Diabetic Nephropathy
Conditions
Interventions
investigational material(s)
Generic name etc : ABT-627
INN of investigational material : -
Therapeutic category code : 219 Other cardiovascular agents
Dosage and Administration for Investigational m
Sponsors
AbbVie GK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: * 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. * For entry into the Run-In Period, the subject must satisfy the following criteria Screening laboratory values: -Estimated glomerular filtration rate (eGFR) 25 to 75 mL/min/1.73 m2 and a urine albumin creatinine ratio (UACR) greater than or equal to 300 and less than 5,000 mg/g (greater than or equal to 34 mg/mmol and less than 565 mg/mmol). -Serum albumin greater than or equal to 2.5 g/dL (25 g/L). -Brain natriuretic peptide (BNP) less than or equal to 200 pg/mL (200 ng/L). -Systolic blood pressure (SBP) greater than or equal to 110 and less than or equal to 180 mmHg. -Serum Potassium greater than or equal to 3.5 mEq/L (3.5 mmol/L) and less than or equal to 6.0 mEq/L (6.0 mmol/L). Subjects on a maximum tolerated labeled daily dose (MTLDD) of a RAS inhibitor for greater than or equal to 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 greater than or equal to 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. * 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. * 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); - Subject must not have a weight change greater than or equal to 3 kg from the beginning of Enrichment to the end of the Enrichment Period and absolute serum BNP greater than or equal to 300 pg/mL (300 ng/L) at the last Enrichment visit; - Subject must not have an increase in serum creatinine greater than 0.5 mg/dL (greater than 48 umol/L) and greater than 20% increase from the beginning of Enrichment to the end of the Enrichment Period.
Exclusion criteria
Exclusion criteria: 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 diseases 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety efficacy Time to the first occurrence of a component of the composite renal endpoint. [ Time 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 end stage renal disease (needing chronic dialysis or renal transplantation or renal death). | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy - Time to a 50% estimated glomerular filtration rate reduction. - Time to cardio-renal composite endpoint: confirmed doubling of serum creatinine, end stage renal disease, cardiovascular death, nonfatal myocardial infarction, nonfatal stroke. - Time to the cardiovascular composite endpoint: cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. - Time to first occurrence of a component of composite renal endpoint: confirmed doubling of serum creatinine or the onset of end stage renal disease for all randomized subjects (pooled). | — |
Countries
Asia except Japan, Europe, Japan, North America, South America
Outcome results
None listed