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

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. 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 [until the eGFR cap on
subjects (approximately 300) with a baseline of > 60 mL/min/1.73 m2
is reached] 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 = 6.0 mEq/L (6.0 mmol/L);
• 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 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:
• 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 judgement (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 2656
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2844

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).
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

Secondary Outcome Measures

Name	Time	Method

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