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

Chronic Kidney Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01399580
• Other study ID #: M12-830
• Status: Completed
• Phase: Phase 2
• First received: July 20, 2011
• Last updated: September 25, 2013
• Start date: August 2011
• Est. completion date: September 2012

Study information

• Verified date: September 2013
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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

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

Locations

Country	Name	City	State
United States	Site Reference ID/Investigator# 64023	Albany	New York
United States	Site Reference ID/Investigator# 68986	Augusta	Georgia
United States	Site Reference ID/Investigator# 56927	Azusa	California
United States	Site Reference ID/Investigator# 70793	Azusa	California
United States	Site Reference ID/Investigator# 54129	Baton Rouge	Louisiana
United States	Site Reference ID/Investigator# 54123	Bethlehem	Pennsylvania
United States	Site Reference ID/Investigator# 56924	Boynton Beach	Florida
United States	Site Reference ID/Investigator# 54132	Chattanooga	Tennessee
United States	Site Reference ID/Investigator# 56644	Chicago	Illinois
United States	Site Reference ID/Investigator# 64027	Chula Vista	California
United States	Site Reference ID/Investigator# 54120	Concord	California
United States	Site Reference ID/Investigator# 54108	Dallas	Texas
United States	Site Reference ID/Investigator# 54121	Denver	Colorado
United States	Site Reference ID/Investigator# 54164	Fargo	North Dakota
United States	Site Reference ID/Investigator# 55543	Flushing	New York
United States	Site Reference ID/Investigator# 54126	Greenville	Texas
United States	Site Reference ID/Investigator# 56642	Hollywood	Florida
United States	Site Reference ID/Investigator# 54110	Houston	Texas
United States	Site Reference ID/Investigator# 58153	Houston	Texas
United States	Site Reference ID/Investigator# 64026	La Mesa	California
United States	Site Reference ID/Investigator# 70173	Los Angeles	California
United States	Site Reference ID/Investigator# 54116	North Richland Hills	Texas
United States	Site Reference ID/Investigator# 58144	Phoenix	Arizona
United States	Site Reference ID/Investigator# 61742	Pittsburg	Pennsylvania
United States	Site Reference ID/Investigator# 68982	Pontiac	Michigan
United States	Site Reference ID/Investigator# 54173	Silverdale	Washington
United States	Site Reference ID/Investigator# 71034	Tempe	Arizona
United States	Site Reference ID/Investigator# 58147	Willoughby Hills	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to each post-baseline visit up to Week 8 in log-transformed Urinary Albumin to Creatinine Ratio (UACR)		Every two weeks for 8 weeks	No
Secondary	Change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR)		Every two weeks for 8 weeks	No
Secondary	The change from baseline to each post-baseline assessment of thoracic bioimpedance		Treatment Day 1, Week 1, 2, 4, 6, 8 and 30 days post-treatment	Yes