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

NCT01679587 | Completed Phase 1

• 2 other identifiers: 163702012-002375-33
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 3

Brief 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, 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

Outcome Measures

Primary Outcomes (10)

• Number of participants with adverse events

  Approximately 9 weeks

• Blood pressure

  Systolic, diastolic, mean blood pressure

  Approximately 9 weeks

• Heart rate

  Approximately 9 weeks

• Cmax

  Maximum observed drug concentration in measured matrix after single dose administration

  Pre-dose and up to 48 h post-dose

• Cmax/D

  Cmax divided by dose

  Pre-dose and up to 48 h post-dose

• AUC

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

  Pre-dose and up to 48 h post-dose

• AUC/D

  AUC divided by dose

  Pre-dose and up to 48 h post-dose

• Heart rate over 1 min

  Pre-dose and up to 24 h post-dose

• Standing blood pressure procedure

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

• Impedance cardiography

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

  Pre-dose and up tp 8 h post-dose

Secondary Outcomes (18)

• Change of hematology profile

  From baseline to Day 1 after single dose

• Cmax,norm

  Pre-dose and up to 48 h post-dose

• AUCnorm

  Pre-dose and up to 48 h post-dose

• AUC(0-24)

  Pre-dose and up to 24 h post-dose

• AUC(0-tlast)

  Pre-dose and up to 48 h post-dose

Study Arms (4)

Molidustat, 80 mg

EXPERIMENTAL

Subjects 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.

Drug: Molidustat (BAY85-3934); Drug: Placebo

Molidustat, 120 mg

EXPERIMENTAL

Subjects 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.

Drug: Molidustat (BAY85-3934); Drug: Placebo

Molidustat, 40 mg

EXPERIMENTAL

Subjects 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.

Drug: Molidustat (BAY85-3934); Drug: Placebo

Molidustat, 160 mg

EXPERIMENTAL

Subjects 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.

Drug: Molidustat (BAY85-3934); Drug: Placebo

Interventions

Molidustat (BAY85-3934) DRUG

20 mg molidustat as a single tablet

Molidustat, 120 mg; Molidustat, 160 mg; Molidustat, 40 mg; Molidustat, 80 mg

Placebo DRUG

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

Molidustat, 120 mg; Molidustat, 160 mg; Molidustat, 40 mg; Molidustat, 80 mg

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (3)

Unknown Facility

München, Bavaria, 81241, Germany

Location

Unknown Facility

Mönchengladbach, North Rhine-Westphalia, 41061, Germany

Location

Unknown Facility

Kiel, Schleswig-Holstein, 24105, Germany

Location

Related Publications (1)

• 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.

  PMID: 36005278 DERIVED

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

MeSH Terms

Conditions

Kidney Diseases

Interventions

molidustat

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2012
• First Posted: September 6, 2012
• Study Start: September 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: July 1, 2013
• Last Updated: May 2, 2016

Record last verified: 2016-04

Locations

DE (3)