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

• Register: ClinicalTrials.gov
• Last refreshed on: 7 January 2013
• Main ID: NCT01399580
• Date of registration: 20/07/2011
• Primary sponsor: AbbVie (prior sponsor, Abbott)
• Public title: 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
• Scientific 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
• Date of first enrolment: August 2011
• Target sample size: 48
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01399580
• 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

Countries of recruitment

United States

Contacts

• Name: Blai Coll, MD
• Affiliation: AbbVie

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic Kidney Disease

Diabetic Nephropathy

Intervention(s)

Drug: Atrasentan

Drug: Placebo

Primary Outcome(s)

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]

Secondary Outcome(s)

Change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR) [Time Frame: Every two weeks for 8 weeks]

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]

Secondary ID(s)

M12-830

Source(s) of Monetary Support

Please refer to primary and secondary sponsors