Combined Single / Multiple Dose Escalation Study in Patients With Renal Anemia Due to CKD (Chronic Kidney Disease)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01332942
First received: April 8, 2011
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Anemia
Drug: BAY85-3934
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
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)

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Adverse Event reporting [ Time Frame: Up to 14 days after last dosing ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Plasma concentration AUC of BAY85-3934 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • Plasma concentration Cmax of BAY85-3934 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • Erythropoietin concentration [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: April 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: BAY85-3934
total dose given over 13 days: 65 mg BAY85-3934 or equivalent placebo
Experimental: Arm 2 Drug: BAY85-3934
total dose given over 13 days: 130 mg BAY85-3934 or equivalent placebo
Experimental: Arm 3 Drug: BAY85-3934
total dose given over 13 days: 325 mg BAY85-3934 or equivalent placebo
Experimental: Arm 4 Drug: BAY85-3934
total dose given over 13 days: 650 mg BAY85-3934 or equivalent placebo
Experimental: Arm 5 Drug: BAY85-3934
total dose given over 13 days: 973 mg BAY 85-3934 (optional) or equivalent placebo
Experimental: Arm 6 Drug: BAY85-3934
total dose given over 13 days:1300 mg BAY85-3934 (optional) or equivalent placebo
Experimental: Arm 7 Drug: BAY85-3934
total dose given over 13 days: 1625 mg BAY 85-3934 (optional) or equivalent placebo

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01332942

Locations
Germany
München, Bayern, Germany, 81241
Hannover, Niedersachsen, Germany, 30159
Hannover, Niedersachsen, Germany, 30625
Düsseldorf, Nordrhein-Westfalen, Germany, 40225
Köln, Nordrhein-Westfalen, Germany, 50931
Kiel, Schleswig-Holstein, Germany, 24105
Berlin, Germany, 10117
Berlin, Germany, 13125
Hamburg, Germany, 20253
Wuppertal, Germany, 42283
United Kingdom
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01332942     History of Changes
Other Study ID Numbers: 14627, 2010-023585-50
Study First Received: April 8, 2011
Last Updated: July 7, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Federal Institute for Drugs and Medical Devices (BfArM)

Keywords provided by Bayer:
Anemia

Additional relevant MeSH terms:
Anemia
Hematologic Diseases

ClinicalTrials.gov processed this record on October 21, 2014