Combined Single / Multiple Dose Escalation Study in Patie... | NCT01332942

ID	Type	Description	Link
2010-023585-50	EudraCT Number

Status Module

Description Module

Label	Type	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
BAY85-3934	Drug	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).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	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.	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.	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.	Day 1 and Day 14

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.
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

Exclusion Criteria:

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
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

Facility	Status	City	State	ZIP	Country	Contacts
		München	Bavaria	81241	Germany

ID	Term
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases