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

Chronic Kidney Disease Clinical Trial

— RADAR  

Official title:

RADAR: Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan - A Phase 2b, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety and Efficacy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01356849
• Other study ID #: M11-350
• Status: Completed
• Phase: Phase 2
• First received: April 19, 2011
• Last updated: August 20, 2013
• Start date: April 2011
• Est. completion date: August 2012

Study information

• Verified date: August 2013
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of HealthCanada: Health CanadaUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 149
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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)

• Negative serum pregnancy test for female patients

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Albuminuria
• Chronic Kidney Disease
• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Atrasentan
Subjects will take two tablets daily of either low dose Atrasentan QD or high dose Atrasentan QD for 12 weeks during the treatment period.
• Placebo
Subjects will take two tablets daily of placebo QD for 12 weeks during the treatment period.

Locations

Country	Name	City	State
Canada	Site Reference ID/Investigator# 67762	Kitchener
Canada	Site Reference ID/Investigator# 50526	Sarnia
Canada	Site Reference ID/Investigator# 50525	Thornhill
Puerto Rico	Site Reference ID/Investigator# 47067	Caguas
Puerto Rico	Site Reference ID/Investigator# 50522	Manati
Puerto Rico	Site Reference ID/Investigator# 46133	Ponce
Puerto Rico	Site Reference ID/Investigator# 46351	Ponce
Puerto Rico	Site Reference ID/Investigator# 46352	Ponce
Puerto Rico	Site Reference ID/Investigator# 46131	Rio Piedras
Puerto Rico	Site Reference ID/Investigator# 46132	San Juan
Puerto Rico	Site Reference ID/Investigator# 46230	Santurce
Taiwan	Site Reference ID/Investigator# 51567	Taichung
Taiwan	Site Reference ID/Investigator# 51566	Taichung City
United States	Site Reference ID/Investigator# 50483	Albany	New York
United States	Site Reference ID/Investigator# 46026	Alexandria	Virginia
United States	Site Reference ID/Investigator# 65863	Asheville	North Carolina
United States	Site Reference ID/Investigator# 46016	Azusa	California
United States	Site Reference ID/Investigator# 46669	Bennington	Vermont
United States	Site Reference ID/Investigator# 46023	Brooklyn Center	Minnesota
United States	Site Reference ID/Investigator# 46666	Chicago	Illinois
United States	Site Reference ID/Investigator# 45992	Chula Vista	California
United States	Site Reference ID/Investigator# 46033	Coral Gables	Florida
United States	Site Reference ID/Investigator# 46224	Doylestown	Pennsylvania
United States	Site Reference ID/Investigator# 45996	Evergreen Park	Illinois
United States	Site Reference ID/Investigator# 46027	Fairfax	Virginia
United States	Site Reference ID/Investigator# 46062	Farmington	Missouri
United States	Site Reference ID/Investigator# 50529	Greensboro	North Carolina
United States	Site Reference ID/Investigator# 46024	Greenville	Texas
United States	Site Reference ID/Investigator# 46129	Greenville	North Carolina
United States	Site Reference ID/Investigator# 46002	Gurnee	Illinois
United States	Site Reference ID/Investigator# 45989	Hialeah	Florida
United States	Site Reference ID/Investigator# 46228	Houston	Texas
United States	Site Reference ID/Investigator# 47068	Houston	Texas
United States	Site Reference ID/Investigator# 64464	Houston	Texas
United States	Site Reference ID/Investigator# 50482	Jonesboro	Georgia
United States	Site Reference ID/Investigator# 46000	La Mesa	California
United States	Site Reference ID/Investigator# 46116	Las Vegas	Nevada
United States	Site Reference ID/Investigator# 46667	Lauderdale Lakes	Florida
United States	Site Reference ID/Investigator# 46038	Lincoln	California
United States	Site Reference ID/Investigator# 45994	Long Beach	California
United States	Site Reference ID/Investigator# 45998	Los Angeles	California
United States	Site Reference ID/Investigator# 47584	Los Gatos	California
United States	Site Reference ID/Investigator# 46034	Meridian	Idaho
United States	Site Reference ID/Investigator# 46123	Miami	Florida
United States	Site Reference ID/Investigator# 64483	Mission	Texas
United States	Site Reference ID/Investigator# 46022	Morehead City	North Carolina
United States	Site Reference ID/Investigator# 64465	National City	California
United States	Site Reference ID/Investigator# 68328	New Hyde Park	New York
United States	Site Reference ID/Investigator# 46025	Novi	Michigan
United States	Site Reference ID/Investigator# 46115	Ocala	Florida
United States	Site Reference ID/Investigator# 46349	Omaha	Nebraska
United States	Site Reference ID/Investigator# 48942	Omaha	Nebraska
United States	Site Reference ID/Investigator# 65862	Orange	California
United States	Site Reference ID/Investigator# 46028	Orangeburg	South Carolina
United States	Site Reference ID/Investigator# 46702	Orangeburg	South Carolina
United States	Site Reference ID/Investigator# 46030	Oxon Hill	Maryland
United States	Site Reference ID/Investigator# 46345	Pell City	Alabama
United States	Site Reference ID/Investigator# 46031	Pembroke Pines	Florida
United States	Site Reference ID/Investigator# 46040	Pembroke Pines	Florida
United States	Site Reference ID/Investigator# 46664	Pembroke Pines	Florida
United States	Site Reference ID/Investigator# 46122	Port Charlotte	Florida
United States	Site Reference ID/Investigator# 46019	Riverside	California
United States	Site Reference ID/Investigator# 45991	Rockville	Maryland
United States	Site Reference ID/Investigator# 46110	Salinas	California
United States	Site Reference ID/Investigator# 46063	San Antonio	Texas
United States	Site Reference ID/Investigator# 46348	San Antonio	Texas
United States	Site Reference ID/Investigator# 68486	San Antonio	Texas
United States	Site Reference ID/Investigator# 46111	Shreveport	Louisiana
United States	Site Reference ID/Investigator# 46035	Tempe	Arizona
United States	Site Reference ID/Investigator# 46015	West Palm Beach	Florida
United States	Site Reference ID/Investigator# 46662	Westminster	Colorado
United States	Site Reference ID/Investigator# 46017	Yuba City	California

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to Week 12 in Urinary Albumin to Creatinine Ratio (UACR)		Every two weeks for 12 weeks	No
Secondary	Differences in change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR)		Every two weeks for 12 weeks	No
Secondary	Differences in change from baseline to each post baseline measure for EQ-5D Index Score		Once a month for 3 months	No
Secondary	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	No