To Investigate Pharmacokinetics (Absorption, Distribution, Elimination), Safety and Tolerability of a Single Oral Dose of 75 mg Molidustat Tablet in Male and Female Subjects Requiring Hemo- or Peritoneal Dialysis Compared to Healthy Subjects

Investigation of Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Single Oral Doses of 75 mg Molidustat in Male and Female Subjects With Renal Impairment Requiring Hemo- or Peritoneal Dialysis Compared to Age- and Weight-matched Healthy Subjects in a Single-center, Non-controlled, Non-blinded Study With Group Stratification

The study investigates the pharmacokinetics (absorption, distribution, elimination) of molidustat after intake of a single 75 mg tablet in subjects with renal impairment requiring hemo- or peritoneal dialysis compared to age-and gender-matched healthy subjects. In addition, the effect of molidustat on the hormone erythropoietin will be evaluated as well as the safety and tolerability of molidustat.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency, Chronic
• Intervention / Treatment: Drug: Molidustat(BAY85-3934); Drug: Molidustat(BAY85-3934)

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Nordrhein-Westfalen
    • Velbert, Nordrhein-Westfalen, Germany, 42549
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female (without childbearing potential)
• Age: ≥18 and ≤79 years of age
• Body mass index (BMI): ≥18 and ≤34 kg/m2
• Ethnicity: White
• Subjects with severe renal impairment on hemodialysis or peritoneal dialysis, and
• Healthy subjects

Exclusion Criteria:

• Women of childbearing potential, pregnant or lactating women
• Use of medication within the 2 weeks preceding the study which could interfere with the investigational product
• Positive results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (HCV Ab), human immune deficiency virus 1 and 2 antibodies (HIV 1/2 Ab)
• Exclusion periods from other studies or simultaneous participation in other clinical studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Single oral dose of 75 mg molidustat (fasted) in subjects on hemodialysis (at start of hemodialysis and on a hemodialysis free day,respectively)	Drug: Molidustat(BAY85-3934); Two single oral doses of 75 mg molidustat tablet in subjects on hemodialysis and peritoneal dialysis; Drug: Molidustat(BAY85-3934); One single oral dose of 75 mg molidustat in healthy subjects
Experimental: Arm 2; Single oral dose of 75 mg molidustat (fasted) in subjects on peritoneal dialysis (after start of peritoneal dialysis intervall and, optionally, after the start of a peritoneal dialysis-free intervall,respectively)	Drug: Molidustat(BAY85-3934); Two single oral doses of 75 mg molidustat tablet in subjects on hemodialysis and peritoneal dialysis; Drug: Molidustat(BAY85-3934); One single oral dose of 75 mg molidustat in healthy subjects
Experimental: Arm 3; Single oral dose of 75 mg molidustat (fasted) in healthy subjects	Drug: Molidustat(BAY85-3934); Two single oral doses of 75 mg molidustat tablet in subjects on hemodialysis and peritoneal dialysis; Drug: Molidustat(BAY85-3934); One single oral dose of 75 mg molidustat in healthy subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics characterized by Cmax of Molidustat	Cmax: maximum drug concentration in plasma after single dose administration	Up to 96 hours post dose
Pharmacokinetics characterized by AUC of Molidustat	AUC: area under the plasma concentration vs time curve from zero to infinity	Up to 96 hours post dose
Pharmacokinetics characterized by Cmax,norm of Molidustat	Cmax,norm;maximum drug concentration in plasma after single dose administration divided by dose (milligrams) per kilogram body weight	Up to 96 hours post dose
Pharmacokinetics characterized by (AUCnorm) of Molidustat	AUCnorm; area under the plasma concentration vs time curve divided by dose per kg body weight	Up to 96 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics characterized by Cmax of erythropoietin	Cmax: maximum drug concentration in plasma after single dose administration	Up to 48 hours post dose
Pharmacokinetics characterized by AUC (0-tlast) of erythropoietin	AUC(0-tlast): AUC from time 0 to the last data point above lower limit of quantification	Up to 48 hours post dose
Pharmacokinetics characterized by tmax of erythropoietin	tmax: time to reach maximum drug concentration in plasma after single (first) dose	Up to 48 hours post dose
Number of subjects with Treatment Emergent Adverse Event (TEAE)		Up to 7 days post dose

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2015
• Primary Completion (Actual): December 2, 2015
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: December 5, 2014
• First Submitted That Met QC Criteria: December 5, 2014
• First Posted (Estimate): December 9, 2014

Study Record Updates

• Last Update Posted (Actual): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 22, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Erythropoietin; Pharmacokinetics; Chronic kidney disease; Hemodialysis; Peritoneal dialysis
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
• Other Study ID Numbers: 17767; 2014-003292-31 (EudraCT Number)