AnemiaPhase 1NCT01332942
Combined Single / Multiple Dose Escalation Study in Patients With Renal Anemia Due to CKD (Chronic Kidney Disease)
A Phase 1 study testing BAY85-3934 in people with Anemia, run by Bayer at 11 sites in 2 countries.
Trial summary
The drug that is under investigation during this study is BAY85-3934 which is intended to be used as a treatment for patients suffering from renal anemia due to chronic kidney disease (stage 3 and 4). The purpose of this study is to provide safety and tolerability information on the drug. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Anemia
- What is being tested?
- BAY85-3934
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 11 sitesin 2 countries
- Study dates
- Apr 2011to Dec 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The informed consent must be signed before any study specific tests or procedures are done
- Renal anemia due to CKD (stage 3 and 4) not on dialysis assessed by medical history and Creatine Clearance (CLCR) between 15 to 59 mL/min ± 10 % (ie CLCR between 13 - 65 mL/min) estimated at the pre-study visit from the creatinine concentration measured in serum (Modification of Diet in Renal Disease (MDRD) formula)
- Stable renal disease, ie without major changes in therapy within the last 6 weeks and not expected to begin dialysis within the study.
- Female subjects with no child-bearing potential (postmenopausal women with 12 month of spontaneous amenorrhea or with 6 month of spontaneous amenorrhea and serum FSH levels > 30 mIU/mL, women with 6 weeks post bilateral ovariectomy, woman with bilateral tubal ligation, and women with hysterectomy).
- Male subjects who agree to use two forms of effective contraception during the study and for 12 weeks after receiving the study drug. This must include a condom with spermicide gel for 21 days after drug administration.
- Male subjects who agree not to act as sperm donors for 12 weeks after dosing.
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- Age: ≥ 18 and ≤ 85 years at the pre-study visit
- Body mass index (BMI): ≥ 18 and ≤ 35 kg / m2 at the pre-study visit
- Hemoglobin (Hb) of 8.0 - 12 g/dL (male) or 8.0 - 11.5 g/dL (female) at two consecutive measurements (1 measurement performed within 12 weeks to 2 days before the pre-study visit during routine diagnostics independently of the study and 1 measurement at the pre-study visit)
- Ability to understand and follow study-related instructions
Who cannot join
- Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal
- Known hypersensitivity to the study drugs (active substances or excipients of the preparations)
- Known severe allergies, non-allergic drug reactions, or multiple drug allergies
- Patients with impaired liver function (Child Pugh B and C based on medical history)
- Patients with hemolysis/hemolytic anemia or active bleeding/blood loss
- Major surgery or an intervention causing relevant blood loss or inflammation within the last 2 month
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- Planned intervention or surgery during the study which might impact the study objectives.
- Febrile illness within 1 week before the first study drug administration or clinically significant infection.
- Patients with chronic inflammatory diseases (eg systemic lupus erythematosis, rheumatoid arthritis, Crohn´s disease) that could impact erythropoiesis or with persistent inflammatory activity (eg C-reactive protein (CRP) > 20mg/L)
- History of thrombotic or thromboembolic events (e.g. 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.
- History of myelodysplastic syndrome, multiple myeloma, bone marrow fibrosis, or pure red cell aplasia.
- History of hemosiderosis or hemochromatosis.
