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RADAR: 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

Sponsor
AbbVie (prior sponsor, Abbott) (Industry)
Overall Status
Completed
CT.gov ID
NCT01356849
Collaborator
(none)
149
Enrollment
72
Locations
3
Arms
16
Duration (Months)
2.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
149 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Study Start Date :
Apr 1, 2011
Actual Primary Completion Date :
Aug 1, 2012
Actual Study Completion Date :
Aug 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Group A - Placebo QD

Drug: Placebo
Subjects will take two tablets daily of placebo QD for 12 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 12 weeks during the treatment period.
Other Names:
  • 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 12 weeks during the treatment period.
    Other Names:
  • ABT-627

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change from baseline to Week 12 in Urinary Albumin to Creatinine Ratio (UACR) [Every two weeks for 12 weeks]

    Secondary Outcome Measures

    1. Differences in change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR) [Every two weeks for 12 weeks]

    2. Differences in change from baseline to each post baseline measure for EQ-5D Index Score [Once a month for 3 months]

    3. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Site Reference ID/Investigator# 46345 Pell City Alabama United States 35128
    2 Site Reference ID/Investigator# 46035 Tempe Arizona United States 85284
    3 Site Reference ID/Investigator# 46016 Azusa California United States 91702
    4 Site Reference ID/Investigator# 45992 Chula Vista California United States 91910
    5 Site Reference ID/Investigator# 46000 La Mesa California United States 91942
    6 Site Reference ID/Investigator# 46038 Lincoln California United States 95648
    7 Site Reference ID/Investigator# 45994 Long Beach California United States 90806
    8 Site Reference ID/Investigator# 45998 Los Angeles California United States 90022
    9 Site Reference ID/Investigator# 47584 Los Gatos California United States 95032
    10 Site Reference ID/Investigator# 64465 National City California United States 91950
    11 Site Reference ID/Investigator# 65862 Orange California United States 92868
    12 Site Reference ID/Investigator# 46019 Riverside California United States 92505
    13 Site Reference ID/Investigator# 46110 Salinas California United States 93901
    14 Site Reference ID/Investigator# 46017 Yuba City California United States 95991
    15 Site Reference ID/Investigator# 46662 Westminster Colorado United States 80031
    16 Site Reference ID/Investigator# 46033 Coral Gables Florida United States 33134
    17 Site Reference ID/Investigator# 45989 Hialeah Florida United States 33012
    18 Site Reference ID/Investigator# 46667 Lauderdale Lakes Florida United States 33313
    19 Site Reference ID/Investigator# 46123 Miami Florida United States 33135
    20 Site Reference ID/Investigator# 46115 Ocala Florida United States 34471
    21 Site Reference ID/Investigator# 46664 Pembroke Pines Florida United States 33027
    22 Site Reference ID/Investigator# 46031 Pembroke Pines Florida United States 33028
    23 Site Reference ID/Investigator# 46040 Pembroke Pines Florida United States 33028
    24 Site Reference ID/Investigator# 46122 Port Charlotte Florida United States 33952
    25 Site Reference ID/Investigator# 46015 West Palm Beach Florida United States 33401
    26 Site Reference ID/Investigator# 50482 Jonesboro Georgia United States 30236
    27 Site Reference ID/Investigator# 46034 Meridian Idaho United States 83642
    28 Site Reference ID/Investigator# 46666 Chicago Illinois United States 60616
    29 Site Reference ID/Investigator# 45996 Evergreen Park Illinois United States 60805
    30 Site Reference ID/Investigator# 46002 Gurnee Illinois United States 60031
    31 Site Reference ID/Investigator# 46111 Shreveport Louisiana United States 71101
