Study Completed

Kidney Diseases

Bayer Identifier:

16370

ClinicalTrials.gov Identifier:

NCT01679587

EudraCT Number:

2012-002375-33

EU CT Number:

Not Available

Dose escalation study to investigate safety, tolerability, pharmacodynamics, and pharmacokinetics of BAY85-3934 in subjects with chronic kidney disease (CKD)

Trial purpose

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

Key Participants Requirements

Sex

Both

Age

18 - 79 Years

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

Trial summary

Enrollment Goal

Trial Dates

September 2012 - July 2013

Phase

Phase 1

Could I Receive a placebo

Yes

Products

Molidustat (BAY85-3934)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed		Kiel, 24105, Germany
Completed		Mönchengladbach, 41061, Germany
Completed		München, 81241, Germany

Primary Outcome

Number of participants with adverse events
Time Frame:
Approximately 9 weeks
Safety Issue:
Yes
Blood pressure
Systolic, diastolic, mean blood pressure
Time Frame:
Approximately 9 weeks
Safety Issue:
Yes
Heart rate
Time Frame:
Approximately 9 weeks
Safety Issue:
Yes
Cmax
Maximum observed drug concentration in measured matrix after single dose administration
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
Cmax/D
Cmax divided by dose
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
AUC
Area under the concentration vs time curve from zero to infinity after single dose
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
AUC/D
AUC divided by dose
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
Heart rate over 1 min
Time Frame:
Pre-dose and up to 24 h post-dose
Safety Issue:
No
Standing blood pressure procedure
Time Frame:
Starting from 2 h post-dose and up to 4 h post-dose
Safety Issue:
No
Impedance cardiography
Stroke volume, heart rate, cardiac index, cardiac output, and total peripheral resistance
Time Frame:
Pre-dose and up tp 8 h post-dose
Safety Issue:
No

Secondary Outcome

Change of hematology profile
Hematology profile includes blood concentration of erythropoietin, reticulocytes, erythrocytes, hemoglobin, hematocrit, and exploratory biomarkers.
Time Frame:
From baseline to Day 1 after single dose
Safety Issue:
No
Cmax,norm
Cmax divided by dose per body weight
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
AUCnorm
AUC divided by dose per body weight
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
AUC(0-24)
AUC from 0 until 24 h after study drug administration
Time Frame:
Pre-dose and up to 24 h post-dose
Safety Issue:
No
AUC(0-tlast)
AUC from time 0 to the last data point > lower limit of quantification
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
t½
Half-life associated with the terminal slope
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
tmax
Time to reach Cmax (in case of two identical Cmax values, the first tmax was used)
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
MRT
Mean residence time
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
CL/F
Total body clearance of drug calculated after extravascular administration (eg, apparent oral clearance)
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
Vz/F
Apparent volume of distribution during terminal phase after extravascular administration
Time Frame:
Pre-dose and up to 48 h post-dose
Safety Issue:
No
Geometric mean erythropoietin Cmax
Time Frame:
Pre-dose and up to 24 h post-dose
Safety Issue:
Yes
Geometric mean reticulocyte count
Time Frame:
Pre-dose and up to 24 h post-dose
Safety Issue:
Yes
Geometric mean erythrocyte count
Time Frame:
Pre-dose and up to 24 h post-dose
Safety Issue:
Yes
Geometric mean reticulocytes/erythrocytes values
Time Frame:
Pre-dose and up to 24 h post-dose
Safety Issue:
Yes
Geometric mean hemoglobin values
Time Frame:
Pre-dose and up to 24 h post-dose
Safety Issue:
Yes
Geometric mean hematocrit
Time Frame:
Pre-dose and up to 24 h post-dose
Safety Issue:
Yes
Geometric mean erythropoietin tmax
Time Frame:
Pre-dose and up to 24 h post-dose
Safety Issue:
No
Geometric mean erythropoietin AUC(0-24)
Time Frame:
Pre-dose and up to 24 h post-dose
Safety Issue:
No

Trial design

Multicenter, randomized, single-blind, placebo-controlled, combined 2-fold cross-over and group-comparison, dose-escalation study to investigate safety, tolerability, pharmacodynamics, and pharmacokinetics of single oral doses of BAY 85-3934 in subjects with chronic kidney disease (CKD)

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Other

Allocation

Randomized

Blinding

Single Blind

Assignment

Crossover Assignment

Trial Arms

Additional Information

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