- Patients with a history of malignant disease during the last 5 years
- Treatment with erythropoiesis stimulating agents (ESA) within the last 4 weeks before first intake of study drug
- Intravenous iron substitution 2 weeks before and during the treatment period with BAY 85-3934
- RBC transfusion during previous 8 weeks
- Use of products containing carnitine and/or anabolics
- Use of medicines or substances which oppose the study objectives or which might influence them within 14 days before the first study drug administration
- Significant uncorrected rhythm or conduction disturbances such as a second- or third-degree AV block without a cardiac pacemaker or episodes of sustained ventricular tachycardia
- Systolic blood pressure below 100 or above 160 mmHg at the pre-study visit
- Diastolic blood pressure below 50 or above 100 mmHg at the pre-study visit
- 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
- Heart rate above 110 bpm
- Ferritin levels ≤ 30 ng/mL at the pre-study visit
- Transferrin-saturation < 15% at the pre-study visit
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
Germany10 sites
Study site
Berlin, State of Berlin, 10117
Study site
Berlin, State of Berlin, 13125
Study site
Cologne, North Rhine-Westphalia, 50931
Study site
Düsseldorf, North Rhine-Westphalia, 40225
Study site
Hamburg, Free and Hanseatic City of Hamburg, 20253
Study site
Hanover, Lower Saxony, 30159
Study site
Hanover, Lower Saxony, 30625
Study site
Kiel, Schleswig-Holstein, 24105
Study site
München, Bavaria, 81241
Study site
Wuppertal, 42283
About this study
Official title: Randomized, Single-blind, Placebo-controlled, Combined Single / Multiple Dose Escalation, Group Comparison Study to Investigate Safety, Tolerability, Pharmacodynamic Effect and Pharmacokinetics of BAY 85-3934 in Patients With Renal Anemia Due to CKD (Stages 3 and 4)
The drug that is under investigation during this study is BAY85-3934 which is intended to be used as a treatment for patients suffering from renal anemia due to chronic kidney disease (stage 3 and 4).
The purpose of this study is to provide safety and tolerability information on the drug. Other objectives of the study are to investigate the effect of the drug on the body (pharmacodynamics) as well as the absorption, breakdown, metabolism, distribution and excretion (pharmacokinetics) by measuring the concentration in blood and urine.
The study will be conducted in one study center in the United Kingdom and several centers in Germany. 84 (of which 36 are optional) patients who meet the inclusion criteria will participate in the study. BAY 85-3934 will be given following a combined single / multiple dose escalation design in seven (of which three are optional) dose steps.
- Conditions
- Anemia
- Being tested
- BAY85-3934
- Keywords
- Anemia
- Medical subject headings
- Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY85-3934Drug
Subjects received an oral single dose of placebo tablet matched to the molidustat dose (BAY85-3934) on Day 1 followed by a washout day and once daily multipledose over 12 days (from Day 3 to Day 14).
BAY85-3934Drug
Subjects received an oral single dose of 5 mg of molidustat IR tablet on Day 1 followed by a washout day and once daily multiple-dose over 12 days (from Day 3 to Day 14).
BAY85-3934Drug
Subjects received an oral single dose of 10 mg of molidustat ( 2x 5mg IR tablets) on Day 1 followed by a washout day and once daily multipledose over 12 days (from Day 3 to Day 14).
BAY85-3934Drug
Subjects received an oral single dose of 25 mg of molidustat (1 x 20 mg IR tablet and 1 x 5 mg IR tablet) on Day 1 followed by a washout day and once daily multiple-dose over 12 days (from Day 3 to Day 14).
BAY85-3934Drug
Subjects received an oral single dose of 50 mg) of molidustat (2 x 20 mg IR tablets and 2 x 5 mg IR tablets) on Day 1 followed by a washout day and once daily multiple-dose over 12 days (from Day 3 to Day 14).
BAY85-3934Drug
Subjects received an oral single dose of 75 mg of molidustat (3 x 20 mg IR tablets and 3 x 5 mg IR tablets) on Day 1 followed by a washout day and once daily multiple-dose over 12 days (from Day 3 to Day 14).
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: BAY85-3934 |
| Molidustat (BAY85-3934) 5 mg | Experimental | Not described Receives: Drug: BAY85-3934 |
| Molidustat (BAY85-3934) 10 mg | Experimental | Not described Receives: Drug: BAY85-3934 |
| Molidustat (BAY85-3934) 25 mg | Experimental | Not described Receives: Drug: BAY85-3934 |
| Molidustat (BAY85-3934) 50 mg | Experimental | Not described Receives: Drug: BAY85-3934 |
| Molidustat (BAY85-3934) 75 mg | Experimental | Not described Receives: Drug: BAY85-3934 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects with Treatment-Emergent Adverse Events (TEAE)
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important serious event. TEAEs were defined as AEs/SAEs that started or worsened after the study drug treatment.
