Dose Escalation Study to Investigate Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BAY85-3934 in Subjects With Chronic Kidney Disease (CKD)

Primary objective was to assess in subjects with CKD: Safety and tolerability of molidustat (BAY 85-3934), effects of molidustat on non-invasive hemodynamics Secondary objectives were to assess: Effects on pharmacodynamic parameters of erythropoiesis (erythropoietin, reticulocytes, erythrocytes, hemoglobin, hematocrit), pharmacokinetics of molidustat, exploratory biomarkers, ie, midregional pro-atrial natriuretic peptide, midregional pro-adrenomedullin, plasma renin activity, and optionally B-type natriuretic peptide, vascular endothelial growth factor, cyclic guanosine monophosphate, cyclic adenosine monophosphate, and noradrenaline


Eligibility Criteria:
Inclusion Criteria:

* Presence of chronic kidney disease (CKD) not on dialysis assessed by medical history and eGFR (MDRD) = \< 60 mL/min estimated at the pre-study visit
* Stable renal disease, ie not expected to begin dialysis during the study
* Systolic blood pressure =\>110 mmHg and =\<160 mmHg
* Heart rate =\<100 BPM
* Hemoglobin = \>9 g/dL
* Female subjects without child-bearing potential, ie postmenopausal women with 12 months of spontaneous amenorrhea or with 6 months of spontaneous amenorrhea and serum FSH levels \>30 mIU/mL, women with 6 weeks post bilateral ovariectomy, women with bilateral tubal ligation, and women with hysterectomy
* Body mass index (BMI): = \>18 and = \< 35 kg/m2 at the pre-study visit

Exclusion Criteria:

* Incompletely cured pre-existing diseases for which a relevant impairment of absorption, distribution, metabolism, elimination or effects of the study drug is assumed
* Known hypersensitivity to the study drugs (active substances or excipients of the preparations)
* Known severe allergies, non-allergic drug reactions, or multiple drug allergies
* Chronic heart failure, New York Heart Association (NYHA) III-IV
* Coronary artery disease with uncured significant stenosis
* Angina pectoris
* Significant stenosis of cerebral vessels
* Significant uncorrected rhythm or conduction disturbances such as a second- or third-degree atrioventricular block without a cardiac pacemaker or episodes of sustained ventricular tachycardia
* Subjects with impaired liver function (Child Pugh B to C based on medical history)
* History of thrombotic or thromboembolic events (eg myocardial infarction, stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism) within the recent 6 months
* Proliferative choroidal or retinal disease, such as neovascular age-related macular degeneration or proliferative diabetic retinopathy that required or is likely to require treatment (intraocular injections or laser photocoagulation) during the study
* Subjects with a history of malignant disease during the last 5 years
* Treatment with EPO-stimulating agents (ESA) or rhEPO within the last 2 weeks before first intake of study drug
* Suspicion of drug or alcohol abuse
* Positive results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), human immune deficiency virus antibodies (anti-HIV 1+2) at the pre-study visit