Long Term Extension Study for the Maintenance Treatment of Anemia Associated With Chronic Kidney Disease (CKD) in Hemodialysis Subjects on Epoetin Alfa / Beta Treatment Versus BAY85-3934 (DIALOGUE5)

A Controlled, Parallel Group, Open-label, Multicenter Extension Study to Investigate Efficacy and Safety of Oral BAY85-3934 and Active Comparator (Epoetin Alfa / Beta) in the Long-term Treatment of Subjects With Anemia Associated With Chronic Kidney Disease Who Are on Dialysis in the United States and Japan

Evaluate efficacy and safety up to 36 months of titrated dose treatment with BAY85-3934 versus epoetin alfa/beta. Titration will be based on the subject's hemoglobin (Hb) response and tolerability of the prior dose. Planned doses include 15, 25, 50, 75, 100,and 150 mg once daily.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 607-8116
  • Hokkaido
    • Muroran, Hokkaido, Japan, 050-0083
  • Mie
    • Kuwana, Mie, Japan, 511-0061
• United States
  • California
    • Azusa, California, United States, 91702
    • Long Beach, California, United States, 90813
    • Lynwood, California, United States, 90262
    • Northridge, California, United States, 91324
    • San Dimas, California, United States, 91773
    • Whittier, California, United States, 90606
    • Whittier, California, United States, 90602
  • Florida
    • New Port Richey, Florida, United States, 34652
    • Pembroke Pines, Florida, United States, 33028
  • Michigan
    • Detroit, Michigan, United States, 48202
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
  • New York
    • Buffalo, New York, United States, 14215
  • Ohio
    • Cincinnati, Ohio, United States, 45206
    • Toledo, Ohio, United States, 43615
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
  • Tennessee
    • Nashville, Tennessee, United States, 37212-8150
  • Texas
    • Fort Worth, Texas, United States, 76104
    • Fort Worth, Texas, United States, 76105
    • Fort Worth, Texas, United States, 76164
    • Grand Prairie, Texas, United States, 75050
    • Houston, Texas, United States, 77004
    • Houston, Texas, United States, 77091
    • Mansfield, Texas, United States, 76063

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eligible male or female subjects were previously enrolled in Study 16208, have a diagnosis of anemia associated with CKD, and are on hemodialysis.
• Men who agree to use adequate contraception when sexually active or women without childbearing potential
• Participation and completion of treatment in Study 16208; subjects must have received 16 weeks of study medication and completed the end of treatment visit (Day 113) in the parent study
• Mean Hb concentration of 9.5 to 11.5 g/dL, inclusive, during the evaluation period (i.e., the last 4 weeks of the parent study) when the subject completed 16 weeks of treatment with BAY85-3934, epoetin alfa, or epoetin beta in Study 16208

Exclusion Criteria:

• A scheduled kidney transplant or any other organ transplant within the next 6 months (being on a waiting list does not exclude the subject)
• Updates to medical and surgical history which meet the exclusion criteria in the parent study
• Subjects treated with immunosuppressive therapy and the breast cancer resistant protein (BCRP) substrates, irinotecan, topotecan, methotrexate, imatinib, and lapatinib
• Sustained, poorly controlled arterial hypertension or hypotension at baseline, defined as mean BP ≥ 180/110 mmHg or systolic BP < 95 mmHg, respectively
• Severe rhythm or conduction disorder (e.g., HR < 50 or > 110 bpm, atrial fibrillation or flutter, prolonged QT > 500 msec, second or third degree atrioventricular [AV] block)
• New York Heart Association Class III or IV congestive heart failure
• Severe hepatic insufficiency (defined as alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma-glutamyl transferase > 3 x the upper limit of norma [ULN], total bilirubin > 2 mg/dL, or Child-Pugh B or C) or active hepatitis in the investigator's opinion
• An ongoing SAE from Study 16208 that is assessed as related to study drug
• Alcohol or drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Molidustat (BAY85-3934)	Drug: Molidustat (BAY85-3934); Subjects will continue with the same treatment they were receiving in the parent study (16208). BAY85-3934 will be administered daily as oral tablets. Dose assessments will be made every 4 (± 1) weeks. At the scheduled visits, the dose may be titrated on an individualized basis taking into account the subject's Hb response and the tolerability of the previous dose. Total treatment time is up to 36 months. Planned doses include 15, 25, 50, 75, 100, and 150 mg once daily.
Active Comparator: Epoetin alfa/beta	Biological: Epoetin alfa/beta; Subjects will continue with the same treatment they were receiving in the parent study (16208). Epoetin alfa / beta will be administered as intravenous (IV) or subcutaneous (SC) injections per individual subject regimen according to the local label. Dose assessments will be made every 4 (± 1) weeks. At the scheduled visits,dose may be titrated on an individualized basis taking into account the subject's Hb response and the tolerability of the previous dose.Total treatment time is up to 36 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in local laboratory hemoglobin level from baseline	Baseline up to 36 months
Number of participants with serious adverse events as a measure of safety and tolerability	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Maintenance in hemoglobin target range (10.0 to 11.0 g/dL)	Up to 36 months
Maintenance in hemoglobin target range (9.5 to 11.5 g/dL)	Up to 36 months
Duration of treatment exposure	Up to 36 months
Number of subjects requiring titration of dose	Up to 36 months
Change of reticulocyte count from baseline of this study	Baseline up to 36 months
Change of reticulocyte count from baseline of study 16208	Baseline up to 36 months
Change of red blood cell count from baseline of this study	Baseline up to 36 months
Change of red blood cell count from baseline of study 16208	Baseline up to 36 months
Change of hematocrit from baseline of this study	Baseline up to 36 months
Change of hematocrit from baseline of study 16208	Baseline up to 36 months
Change of central laboratory hemoglobin level from baseline of this study	Baseline up to 36 months
Change of central laboratory hemoglobin level from baseline of study 16208	Baseline up to 36 months

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2014
• Primary Completion (Actual): October 19, 2016
• Study Completion (Actual): November 16, 2016

Study Registration Dates

• First Submitted: February 14, 2014
• First Submitted That Met QC Criteria: February 14, 2014
• First Posted (Estimate): February 17, 2014

Study Record Updates

• Last Update Posted (Actual): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Anemia of CKD on dialysis
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: 16209