Measured: From start of study drug administration until last follow-up visit (14 days after the last study drug administration)
Mean Change in Heart Rate Within 4 hours Post-dose
Heart rate was observed in all treatment groups in supine position.
Measured: Within 4 hours from after administration of study drug on Day 1 and Day 14
Mean Change in Heart Rate Over 1 Minute for Doses 25, 50, 75 Milligrams
Heart rate was assessed over 1 minute from the Electrocardiogram (ECG) recording.
Measured: From start of study drug administration until 12 hours after the last study drug administration
Mean Change in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Within 4 hours Post-dose
SBP, DBP was observed in all treatment groups in supine phase.
Measured: Within 4 hours post-dose at Day 1 and Day 14
Number of Subjects with Clinically Relevant Abnormal Findings in the Electrocardiogram (ECG)
Electrocardiograms were recorded and analyzed by an electronic ECG reading system.
Measured: Day 1 and Day 14
Number of Subjects with Clinically Relevant Laboratory Values
Laboratory parameters include hematology, coagulation, serum chemistry, urinalysis.
Measured: Day 1 and Day 14
Maximum Observed Drug Concentration (Cmax) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Cmax refers to the highest measured drug concentration after a single dose which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Maximum Observed Drug Concentration Divided by Dose (Cmax/D) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Cmax/D is defined as maximum observed drug concentration divided by dose. Cmax refers to the highest measured drug concentration after single dose which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
AUC is a measure of systemic drug exposure after single dose, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC is defined as area under concentration versus time curve from time 0 (pre-dose) to extrapolated infinite time. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Area Under the Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
AUC is a measure of systemic drug exposure after single dose, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC is defined as area under concentration versus time curve from time 0 (pre-dose) to extrapolated infinite time. AUC/D is defined as area under the concentration versus time curve from zero to infinity divided by dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Maximum Observed Drug Concentration (Cmax,md) in Plasma of Molidustat and its Metabolite After Multiple Dose Administration of Molidustat
Cmax,md defined as maximum observed drug concentration after multiple dose. Cmax,md refers to the highest measured drug concentration in the dosing interval which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Maximum Observed Drug Concentration in Plasma Divided by Dose (Cmax,md/D) of Molidustat and its Metabolite After Multiple Dose Administration of Molidustat
Cmax,md/D is defined as maximum observed drug concentration divided by dose after multiple dose administration. Cmax,md refers to the highest measured drug concentration within the dosing interval which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Area Under the Concentration Versus Time Curve From 0 to 24 hour (AUC[0-24]md) in Plasma During any Dose Interval of Molidustat and its Metabolite After Multiple Dose of Molidustat
AUC(0-24)md is defined as area under the concentration versus time curve from 0 to 24 hour after multiple dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Area Under the Concentration Versus Time Curve From 0 to 24 hour Divided by Dose (AUC[0-24] md/D) in Plasma During any Dose Interval of Molidustat and its Metabolite After Multiple Dose of Molidustat
AUC(0-24)md/D is defined as area under the concentration versus time curve from 0 to 24 hour divided by dose after multiple dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Secondary outcomes (30)
Maximum Observed Drug Concentration in Plasma Divided by Dose per Kilogram Body Weight (Cmax,norm) of Molidustat and its Metabolite After Single Dose of Molidustat
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Cmax,norm is defined as maximum observed drug concentration divided by dose per kilogram body weight. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Area Under the Concentration Versus Time Curve From Zero to Infinity in Plasma Divided by Dose per Kilogram Body Weight (AUCnorm) of Molidustat and its Metabolite After Single Dose of Molidustat
AUC is a measure of systemic drug exposure after single dose, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUCnorm is defined as area under the concentration versus time curve from zero to infinity divided by dose per kilogram body weight. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Area Under the Concentration Versus Time Curve From Zero to 24 hour (AUC[0-24]) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
AUC(0-24) is defined as area under the concentration versus time curve from zero to 24 hours after a single dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-24 hours post-dose
Area Under the Concentration Versus Time Curve From Zero to the Last Data Point Above the Lower Limit of Quantification (AUC[0-tlast]) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
AUC is a measure of systemic drug exposure after single dose, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC(0-tlast) is defined as AUC from time zero to the last data point above the lower limit of quantification. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Half Life Associated With the Terminal Slope (t1/2) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Half life associated with terminal slope. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase. It is expressed in hours and derived from the terminal slope of the concentration versus time curve. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Time to Reach Maximum Drug Concentration (tmax) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. Median and range were reported.
Measured: Single dose: 0-48 hours post-dose
Mean Residence Time (MRT) of Molidustat and its Metabolite After Single Dose of Molidustat
MRT is an average duration of the drug in the body, and is expressed in hours. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Apparent Oral Clearance (CL/F) of Molidustat and its Metabolite After Single Dose of Molidustat
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Apparent Volume of Distribution During Terminal Phase (Vz/F) After Single Dose of Molidustat
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the observed plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: 0-48 hours post-dose
Amount Excreted into Urine (Aeur) of Molidustat and its Metabolite After Single Dose of Molidustat
Aeur refers to the amount of molidustat excreted in urine.
Measured: Urine collection intervals: 0d00 - 0d12h, 0d12h - 1d00
Renal Body Clearance of Drug (CLR) of Molidustat and its Metabolite After Single Dose of Molidustat
Renal clearance describes the removal of drug from a volume of plasma in a given unit of time by the kidneys. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Urine collection interval: 0d00 - 1d00
Maximum Observed Concentration Divided by Dose per Kilogram Body Weight (Cmax,md,norm) in Plasma After Multiple Dose Administration During a Dosage Interval
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Cmax,md,norm is defined as maximum observed concentration during a given dosing interval divided by dose per kilogram body weight in plasma after multiple dose administration. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Area Under the Concentration Versus Time Curve From 0 to 24 hour Divided by Dose per Kilogram Body Weight (AUC[0-24]md,norm) in Plasma After Multiple Dose Administration During a Dosage Interval
AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC(0-24) md,norm is defined as area under the concentration versus time curve from 0 to 24 hour divided by dose per kilogram body weight after multiple dose administration. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Half Life Associated With the Terminal Slope (t1/2,md) in Plasma of Molidustat and its Metabolite After Multiple Dose of Molidustat
Half life associated with terminal slope. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase. It is expressed in hours and derived from the terminal slope of the concentration versus time curve. t1/2,md is defined as half life associated with the terminal slope after multiple dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Time to Reach Maximum Drug Concentration (tmax,md) in Plasma of Molidustat and its Metabolite After Multiple Dose of Molidustat
tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. tmax,md is defined as time to reach maximum drug concentration after multiple dose. Median and range were reported.
Measured: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Amount Excreted into Urine (Aeur,md)of Molidustat and its Metabolite After Multiple Dose of Molidustat
Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Urine collection interval: 13d00 - 14d00
Renal Body Clearance (CLR,md) of Molidustat and its Metabolite After Multiple Dose of Molidustat
Renal clearance describes the removal of drug from a volume of plasma in a given unit of time by the kidneys. CLR,md is defined as renal body clearance of drug after multiple dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Urine collection interval: 13d00 - 14d00
Accumulation Ratio of AUC in the Dosing Interval (RAAUC) of Molidustat
RAAUC was calculated by using formula AUC(0-24)[13day] / AUC(0-24)[0day].
Measured: All samples from 0-24h on 0d and from 0-24h on 13d
Accumulation Ratio of Cmax (RACmax) of Molidustat
RACmax was calculated by using formula Cmax[13day] / Cmax[0day].
Measured: All samples from 0-24h on 0d and from 0-24h on 13d
Linearity Factor of Pharmacokinetics After Repeated Administration of Identical Doses (RLin) of Molidustat
RLin was calculated by using formula AUC(0-24)[13day] / AUC[0day].
