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

• Status: Completed
• Trial end date: 2013-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bayer

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