check_circleStudy 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
  • - 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
  • - 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
49
Trial Dates
September 2012 - July 2013
Phase
Phase 1
Could I Receive a placebo
Yes
Products
Molidustat (BAY85-3934)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Kiel, 24105, Germany
Completed
Mönchengladbach, 41061, Germany
Completed
München, 81241, Germany

Primary Outcome

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

Secondary Outcome

  • Change of hematology profile
    Hematology profile includes blood concentration of erythropoietin, reticulocytes, erythrocytes, hemoglobin, hematocrit, and exploratory biomarkers.
    date_rangeTime Frame:
    From baseline to Day 1 after single dose
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    Safety Issue:
    No
  • Cmax,norm
    Cmax divided by dose per body weight
    date_rangeTime Frame:
    Pre-dose and up to 48 h post-dose
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    Safety Issue:
    No
  • AUCnorm
    AUC divided by dose per body weight
    date_rangeTime Frame:
    Pre-dose and up to 48 h post-dose
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    Safety Issue:
    No
  • AUC(0-24)
    AUC from 0 until 24 h after study drug administration
    date_rangeTime Frame:
    Pre-dose and up to 24 h post-dose
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    Safety Issue:
    No
  • AUC(0-tlast)
    AUC from time 0 to the last data point > lower limit of quantification
    date_rangeTime Frame:
    Pre-dose and up to 48 h post-dose
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    Safety Issue:
    No
  • t½
    Half-life associated with the terminal slope
    date_rangeTime Frame:
    Pre-dose and up to 48 h post-dose
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    Safety Issue:
    No
  • tmax
    Time to reach Cmax (in case of two identical Cmax values, the first tmax was used)
    date_rangeTime Frame:
    Pre-dose and up to 48 h post-dose
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    Safety Issue:
    No
  • MRT
    Mean residence time
    date_rangeTime Frame:
    Pre-dose and up to 48 h post-dose
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    Safety Issue:
    No
  • CL/F
    Total body clearance of drug calculated after extravascular administration (eg, apparent oral clearance)
    date_rangeTime Frame:
    Pre-dose and up to 48 h post-dose
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    Safety Issue:
    No
  • Vz/F
    Apparent volume of distribution during terminal phase after extravascular administration
    date_rangeTime Frame:
    Pre-dose and up to 48 h post-dose
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    Safety Issue:
    No
  • Geometric mean erythropoietin Cmax
    date_rangeTime Frame:
    Pre-dose and up to 24 h post-dose
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    Safety Issue:
    Yes
  • Geometric mean reticulocyte count
    date_rangeTime Frame:
    Pre-dose and up to 24 h post-dose
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    Safety Issue:
    Yes
  • Geometric mean erythrocyte count
    date_rangeTime Frame:
    Pre-dose and up to 24 h post-dose
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    Safety Issue:
    Yes
  • Geometric mean reticulocytes/erythrocytes values
    date_rangeTime Frame:
    Pre-dose and up to 24 h post-dose
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    Safety Issue:
    Yes
  • Geometric mean hemoglobin values
    date_rangeTime Frame:
    Pre-dose and up to 24 h post-dose
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    Safety Issue:
    Yes
  • Geometric mean hematocrit
    date_rangeTime Frame:
    Pre-dose and up to 24 h post-dose
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    Safety Issue:
    Yes
  • Geometric mean erythropoietin tmax
    date_rangeTime Frame:
    Pre-dose and up to 24 h post-dose
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    Safety Issue:
    No
  • Geometric mean erythropoietin AUC(0-24)
    date_rangeTime Frame:
    Pre-dose and up to 24 h post-dose
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    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
4

Additional Information

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