Measured: All samples from 0-24h on 0d and from 0-24h on 13d
Erythropoietin Concentration: Area Under the Concentration Versus Time Curve From 0 to 24 hour (AUC[0-24]) Post-dose on Day 1 (0d)
AUC(0-24) is defined as area under the concentration versus time curve from zero to 24 hours after a single dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: Pre-dose and 4, 8, 12 and 24 hours post-dose
Erythropoietin Concentration: Area Under the Concentration Versus Time Curve From 0 to 24 hour (AUC[0-24]md) in Plasma After Multiple Dose on Day 14 (13d)
Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Multiple dose: Pre-dose and 4, 8, 12 and 24 hours post-dose on 13day
Erythropoietin Concentration: Maximum Observed Drug Concentration in Plasma (Cmax[0-24]) After Single Dose of Molidustat on Day 1 (0d)
Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Single dose: Pre-dose and 4, 8, 12, 24 hours post-dose
Erythropoietin Concentration: Maximum Observed Drug Concentration in Plasma (Cmax [0-24]md) Within 0-24 hours Post Dose on Day 14 (13d)
Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Multiple dose: Pre-dose and 4, 8, 12 and 24 hours post-dose on 13day
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Reticulocytes (Absolute) Within Day 1 (0d) - Day 14 (13d)
Measured: Day 1 to Day 14
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Reticulocytes ( Ratio-to-Baseline-Adjusted) Within Day 1(0d) - Day 14 (13d)
Measured: Day 1 to Day 14
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Hemoglobin (Absolute) Within Day 1 (0d) - Day 14 (13d)
Measured: Day 1 to Day 14
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Hemoglobin ( Ratio-to-Baseline-Adjusted) Within Day 1 (0d) - Day
Measured: Day 1 to Day 14
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Hematocrit (Absolute) Within Day 1 (0d) - Day 14(13d)
Measured: Day 1 to Day 14
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Hematocrit (Ratio-to-Baseline-Adjusted) Within Day 1( 0d) - Day 14 (13d)
Measured: Day 1 to Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2011 (estimated)
- Study startApr 2011
- Primary completionMay 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnemiaStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01332942
- Sponsor's protocol ID
- 14627
- Other IDs
- 2010-023585-50
- Status last verified
- Jul 2015
- First submitted
- 8 Apr 2011
- Last updated
- 14 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Single-blind, Placebo-controlled, Combined Single / Multiple Dose Escalation, Group Comparison Study to Investigate Safety, Tolerability, Pharmacodynamic Effect and Pharmacokinetics of BAY 85-3934 in Patients With Renal Anemia Due to CKD (Stages 3 and 4)
- ClinicalTrials.gov ID
- NCT01332942
- Acronym / sponsor ID
- 14627
- Conditions
- Anemia
- Keywords
- Anemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- Apr 2011
- Primary completion
- May 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 11 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The drug that is under investigation during this study is BAY85-3934 which is intended to be used as a treatment for patients suffering from renal anemia due to chronic kidney disease (stage 3 and 4).
The purpose of this study is to provide safety and tolerability information on the drug. Other objectives of the study are to investigate the effect of the drug on the body (pharmacodynamics) as well as the absorption, breakdown, metabolism, distribution and excretion (pharmacokinetics) by measuring the concentration in blood and urine.
The study will be conducted in one study center in the United Kingdom and several centers in Germany. 84 (of which 36 are optional) patients who meet the inclusion criteria will participate in the study. BAY 85-3934 will be given following a combined single / multiple dose escalation design in seven (of which three are optional) dose steps.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: BAY85-3934 |
| Molidustat (BAY85-3934) 5 mg | Experimental | Drug: BAY85-3934 |
| Molidustat (BAY85-3934) 10 mg | Experimental | Drug: BAY85-3934 |
| Molidustat (BAY85-3934) 25 mg | Experimental | Drug: BAY85-3934 |
| Molidustat (BAY85-3934) 50 mg | Experimental | Drug: BAY85-3934 |
| Molidustat (BAY85-3934) 75 mg | Experimental | Drug: BAY85-3934 |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- The informed consent must be signed before any study specific tests or procedures are done
- Renal anemia due to CKD (stage 3 and 4) not on dialysis assessed by medical history and Creatine Clearance (CLCR) between 15 to 59 mL/min ± 10 % (ie CLCR between 13 - 65 mL/min) estimated at the pre-study visit from the creatinine concentration measured in serum (Modification of Diet in Renal Disease (MDRD) formula)
- Stable renal disease, ie without major changes in therapy within the last 6 weeks and not expected to begin dialysis within the study.
- Female subjects with no child-bearing potential (postmenopausal women with 12 month of spontaneous amenorrhea or with 6 month of spontaneous amenorrhea and serum FSH levels > 30 mIU/mL, women with 6 weeks post bilateral ovariectomy, woman with bilateral tubal ligation, and women with hysterectomy).
- Male subjects who agree to use two forms of effective contraception during the study and for 12 weeks after receiving the study drug. This must include a condom with spermicide gel for 21 days after drug administration.
Key exclusion criteria (26 listed)
- Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal
- Known hypersensitivity to the study drugs (active substances or excipients of the preparations)
- Known severe allergies, non-allergic drug reactions, or multiple drug allergies
- Patients with impaired liver function (Child Pugh B and C based on medical history)
- Patients with hemolysis/hemolytic anemia or active bleeding/blood loss
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAY85-3934Subjects received an oral single dose of placebo tablet matched to the molidustat dose (BAY85-3934) on Day 1 followed by a washout day and once daily multipledose over 12 days (from Day 3 to Day 14). | Drug | Placebo |
| BAY85-3934Subjects received an oral single dose of 5 mg of molidustat IR tablet on Day 1 followed by a washout day and once daily multiple-dose over 12 days (from Day 3 to Day 14). | Drug | Molidustat (BAY85-3934) 5 mg |
| BAY85-3934Subjects received an oral single dose of 10 mg of molidustat ( 2x 5mg IR tablets) on Day 1 followed by a washout day and once daily multipledose over 12 days (from Day 3 to Day 14). | Drug | Molidustat (BAY85-3934) 10 mg |
| BAY85-3934Subjects received an oral single dose of 25 mg of molidustat (1 x 20 mg IR tablet and 1 x 5 mg IR tablet) on Day 1 followed by a washout day and once daily multiple-dose over 12 days (from Day 3 to Day 14). | Drug | Molidustat (BAY85-3934) 25 mg |
| BAY85-3934Subjects received an oral single dose of 50 mg) of molidustat (2 x 20 mg IR tablets and 2 x 5 mg IR tablets) on Day 1 followed by a washout day and once daily multiple-dose over 12 days (from Day 3 to Day 14). | Drug | Molidustat (BAY85-3934) 50 mg |
| BAY85-3934Subjects received an oral single dose of 75 mg of molidustat (3 x 20 mg IR tablets and 3 x 5 mg IR tablets) on Day 1 followed by a washout day and once daily multiple-dose over 12 days (from Day 3 to Day 14). | Drug | Molidustat (BAY85-3934) 75 mg |
Primary outcome
Number of Subjects with Treatment-Emergent Adverse Events (TEAE)
Time frame: From start of study drug administration until last follow-up visit (14 days after the last study drug administration)
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important serious event. TEAEs were defined as AEs/SAEs that started or worsened after the study drug treatment.
Mean Change in Heart Rate Within 4 hours Post-dose
Time frame: Within 4 hours from after administration of study drug on Day 1 and Day 14
Heart rate was observed in all treatment groups in supine position.
Mean Change in Heart Rate Over 1 Minute for Doses 25, 50, 75 Milligrams
Time frame: From start of study drug administration until 12 hours after the last study drug administration
Heart rate was assessed over 1 minute from the Electrocardiogram (ECG) recording.
Mean Change in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Within 4 hours Post-dose
Time frame: Within 4 hours post-dose at Day 1 and Day 14
SBP, DBP was observed in all treatment groups in supine phase.
