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: 14.1Level: PTClassification code 10061835Term: Diabetic nephropathySystem Organ Class: 10038359 - Renal and urinary disorders
Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Registration Number: EUCTR2012-005848-21-ES

Lead Sponsor: AbbVie Deutschland GmbH & Co. KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 6200

Inclusion Criteria

1. Subject has type 2 diabetes and has been treated with at least one anti-hyperglycemic medication and ACEi/or ARB (RAS inhibitor) for at least 3 months prior to the Screening Period.
2. HbA1c ? 12%.
3. For entry into the Run-In Period the subject must satisfy the following criteria based on the Screening laboratory values:
? Estimated GFR 25 to 75 mL/min/1.73 m2 and a UACR ? 300 and < 5,000 mg/g (The number of subjects with eGFR between 60 to 75 mL/min/1.73 m2 will be capped to 10% of the total population);
? Serum albumin ? 3.0 g/dL (30 g/L);
? BNP ? 200 pg/mL (200 ng/L);
? SBP > 110 and <160 mmHg;
? Serum Potassium > 3.5 (3.5 mmol/L) and ? 5.5 mEq/L (5.5 mmol/L);
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 to the last visit in Run-In Period (R6);
Subjects already on a MTLDD of a RAS inhibitor for ? 4 weeks and not on a diuretic (unless medically contraindicated) at the time of Screening will start with a diuretic and proceed to Run-In for at least 2 weeks.
4. For entry into the Enrichment Period the subject must satisfy the following criteria based on the last visit of the Run-In Period:
? RAS inhibitor at the MTLDD for the previous 4 weeks with no adjustments of the dose;
? Subjects that were on a MTLDD RAS inhibitor and not on a diuretic (unless medically contraindicated) at the time of Screening must have been in Run-In for at least 2 weeks.
5. For entry into the Double-Blind Treatment Period, the subject must satisfy the following criteria based on the last visit of the Enrichment Period:
? RAS inhibitor at the MTLDD for the previous 6 weeks during the Enrichment Period with no adjustments of the dose;
? Diuretic at any dose unless medically contraindicated or clinically intolerable in the investigator's judgement (i.e., hypotension or hypokalemia);
? Weight change < 3 kg and absolute serum BNP < 300 pg/mL (300 ng/L) at Enrichment Week 6 from the beginning of Enrichment;
? Subjects must not have an AKI event at the end of the Enrichment period, as defined by an increase from baseline in serum Creatinine > 0.5 mg/dL and > 20% increase at Enrichment Week 6 (visit E5) from baseline.
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

1. Subject has a history of moderate or severe peripheral edema, pulmonary edema or facial edema unrelated to trauma or a history of myxedema in the prior 6 months to Screening.
2. Subject has a history of pulmonary hypertension requiring oxygen therapy, and/or endothelin receptor antagonist or phosphodiesterase therapy or any lung diseases requiring oxygen therapy (e.g., chronic obstructive pulmonary disease, emphysema, pulmonary fibrosis).
3. 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.
4. Subject has known non-diabetic kidney disease (other than kidney stones).
5. Subject has a history of symptomatic hypotension within the last 6 months.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The study objective is to evaluate the effect of atrasentan compared with placebo on time to doubling of serum creatinine or the onset of end stage renal disease (ESRD) in type 2 diabetic subjects with nephropathy who are treated with the maximum tolerated labeled dose (MTLD) of a Renin Angiotensin System (RAS) inhibitor.;Secondary Objective: The study will additionally assess the effects of atrasentan compared with placebo on cardiovascular morbidity and mortality, urine albumin excretion, changes in estimated glomerular filtration rate (eGFR), as well as on the impact on quality of life in type 2 diabetic subjects with nephropathy.;Primary end point(s): Time to the first occurrence of a component of the composite renal endpoint: doubling of serum creatinine (confirmed by a 30-day serum creatinine) or the onset of ESRD (needing chronic dialysis or renal transplantation or renal death).;Timepoint(s) of evaluation of this end point: End points are monitored throughout the study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): ? Change from baseline to Month 24 post-randomization visit on UACR.<br>? Time to a 30% eGFR reduction after 3 months post-randomization treatment.<br>? Time to cardio-renal composite endpoint: doubling of serum creatinine, ESRD, CV death, nonfatal myocardial infarction, nonfatal stroke.<br>? Time to the CV composite endpoint: CV death, nonfatal myocardial infarction and nonfatal stroke.;Timepoint(s) of evaluation of this end point: End points are monitored throughout the study

Related Trials