    32 Site Reference ID/Investigator# 46030 Oxon Hill Maryland United States 20745
    33 Site Reference ID/Investigator# 45991 Rockville Maryland United States 20852
    34 Site Reference ID/Investigator# 46025 Novi Michigan United States 48374
    35 Site Reference ID/Investigator# 46023 Brooklyn Center Minnesota United States 55430
    36 Site Reference ID/Investigator# 46062 Farmington Missouri United States 63640
    37 Site Reference ID/Investigator# 48942 Omaha Nebraska United States 68131-3403
    38 Site Reference ID/Investigator# 46349 Omaha Nebraska United States 68131
    39 Site Reference ID/Investigator# 46116 Las Vegas Nevada United States 89106
    40 Site Reference ID/Investigator# 50483 Albany New York United States 12206
    41 Site Reference ID/Investigator# 68328 New Hyde Park New York United States 11042
    42 Site Reference ID/Investigator# 65863 Asheville North Carolina United States 28801
    43 Site Reference ID/Investigator# 50529 Greensboro North Carolina United States 27408
    44 Site Reference ID/Investigator# 46129 Greenville North Carolina United States 27834
    45 Site Reference ID/Investigator# 46022 Morehead City North Carolina United States 28557
    46 Site Reference ID/Investigator# 46224 Doylestown Pennsylvania United States 18901
    47 Site Reference ID/Investigator# 46028 Orangeburg South Carolina United States 29118
    48 Site Reference ID/Investigator# 46702 Orangeburg South Carolina United States 29118
    49 Site Reference ID/Investigator# 46024 Greenville Texas United States 75402
    50 Site Reference ID/Investigator# 46228 Houston Texas United States 77004
    51 Site Reference ID/Investigator# 47068 Houston Texas United States 77004
    52 Site Reference ID/Investigator# 64464 Houston Texas United States 77054
    53 Site Reference ID/Investigator# 64483 Mission Texas United States 78572
    54 Site Reference ID/Investigator# 46348 San Antonio Texas United States 78215
    55 Site Reference ID/Investigator# 46063 San Antonio Texas United States 78229-4801
    56 Site Reference ID/Investigator# 68486 San Antonio Texas United States 78229
    57 Site Reference ID/Investigator# 46669 Bennington Vermont United States 05201
    58 Site Reference ID/Investigator# 46026 Alexandria Virginia United States 22304
    59 Site Reference ID/Investigator# 46027 Fairfax Virginia United States 22030
    60 Site Reference ID/Investigator# 67762 Kitchener Canada N2H 5Z8
    61 Site Reference ID/Investigator# 50526 Sarnia Canada N7T 4X3
    62 Site Reference ID/Investigator# 50525 Thornhill Canada L4J 8L7
    63 Site Reference ID/Investigator# 47067 Caguas Puerto Rico 00725
    64 Site Reference ID/Investigator# 50522 Manati Puerto Rico 00674
    65 Site Reference ID/Investigator# 46352 Ponce Puerto Rico 00717-1322
    66 Site Reference ID/Investigator# 46351 Ponce Puerto Rico 00717-2075
    67 Site Reference ID/Investigator# 46133 Ponce Puerto Rico 00717
    68 Site Reference ID/Investigator# 46131 Rio Piedras Puerto Rico 00935
    69 Site Reference ID/Investigator# 46132 San Juan Puerto Rico 00918
    70 Site Reference ID/Investigator# 46230 Santurce Puerto Rico 00909-2244
    71 Site Reference ID/Investigator# 51566 Taichung City Taiwan 40447
    72 Site Reference ID/Investigator# 51567 Taichung Taiwan 40705

    Sponsors and Collaborators

    • AbbVie (prior sponsor, Abbott)

    Investigators

    • Study Director: Blai Coll, MD, AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AbbVie (prior sponsor, Abbott)
    ClinicalTrials.gov Identifier:
    NCT01356849
    Other Study ID Numbers:
    • M11-350
    First Posted:
    May 20, 2011
    Last Update Posted:
    Aug 28, 2013
    Last Verified:
    Aug 1, 2013
    Keywords provided by AbbVie (prior sponsor, Abbott)
    Endothelin Receptor Antagonists
    Proteinuria
    Additional relevant MeSH terms:
    Kidney Diseases
    Renal Insufficiency, Chronic
    Diabetic Nephropathies
    Albuminuria
    Atrasentan

    Study Results

    No Results Posted as of Aug 28, 2013