Number of Subjects with Clinically Relevant Abnormal Findings in the Electrocardiogram (ECG)
Time frame: Day 1 and Day 14
Electrocardiograms were recorded and analyzed by an electronic ECG reading system.
Number of Subjects with Clinically Relevant Laboratory Values
Time frame: Day 1 and Day 14
Laboratory parameters include hematology, coagulation, serum chemistry, urinalysis.
Maximum Observed Drug Concentration (Cmax) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
Cmax refers to the highest measured drug concentration after a single dose which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Maximum Observed Drug Concentration Divided by Dose (Cmax/D) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
Cmax/D is defined as maximum observed drug concentration divided by dose. Cmax refers to the highest measured drug concentration after single dose which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
AUC is a measure of systemic drug exposure after single dose, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC is defined as area under concentration versus time curve from time 0 (pre-dose) to extrapolated infinite time. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Area Under the Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
AUC is a measure of systemic drug exposure after single dose, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC is defined as area under concentration versus time curve from time 0 (pre-dose) to extrapolated infinite time. AUC/D is defined as area under the concentration versus time curve from zero to infinity divided by dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Maximum Observed Drug Concentration (Cmax,md) in Plasma of Molidustat and its Metabolite After Multiple Dose Administration of Molidustat
Time frame: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Cmax,md defined as maximum observed drug concentration after multiple dose. Cmax,md refers to the highest measured drug concentration in the dosing interval which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Maximum Observed Drug Concentration in Plasma Divided by Dose (Cmax,md/D) of Molidustat and its Metabolite After Multiple Dose Administration of Molidustat
Time frame: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Cmax,md/D is defined as maximum observed drug concentration divided by dose after multiple dose administration. Cmax,md refers to the highest measured drug concentration within the dosing interval which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Area Under the Concentration Versus Time Curve From 0 to 24 hour (AUC[0-24]md) in Plasma During any Dose Interval of Molidustat and its Metabolite After Multiple Dose of Molidustat
Time frame: Multiple dose: 0-24 hours post dose on Day 14 (13d)
AUC(0-24)md is defined as area under the concentration versus time curve from 0 to 24 hour after multiple dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Area Under the Concentration Versus Time Curve From 0 to 24 hour Divided by Dose (AUC[0-24] md/D) in Plasma During any Dose Interval of Molidustat and its Metabolite After Multiple Dose of Molidustat
Time frame: Multiple dose: 0-24 hours post dose on Day 14 (13d)
AUC(0-24)md/D is defined as area under the concentration versus time curve from 0 to 24 hour divided by dose after multiple dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
30 secondary outcomes
Maximum Observed Drug Concentration in Plasma Divided by Dose per Kilogram Body Weight (Cmax,norm) of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
Area Under the Concentration Versus Time Curve From Zero to Infinity in Plasma Divided by Dose per Kilogram Body Weight (AUCnorm) of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
Area Under the Concentration Versus Time Curve From Zero to 24 hour (AUC[0-24]) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-24 hours post-dose
Area Under the Concentration Versus Time Curve From Zero to the Last Data Point Above the Lower Limit of Quantification (AUC[0-tlast]) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
Half Life Associated With the Terminal Slope (t1/2) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
Time to Reach Maximum Drug Concentration (tmax) in Plasma of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
Mean Residence Time (MRT) of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
Apparent Oral Clearance (CL/F) of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
Apparent Volume of Distribution During Terminal Phase (Vz/F) After Single Dose of Molidustat
