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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01679587
First received: September 3, 2012
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

The phase I study will investigate the hemodynamic effects as well as safety, tolerability, and pharmacokinetics of BAY 85-3934 in patients with chronic kidney disease (CKD).

For hemodynamic evaluation blood pressure, heart rate and cardiac output will be measured. Blood samples will be taken for safety laboratory, the measurement of BAY 85-3934 concentrations and biomarkers.

A maximum of 4 dose-escalation steps are planned. Each dose step consists of 2 study periods which are separated by a wash-out period of at least 1 week. Subjects will receive in a cross-over design a single dose of either active drug or placebo in these periods according to randomization. The planned dose steps are single oral doses of 80, 120mg and optionally 40 and/ or 160 mg given as tablets.


Condition Intervention Phase
Kidney Diseases
Drug: BAY85-3934
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
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 BAY85 3934 in Subjects With Chronic Kidney Disease (CKD)

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Number of participants with adverse events as a measure of safety and tolerability of BAY85-3934 [ Time Frame: Up to 30 days after last dosing ] [ Designated as safety issue: Yes ]
  • Blood pressure (systolic, diastolic, mean) [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
  • Hemodynamic assessment [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    non-invasive stroke volume and cardiac output

  • Heart rate and heart rate over 1 min [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic profile determined by plasma concentration of BAY85-3934 [ Time Frame: 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h,36 h, 48 h post dose ] [ Designated as safety issue: No ]
  • Change of hematology profile [ Time Frame: From baseline to Day 1 after single dose ] [ Designated as safety issue: No ]
    Hematology profile includes blood concentration of erythropoietin, reticulocytes, erythrocytes, hemoglobin, hematocrit, and exploratory biomarkers.

  • Number of subjects with abnormal Electrocardiogram (ECG) measured by QTcBazett > 500 msec [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Number of subjects with clinically relevant laboratory deviations. [ Time Frame: Up to Day 3 ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: September 2012
Study Completion Date: July 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Subjects will receive a single oral dose of 80 mg BAY85-3934 in the first period and placebo in the second period, separated by a wash-out period of at least 1 week.
Drug: BAY85-3934
Four escalated single oral dose steps of BAY85-3934 will be given - step 1 - 40mg (optional), step 2 - 80mg; step 3 - 120mg step 4 - 160mg (optional). Per arm one dose step will be conducted.
Drug: Placebo
Single oral dose of matching placebo will be given in each treatment step
Experimental: Arm 2
Subjects will receive a single oral dose of 120 mg BAY85-3934 in the first period and placebo in the second period, separated by a wash-out period of at least 1 week.
Drug: BAY85-3934
Four escalated single oral dose steps of BAY85-3934 will be given - step 1 - 40mg (optional), step 2 - 80mg; step 3 - 120mg step 4 - 160mg (optional). Per arm one dose step will be conducted.
Drug: Placebo
Single oral dose of matching placebo will be given in each treatment step
Experimental: Arm 3
Subjects will receive a single oral dose of 40 mg BAY85-3934 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: BAY85-3934
Four escalated single oral dose steps of BAY85-3934 will be given - step 1 - 40mg (optional), step 2 - 80mg; step 3 - 120mg step 4 - 160mg (optional). Per arm one dose step will be conducted.
Drug: Placebo
Single oral dose of matching placebo will be given in each treatment step
Experimental: Arm 4
Subjects will receive a single oral dose of 160 mg BAY85-3934 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: BAY85-3934
Four escalated single oral dose steps of BAY85-3934 will be given - step 1 - 40mg (optional), step 2 - 80mg; step 3 - 120mg step 4 - 160mg (optional). Per arm one dose step will be conducted.
Drug: Placebo
Single oral dose of matching placebo will be given in each treatment step

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01679587

Locations
Germany
München, Bayern, Germany, 81241
Mönchengladbach, Nordrhein-Westfalen, Germany, 41061
Kiel, Schleswig-Holstein, Germany, 24105
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01679587     History of Changes
Other Study ID Numbers: 16370, 2012-002375-33
Study First Received: September 3, 2012
Last Updated: March 6, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency

ClinicalTrials.gov processed this record on August 28, 2014