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

April 29, 2016 updated by: Bayer

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)

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Bayern
      • München, Bayern, Germany, 81241
    • Nordrhein-Westfalen
      • Mönchengladbach, Nordrhein-Westfalen, Germany, 41061
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Molidustat, 80 mg
Subjects received a single oral dose of 80 mg BAY 85-3934 in the first period and placebo in the second period, separated by a wash-out period of at least 1 week.
Drug: Molidustat (BAY85-3934)
20 mg molidustat as a single tablet
Drug: Placebo
Single oral dose of matching placebo will be given in each treatment arm
Experimental: Molidustat, 120 mg
Subjects received a single oral dose of 120 mg BAY 85-3934 in the first period and placebo in the second period, separated by a wash-out period of at least 1 week.
Drug: Molidustat (BAY85-3934)
20 mg molidustat as a single tablet
Drug: Placebo
Single oral dose of matching placebo will be given in each treatment arm
Experimental: Molidustat, 40 mg
Subjects received a single oral dose of 40 mg BAY 85-3934 in the first period and placebo in the second period, separated by a wash-out period of at least 1 week. This is an optional dose escalation step.
Drug: Molidustat (BAY85-3934)
20 mg molidustat as a single tablet
Drug: Placebo
Single oral dose of matching placebo will be given in each treatment arm
Experimental: Molidustat, 160 mg
Subjects received a single oral dose of 160 mg BAY 85-3934 in the first period and placebo in the second period, separated by a wash-out period of at least 1 week. This is an optional dose escalation step.
Drug: Molidustat (BAY85-3934)
20 mg molidustat as a single tablet
Drug: Placebo
Single oral dose of matching placebo will be given in each treatment arm

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events
Time Frame: Approximately 9 weeks
Approximately 9 weeks
Blood pressure
Time Frame: Approximately 9 weeks
Systolic, diastolic, mean blood pressure
Approximately 9 weeks
Heart rate
Time Frame: Approximately 9 weeks
Approximately 9 weeks
Cmax
Time Frame: Pre-dose and up to 48 h post-dose
Maximum observed drug concentration in measured matrix after single dose administration
Pre-dose and up to 48 h post-dose
Cmax/D
Time Frame: Pre-dose and up to 48 h post-dose
Cmax divided by dose
Pre-dose and up to 48 h post-dose
AUC
Time Frame: Pre-dose and up to 48 h post-dose
Area under the concentration vs time curve from zero to infinity after single dose
Pre-dose and up to 48 h post-dose
AUC/D
Time Frame: Pre-dose and up to 48 h post-dose
AUC divided by dose
Pre-dose and up to 48 h post-dose
Heart rate over 1 min
Time Frame: Pre-dose and up to 24 h post-dose
Pre-dose and up to 24 h post-dose
Standing blood pressure procedure
Time Frame: Starting from 2 h post-dose and up to 4 h post-dose
Starting from 2 h post-dose and up to 4 h post-dose
Impedance cardiography
Time Frame: Pre-dose and up tp 8 h post-dose
Stroke volume, heart rate, cardiac index, cardiac output, and total peripheral resistance
Pre-dose and up tp 8 h post-dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change of hematology profile
Time Frame: From baseline to Day 1 after single dose
Hematology profile includes blood concentration of erythropoietin, reticulocytes, erythrocytes, hemoglobin, hematocrit, and exploratory biomarkers.
From baseline to Day 1 after single dose
Cmax,norm
Time Frame: Pre-dose and up to 48 h post-dose
Cmax divided by dose per body weight
Pre-dose and up to 48 h post-dose
AUCnorm
Time Frame: Pre-dose and up to 48 h post-dose
AUC divided by dose per body weight
Pre-dose and up to 48 h post-dose
AUC(0-24)
Time Frame: Pre-dose and up to 24 h post-dose
AUC from 0 until 24 h after study drug administration
Pre-dose and up to 24 h post-dose
AUC(0-tlast)
Time Frame: Pre-dose and up to 48 h post-dose
AUC from time 0 to the last data point > lower limit of quantification
Pre-dose and up to 48 h post-dose
t½
Time Frame: Pre-dose and up to 48 h post-dose
Half-life associated with the terminal slope
Pre-dose and up to 48 h post-dose
tmax
Time Frame: Pre-dose and up to 48 h post-dose
Time to reach Cmax (in case of two identical Cmax values, the first tmax was used)
Pre-dose and up to 48 h post-dose
MRT
Time Frame: Pre-dose and up to 48 h post-dose
Mean residence time
Pre-dose and up to 48 h post-dose
CL/F
Time Frame: Pre-dose and up to 48 h post-dose
Total body clearance of drug calculated after extravascular administration (eg, apparent oral clearance)
Pre-dose and up to 48 h post-dose
Vz/F
Time Frame: Pre-dose and up to 48 h post-dose
Apparent volume of distribution during terminal phase after extravascular administration
Pre-dose and up to 48 h post-dose
Geometric mean erythropoietin Cmax
Time Frame: Pre-dose and up to 24 h post-dose
Pre-dose and up to 24 h post-dose
Geometric mean reticulocyte count
Time Frame: Pre-dose and up to 24 h post-dose
Pre-dose and up to 24 h post-dose
Geometric mean erythrocyte count
Time Frame: Pre-dose and up to 24 h post-dose
Pre-dose and up to 24 h post-dose
Geometric mean reticulocytes/erythrocytes values
Time Frame: Pre-dose and up to 24 h post-dose
Pre-dose and up to 24 h post-dose
Geometric mean hemoglobin values
Time Frame: Pre-dose and up to 24 h post-dose
Pre-dose and up to 24 h post-dose
Geometric mean hematocrit
Time Frame: Pre-dose and up to 24 h post-dose
Pre-dose and up to 24 h post-dose
Geometric mean erythropoietin tmax
Time Frame: Pre-dose and up to 24 h post-dose
Pre-dose and up to 24 h post-dose
Geometric mean erythropoietin AUC(0-24)
Time Frame: Pre-dose and up to 24 h post-dose
Pre-dose and up to 24 h post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 3, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 6, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 2, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16370
  • 2012-002375-33 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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