Time frame: Single dose: 0-48 hours post-dose
Amount Excreted into Urine (Aeur) of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Urine collection intervals: 0d00 - 0d12h, 0d12h - 1d00
Renal Body Clearance of Drug (CLR) of Molidustat and its Metabolite After Single Dose of Molidustat
Time frame: Urine collection interval: 0d00 - 1d00
Maximum Observed Concentration Divided by Dose per Kilogram Body Weight (Cmax,md,norm) in Plasma After Multiple Dose Administration During a Dosage Interval
Time frame: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Area Under the Concentration Versus Time Curve From 0 to 24 hour Divided by Dose per Kilogram Body Weight (AUC[0-24]md,norm) in Plasma After Multiple Dose Administration During a Dosage Interval
Time frame: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Half Life Associated With the Terminal Slope (t1/2,md) in Plasma of Molidustat and its Metabolite After Multiple Dose of Molidustat
Time frame: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Time to Reach Maximum Drug Concentration (tmax,md) in Plasma of Molidustat and its Metabolite After Multiple Dose of Molidustat
Time frame: Multiple dose: 0-24 hours post dose on Day 14 (13d)
Amount Excreted into Urine (Aeur,md)of Molidustat and its Metabolite After Multiple Dose of Molidustat
Time frame: Urine collection interval: 13d00 - 14d00
Renal Body Clearance (CLR,md) of Molidustat and its Metabolite After Multiple Dose of Molidustat
Time frame: Urine collection interval: 13d00 - 14d00
Accumulation Ratio of AUC in the Dosing Interval (RAAUC) of Molidustat
Time frame: All samples from 0-24h on 0d and from 0-24h on 13d
Accumulation Ratio of Cmax (RACmax) of Molidustat
Time frame: All samples from 0-24h on 0d and from 0-24h on 13d
Linearity Factor of Pharmacokinetics After Repeated Administration of Identical Doses (RLin) of Molidustat
Time frame: All samples from 0-24h on 0d and from 0-24h on 13d
Erythropoietin Concentration: Area Under the Concentration Versus Time Curve From 0 to 24 hour (AUC[0-24]) Post-dose on Day 1 (0d)
Time frame: Single dose: Pre-dose and 4, 8, 12 and 24 hours post-dose
Erythropoietin Concentration: Area Under the Concentration Versus Time Curve From 0 to 24 hour (AUC[0-24]md) in Plasma After Multiple Dose on Day 14 (13d)
Time frame: Multiple dose: Pre-dose and 4, 8, 12 and 24 hours post-dose on 13day
Erythropoietin Concentration: Maximum Observed Drug Concentration in Plasma (Cmax[0-24]) After Single Dose of Molidustat on Day 1 (0d)
Time frame: Single dose: Pre-dose and 4, 8, 12, 24 hours post-dose
Erythropoietin Concentration: Maximum Observed Drug Concentration in Plasma (Cmax [0-24]md) Within 0-24 hours Post Dose on Day 14 (13d)
Time frame: Multiple dose: Pre-dose and 4, 8, 12 and 24 hours post-dose on 13day
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Reticulocytes (Absolute) Within Day 1 (0d) - Day 14 (13d)
Time frame: Day 1 to Day 14
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Reticulocytes ( Ratio-to-Baseline-Adjusted) Within Day 1(0d) - Day 14 (13d)
Time frame: Day 1 to Day 14
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Hemoglobin (Absolute) Within Day 1 (0d) - Day 14 (13d)
Time frame: Day 1 to Day 14
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Hemoglobin ( Ratio-to-Baseline-Adjusted) Within Day 1 (0d) - Day
Time frame: Day 1 to Day 14
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Hematocrit (Absolute) Within Day 1 (0d) - Day 14(13d)
Time frame: Day 1 to Day 14
Pharmacodynamic Parameter: Maximum Observed Drug Concentration in Plasma (Cmax) of Hematocrit (Ratio-to-Baseline-Adjusted) Within Day 1( 0d) - Day 14 (13d)
Time frame: Day 1 to Day 14
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2015.
- Click here to find information about studies related to Bayer Healthcare products conducted in EuropeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BAY85-3934 in people with Anemia, run by Bayer at 11 sites in 2 countries.
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 10 inclusion and 26 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 14 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Germany, United Kingdom. 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. Some participants in this study may receive a placebo. 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 Subjects with Treatment-Emergent Adverse Events (TEAE) (time frame: From start of study drug administration until last follow-up visit (14 days after the last study drug administration)). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jul 2015.