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Kidney DiseasesPhase 1NCT01679587

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

A Phase 1 study testing Molidustat (BAY85-3934) in people with Kidney Diseases, run by Bayer at 3 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 79 years
Conditions the study is for
Kidney Diseases
What is being tested?
Molidustat (BAY85-3934)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
49 participants
Where
3 sitesGermany
Study dates
Sep 2012to Jul 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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 locations and contacts

3 sites in 1 country.

Germany3 sites

  • Study site

    Kiel, Schleswig-Holstein, 24105

  • Study site

    Mönchengladbach, North Rhine-Westphalia, 41061

  • Study site

    München, Bavaria, 81241

Other trials in Germany

About this study

Official title: 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

Conditions
Kidney Diseases
Being tested
Molidustat (BAY85-3934), Placebo
Medical subject headings
Kidney Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Molidustat (BAY85-3934)Drug

    20 mg molidustat as a single tablet

  • PlaceboDrug

    Single oral dose of matching placebo will be given in each treatment arm

Study groups in NCT01679587
Study groupRoleWhat they receive
Molidustat, 80 mgExperimentalSubjects 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.
Receives: Drug: Molidustat (BAY85-3934); Drug: Placebo
Molidustat, 120 mgExperimentalSubjects 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.
Receives: Drug: Molidustat (BAY85-3934); Drug: Placebo
Molidustat, 40 mgExperimentalSubjects 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.
Receives: Drug: Molidustat (BAY85-3934); Drug: Placebo
Molidustat, 160 mgExperimentalSubjects 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.
Receives: Drug: Molidustat (BAY85-3934); Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with adverse events

    Measured: Approximately 9 weeks

  2. Blood pressure

    Systolic, diastolic, mean blood pressure

    Measured: Approximately 9 weeks

  3. Heart rate

    Measured: Approximately 9 weeks

  4. Cmax

    Maximum observed drug concentration in measured matrix after single dose administration

    Measured: Pre-dose and up to 48 h post-dose

  5. Cmax/D

    Cmax divided by dose

    Measured: Pre-dose and up to 48 h post-dose

  6. AUC

    Area under the concentration vs time curve from zero to infinity after single dose

    Measured: Pre-dose and up to 48 h post-dose

  7. AUC/D

    AUC divided by dose

    Measured: Pre-dose and up to 48 h post-dose

  8. Heart rate over 1 min

    Measured: Pre-dose and up to 24 h post-dose

  9. Standing blood pressure procedure

    Measured: Starting from 2 h post-dose and up to 4 h post-dose

  10. Impedance cardiography

    Stroke volume, heart rate, cardiac index, cardiac output, and total peripheral resistance

    Measured: Pre-dose and up tp 8 h post-dose

Secondary outcomes (18)

  1. Change of hematology profile

    Hematology profile includes blood concentration of erythropoietin, reticulocytes, erythrocytes, hemoglobin, hematocrit, and exploratory biomarkers.

    Measured: From baseline to Day 1 after single dose

  2. Cmax,norm

    Cmax divided by dose per body weight

    Measured: Pre-dose and up to 48 h post-dose

  3. AUCnorm

    AUC divided by dose per body weight

    Measured: Pre-dose and up to 48 h post-dose

  4. AUC(0-24)

    AUC from 0 until 24 h after study drug administration

    Measured: Pre-dose and up to 24 h post-dose

  5. AUC(0-tlast)

    AUC from time 0 to the last data point > lower limit of quantification

    Measured: Pre-dose and up to 48 h post-dose

  6. t½

    Half-life associated with the terminal slope

    Measured: Pre-dose and up to 48 h post-dose

  7. tmax

    Time to reach Cmax (in case of two identical Cmax values, the first tmax was used)

    Measured: Pre-dose and up to 48 h post-dose

  8. MRT

    Mean residence time

    Measured: Pre-dose and up to 48 h post-dose

  9. CL/F

    Total body clearance of drug calculated after extravascular administration (eg, apparent oral clearance)

    Measured: Pre-dose and up to 48 h post-dose

  10. Vz/F

    Apparent volume of distribution during terminal phase after extravascular administration

    Measured: Pre-dose and up to 48 h post-dose

  11. Geometric mean erythropoietin Cmax

    Measured: Pre-dose and up to 24 h post-dose

  12. Geometric mean reticulocyte count

    Measured: Pre-dose and up to 24 h post-dose

  13. Geometric mean erythrocyte count

    Measured: Pre-dose and up to 24 h post-dose

  14. Geometric mean reticulocytes/erythrocytes values

    Measured: Pre-dose and up to 24 h post-dose

  15. Geometric mean hemoglobin values

    Measured: Pre-dose and up to 24 h post-dose

  16. Geometric mean hematocrit

    Measured: Pre-dose and up to 24 h post-dose

  17. Geometric mean erythropoietin tmax

    Measured: Pre-dose and up to 24 h post-dose

  18. Geometric mean erythropoietin AUC(0-24)

    Measured: Pre-dose and up to 24 h post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Sep 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionFeb 2013
  4. Study completionJul 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01679587
Sponsor's protocol ID
16370
Other IDs
2012-002375-33
Status last verified
Apr 2016
First submitted
3 Sep 2012
Last updated
2 May 2016
Results posted
No
Data monitoring committee
No

Publications

  • Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

    PubMed 36005278

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Molidustat (BAY85-3934) in people with Kidney Diseases, run by Bayer at 3 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with adverse events (time frame: Approximately 9 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01679587, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2016.

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