Clinical trial NCT01399580: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Diabetic Nephropathy
Keywords: endothelin receptor antagonists
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2011-07-22
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change from baseline to each post-baseline visit up to Week 8 in log-transformed Urinary Albumin to Creatinine Ratio (UACR)
timeFrame: Every two weeks for 8 weeks
Secondary outcomes:
measure: Change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR)
timeFrame: Every two weeks for 8 weeks
measure: The change from baseline to each post-baseline assessment of thoracic bioimpedance
timeFrame: Treatment Day 1, Week 1, 2, 4, 6, 8 and 30 days post-treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Site Reference ID/Investigator# 58144
state: Arizona
city: Tempe
country: United States
facility: Site Reference ID/Investigator# 71034
state: Arizona
city: Azusa
country: United States
facility: Site Reference ID/Investigator# 56927
state: California
city: Azusa
country: United States
facility: Site Reference ID/Investigator# 70793
state: California
city: Chula Vista
country: United States
facility: Site Reference ID/Investigator# 64027
state: California
city: Concord
country: United States
facility: Site Reference ID/Investigator# 54120
state: California
city: La Mesa
country: United States
facility: Site Reference ID/Investigator# 64026
state: California
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator# 70173
state: California
city: Denver
country: United States
facility: Site Reference ID/Investigator# 54121
state: Colorado
city: Boynton Beach
country: United States
facility: Site Reference ID/Investigator# 56924
state: Florida
city: Hollywood
country: United States
facility: Site Reference ID/Investigator# 56642
state: Florida
city: Augusta
country: United States
facility: Site Reference ID/Investigator# 68986
state: Georgia
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 56644
state: Illinois
city: Baton Rouge
country: United States
facility: Site Reference ID/Investigator# 54129
state: Louisiana
city: Pontiac
country: United States
facility: Site Reference ID/Investigator# 68982
state: Michigan
city: Albany
country: United States
facility: Site Reference ID/Investigator# 64023
state: New York
city: Flushing
country: United States
facility: Site Reference ID/Investigator# 55543
state: New York
city: Fargo
country: United States
facility: Site Reference ID/Investigator# 54164
state: North Dakota
city: Willoughby Hills
country: United States
facility: Site Reference ID/Investigator# 58147
state: Ohio
city: Bethlehem
country: United States
facility: Site Reference ID/Investigator# 54123
state: Pennsylvania
city: Pittsburg
country: United States
facility: Site Reference ID/Investigator# 61742
state: Pennsylvania
city: Chattanooga
country: United States
facility: Site Reference ID/Investigator# 54132
state: Tennessee
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 54108
state: Texas
city: Greenville
country: United States
facility: Site Reference ID/Investigator# 54126
state: Texas
city: Houston
country: United States
facility: Site Reference ID/Investigator# 58153
state: Texas
city: Houston
country: United States
facility: Site Reference ID/Investigator# 54110
state: Texas
city: North Richland Hills
country: United States
facility: Site Reference ID/Investigator# 54116
state: Texas
city: Silverdale
country: United States
facility: Site Reference ID/Investigator# 54173
state: Washington
Study officials:
affiliation: AbbVie
name: Blai Coll, MD
role: STUDY_DIRECTOR
References:
citation: 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.