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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01399580
First received: July 20, 2011
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Chronic Kidney Disease
Diabetic Nephropathy
Drug: Atrasentan
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Change from baseline to each post-baseline visit up to Week 8 in log-transformed Urinary Albumin to Creatinine Ratio (UACR) [ Time Frame: Every two weeks for 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR) [ Time Frame: Every two weeks for 8 weeks ] [ Designated as safety issue: No ]
  • The change from baseline to each post-baseline assessment of thoracic bioimpedance [ Time Frame: Treatment Day 1, Week 1, 2, 4, 6, 8 and 30 days post-treatment ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: August 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Group A - Placebo QD Drug: Placebo
Subjects will take two tablets daily of placebo QD for 8 weeks during the treatment period.
Other Name: Placebo
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 8 weeks during the treatment period.
Other Name: 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 8 weeks during the treatment period.
Other Name: ABT-627

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01399580

  Show 28 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Blai Coll, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01399580     History of Changes
Other Study ID Numbers: M12-830
Study First Received: July 20, 2011
Last Updated: September 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
endothelin receptor antagonists

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Renal Insufficiency, Chronic
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Renal Insufficiency
Urologic Diseases

ClinicalTrials.gov processed this record on November 20, 2014