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

NCT ID: NCT01399580

Last Updated: 2013-10-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2012-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Kidney Disease Diabetic Nephropathy

Keywords

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endothelin receptor antagonists

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group A - Placebo QD

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Subjects will take two tablets daily of placebo QD for 8 weeks during the treatment period.

Group B - Low dose Atrasentan QD

Group Type ACTIVE_COMPARATOR

Atrasentan

Intervention Type 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.

Group C - High dose Atrasentan QD

Group Type ACTIVE_COMPARATOR

Atrasentan

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Placebo

Subjects will take two tablets daily of placebo QD for 8 weeks during the treatment period.

Intervention Type DRUG

Other Intervention Names

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ABT-627

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Blai Coll, MD

Role: STUDY_DIRECTOR

AbbVie

Locations

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Site Reference ID/Investigator# 58144

Phoenix, Arizona, United States

Site Status

Site Reference ID/Investigator# 71034

Tempe, Arizona, United States

Site Status

Site Reference ID/Investigator# 56927

Azusa, California, United States

Site Status

Site Reference ID/Investigator# 70793

Azusa, California, United States

Site Status

Site Reference ID/Investigator# 64027

Chula Vista, California, United States

Site Status

Site Reference ID/Investigator# 54120

Concord, California, United States

Site Status

Site Reference ID/Investigator# 64026

La Mesa, California, United States

Site Status

Site Reference ID/Investigator# 70173

Los Angeles, California, United States

Site Status

Site Reference ID/Investigator# 54121

Denver, Colorado, United States

Site Status

Site Reference ID/Investigator# 56924

Boynton Beach, Florida, United States

Site Status

Site Reference ID/Investigator# 56642

Hollywood, Florida, United States

Site Status

Site Reference ID/Investigator# 68986

Augusta, Georgia, United States

Site Status

Site Reference ID/Investigator# 56644

Chicago, Illinois, United States

Site Status

Site Reference ID/Investigator# 54129

Baton Rouge, Louisiana, United States

Site Status

Site Reference ID/Investigator# 68982

Pontiac, Michigan, United States

Site Status

Site Reference ID/Investigator# 64023

Albany, New York, United States

Site Status

Site Reference ID/Investigator# 55543

Flushing, New York, United States

Site Status

Site Reference ID/Investigator# 54164

Fargo, North Dakota, United States

Site Status

Site Reference ID/Investigator# 58147

Willoughby Hills, Ohio, United States

Site Status

Site Reference ID/Investigator# 54123

Bethlehem, Pennsylvania, United States

Site Status

Site Reference ID/Investigator# 61742

Pittsburgh, Pennsylvania, United States

Site Status

Site Reference ID/Investigator# 54132

Chattanooga, Tennessee, United States

Site Status

Site Reference ID/Investigator# 54108

Dallas, Texas, United States

Site Status

Site Reference ID/Investigator# 54126

Greenville, Texas, United States

Site Status

Site Reference ID/Investigator# 58153

Houston, Texas, United States

Site Status

Site Reference ID/Investigator# 54110

Houston, Texas, United States

Site Status

Site Reference ID/Investigator# 54116

North Richland Hills, Texas, United States

Site Status

Site Reference ID/Investigator# 54173

Silverdale, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 28756065 (View on PubMed)

Other Identifiers

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M12-830

Identifier Type: -

Identifier Source: org_study_id