A Study of the Effects of Atrasentan (ABT-627) on Renal Outcomes in Subjects with Type 2 Diabetes and Nephropathy

Phase 1

• Conditions: Diabetic Nephropathy; MedDRA version: 18.0 Level: PT Classification code 10061835 Term: Diabetic nephropathy System Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2012-005848-21-NL
• Lead Sponsor: AbbVie Deutschland GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-09-25
• Study Completion: 2018-03-29
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 5107

Inclusion Criteria

1. Subject has type 2 diabetes (including patients with latent autoimmune diabetes or insulin-treated patients without a history of diabetic ketoacidosis who also have a negative anti-glutamic acid decarboxylase test AND an elevated post-prandial serum C-peptide level) and has been treated with at least one anti-hyperglycemic medication and ACEi/or ARB (RAS inhibitor) for at least 4 weeks prior to the Screening S2 visit.
2. For entry into the Run-In Period, the subject must satisfy the following criteria:
Screening laboratory values:
? Estimated GFR 25 to 75 mL/min/1.73 m2 and a UACR = 300 and
< 5,000 mg/g (= 34 mg/mmol and < 565 mg/mmol);
? Serum albumin = 2.5 g/dL (25 g/L);
? BNP = 200 pg/mL (200 ng/L);
? Serum Potassium = 3.5 mEq/L (3.5 mmol/L) = 6.0 mEq/L (6.0 mmol/L); and
? SBP = 110 and = 180 mmHg at any time during the Screening Period.
Subjects on a MTLDD of a RAS inhibitor for = 4 weeks and on a diuretic at the time of screening, and who satisfy the above criteria may proceed directly to the last visit in the Run-In Period (R6 visit).
Subjects on a MTLDD RAS inhibitor for = 4 weeks and not on a diuretic (unless medically contra-indicated) at the time of Screening will start with a diuretic and participate in Run-In for at least 2 weeks.
3. For entry into the Enrichment Period, the subject must satisfy the following criteria:
Based on the last visit of the Run-In Period:
? Subject received a RAS inhibitor at the MTLDD for the previous 4 weeks with no adjustments of the dose;
? Subject was on a MTLDD RAS inhibitor and not on a diuretic (unless
medically contra-indicated) at the time of Screening and has been in Run-In for at least 2 weeks.
For entry into the Double-Blind Treatment Period, the subject must satisfy the
following criteria:
7. Based on his/her last visit of the Enrichment Period:
? Subject has taken a RAS inhibitor at the MTLDD for the previous 6 weeks during the Enrichment Period with no adjustments of the dose;
? Subject has taken a diuretic at any dose unless medically contraindicated or clinically intolerable in the investigator's judgment (i.e., hypotension or hypokalemia);
? Subject must not have a weight change = 3 kg from the beginning of
Enrichment (E1) to the end of the Enrichment Period AND absolute serum BNP = 300 pg/mL (300 ng/L) at the last Enrichment visit;
? Subject must not have an increase in serum creatinine > 0.5 mg/dL
(> 48 umol/L) AND > 20% increase from the beginning of Enrichment (E1) to the end of the Enrichment Period
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4700

Exclusion Criteria

• Subject has a history of severe peripheral edema or facial edema
requiring diuretics unrelated to trauma or a history of myxedema in the
prior 4 weeks to the initial Screening S1 visit.
• Subject has a history of pulmonary hypertension, pulmonary fibrosis or
any lung disease requiring oxygen therapy (e.g., chronic obstructive
pulmonary disease, emphysema).
• Subject has a documented diagnosis of heart failure, previous
hospitalization for heart failure or current or constellation of symptoms
(dyspnea on exertion, pedal edema, orthopnea, paroxysmal nocturnal
dyspnea) felt to be compatible with heart failure, that was not explained by other causes, and for which there was a change in medication or other management directed at heart failure.
• Subject has known non-diabetic kidney disease (other than kidney
stones).
• Subject has elevated liver enzymes (serum alanine aminotransaminase [ALT] and/or serum aspartate aminotransaminase [AST]) > 3 × the upper limit of normal (ULN).
• Subject is currently receiving rosiglitazone, moxonidine, aldosterone
blockers, aliskiren, or a combination of ACEi and ARB.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified