location

Site Reference ID/Investigator# 64026

La Mesa, California, 91942, United States

Location

Site Reference ID/Investigator# 70173

Los Angeles, California, 90048, United States

Location

Site Reference ID/Investigator# 54121

Denver, Colorado, 80209, United States

Location

Site Reference ID/Investigator# 56924

Boynton Beach, Florida, 33472, United States

Location

Site Reference ID/Investigator# 56642

Hollywood, Florida, 33021, United States

Location

Site Reference ID/Investigator# 68986

Augusta, Georgia, 30901, United States

Location

Site Reference ID/Investigator# 56644

Chicago, Illinois, 60611, United States

Location

Site Reference ID/Investigator# 54129

Baton Rouge, Louisiana, 70808, United States

Location

Site Reference ID/Investigator# 68982

Pontiac, Michigan, 48341, United States

Location

Site Reference ID/Investigator# 64023

Albany, New York, 12206, United States

Location

Site Reference ID/Investigator# 55543

Flushing, New York, 11355, United States

Location

Site Reference ID/Investigator# 54164

Fargo, North Dakota, 58103, United States

Location

Site Reference ID/Investigator# 58147

Willoughby Hills, Ohio, 44094, United States

Location

Site Reference ID/Investigator# 54123

Bethlehem, Pennsylvania, 18017, United States

Location

Site Reference ID/Investigator# 61742

Pittsburgh, Pennsylvania, 15224, United States

Location

Site Reference ID/Investigator# 54132

Chattanooga, Tennessee, 37408, United States

Location

Site Reference ID/Investigator# 54108

Dallas, Texas, 75231, United States

Location

Site Reference ID/Investigator# 54126

Greenville, Texas, 75402, United States

Location

Site Reference ID/Investigator# 58153

Houston, Texas, 77024, United States

Location

Site Reference ID/Investigator# 54110

Houston, Texas, 77099, United States

Location

Site Reference ID/Investigator# 54116

North Richland Hills, Texas, 76180, United States

Location

Site Reference ID/Investigator# 54173

Silverdale, Washington, 98383, United States

Location

Related Publications (1)

• 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

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

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: July 20, 2011
• First Posted: July 22, 2011
• Study Start: August 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: October 25, 2013

Record last verified: 2013-09

Locations

US (28)