A Study of Molidustat for Treatment of Renal Anemia in Peritoneal Dialysis Subjects (MIYABI PD)

An Open-label, Multicenter Study to Investigate the Efficacy and Safety of Oral Molidustat in Peritoneal Dialysis Subjects With Renal Anemia

The purpose of this study is to evaluate the efficacy and safety of molidustat in peritoneal dialysis subjects with renal anemia

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukui, Japan, 918-8503
    • Fukui-ken Saiseikai Hospital
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Fukuoka, Japan, 815-8555
    • Japanese Red Cross Fukuoka Hospital
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Gifu, Japan, 500-8523
    • Asahi University Hospital
  • Kyoto, Japan, 612-8555
    • National Hospital Organization Kyoto Medical Center
  • Nara, Japan, 630-8581
    • Nara Prefecture General Medical Center
  • Niigata, Japan, 950-1197
    • Niigata City General Hospital
  • Oita, Japan, 870-0033
    • Japanese Red Cross Oita Hospital
  • Osaka, Japan, 558-8558
    • Osaka General Medical Center
  • Aichi
    • Yatomi, Aichi, Japan, 498-8502
      • Kainan Hospital
  • Ehime
    • Matsuyama, Ehime, Japan, 790-0024
      • Ehime Prefectural Central Hospital
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 802-8555
      • Kokura Memorial Hospital
    • Kitakyushu, Fukuoka, Japan, 806-8501
      • JCHO Kyushu Hospital
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0814
      • Elm Grove Clinic
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Kanagawa
    • Fujisawa, Kanagawa, Japan, 251-8550
      • Fujisawa City Hospital
    • Kamakura, Kanagawa, Japan, 247-8533
      • Shonan Kamakura General Hospital
    • Kawasaki, Kanagawa, Japan, 213-8587
      • Toranomon Hospital Kajigaya
    • Yokohama, Kanagawa, Japan, 227-8501
      • Showa University Fujigaoka Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 983-8512
      • Tohoku Medical and Pharmaceutical University Hospital
  • Niigata
    • Shibata, Niigata, Japan, 957-8588
      • Niigata Prefectural Shibata Hospital
  • Oita
    • Beppu, Oita, Japan, 874-0011
      • National Hospital Organization Beppu Medical Center
  • Okinawa
    • Uruma, Okinawa, Japan, 904-2293
      • Okinawa prefectural Chubu Hospital
  • Osaka
    • Izumi, Osaka, Japan, 594-0076
      • Fuchu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject with end-stage kidney disease (ESKD) on peritoneal dialysis prior to assignment and not expected to start maintenance dialysis (e.g., hemodialysis, hemodiafiltration) other than peritoneal dialysis during the study period
• Body weight > 40 and ≤ 160 kg at screening
• Male or female subject ≥ 20 years of age at screening
• At least one kidney

• Subjects who meet one of the 1 or 2 following criteria

  • Subjects untreated with ESA at assignment: Mean of the last 2 Hb level (central laboratory measurement) during the screening period must be ≥ 8.0 and < 11.0 g/dL (2 measurements must be taken ≥ 2 days apart and the difference between the 2 measurements must be < 1.2 g/dL) with the last screening Hb measurement within 14 days prior to study drug assignment
  • Subjects pre treated with ESA at assignment: Mean of the last 2 Hb level (central laboratory measurement) during the screening period must be ≥ 10.0 and < 13.0 g/dL (2 measurements must be taken ≥ 2 days apart and the difference between the 2 measurements must be < 1.2 g/dL) with the last screening Hb measurement within 14 days prior to study drug assignment

• Subjects who meet one of the 1 or 2 following criteria

  • Subjects untreated with ESA at assignment: Subject with ESKD on peritoneal dialysis for at least 2 weeks prior to assignment. AND. Subject not received ESA for 8 weeks prior to assignment. OR. In case of the patient washed out from ESAs, when mean of the last 2 Hb level (at least 2 central laboratory measurements must be taken ≥ 2 days apart) has decrease to ≥ 0.5g/dL from the Hb level (central laboratory measurement) after the last ESA administration, AND the interval from the last ESA administration to the study drug assignment should be over 2 week for epoetin-alpha/beta, 4 weeks for darbepoetin alpha or epoetin beta pegol

  • Subjects pre treated with ESA at assignment:

    • Subject with ESKD on peritoneal dialysis for at least 12 weeks prior to assignment
    • Subject treated with ESA by IV or SC within 8 weeks prior to assignment
    • Treated with 2 or 4 weekly dose of darbepoetin alfa, 4 weekly dose of epoetin beta pegol, OR 3 times per week, twice per week, weekly or bi-weekly dose of epoetin alfa/beta, and having had no more than one dose change within 8 weeks prior to assignment

Exclusion Criteria:

• New York Heart Association (NYHA) Class III or IV congestive heart failure
• History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, pulmonary thromboembolism, and acute limb ischemia) within 6 months prior to randomization
• Sustained and poorly controlled arterial hypertension (defined as systolic BP≥ 180mmHg or diastolic BP ≥ 110mmHg) or hypotension (defined as systolic BP < 90mmHg) at randomization
• Proliferative choroidal or retinal disease, such as neovascular age-related macular degeneration or proliferative diabetic retinopathy requiring invasive treatment (e.g., intraocular injections or laser photocoagulation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Molidustat (BAY85-3934); Molidustat group	Drug: Molidustat (BAY85-3934); Starting dose of molidustat once daily (OD) will be titrated based on the subject's Hb (Hemoglobin) response

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder rate: proportion of responders among the subjects	Responder is defined as meeting all of the following criteria: (i) Mean of the Hb levels in the target range (ii) ≥ 50% of the Hb levels in the target range (iii) No rescue treatment	Week 30 to 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of rise in Hb (Hemoglobin) level (g/dL/week)		Up to 8 weeks
Rate of rise in Hb (Hemoglobin) level (g/dL/week)		Up to 4 weeks
Mean Hb (Hemoglobin) level		Week 30 to 36
Change in mean Hb level		Baseline and Week 30 to 36
Proportion of subjects who meet each component of the response	Response: (i) Mean of the Hb levels in the target range (ii) ≥ 50% of the Hb levels in the target range (iii) No rescue treatment	Week 30 to 36
Hb level		Baseline and Up to Week 36
Change in Hb level		Baseline and Up to Week 36
Proportion of subjects with mean hemoglobin levels are in the target range		Week 30 to 36
Proportion of subjects with mean hemoglobin levels are above the target range		Week 30 to 36
Proportion of subjects with mean hemoglobin levels are below the target range		Week 30 to 36
Proportion of subjects with hemoglobin levels in the target range		Up to 36 weeks
Proportion of subjects with hemoglobin levels above the target range		Up to 36 weeks
Proportion of subjects with hemoglobin levels below the target range		Up to 36 weeks
Proportion of subjects whose maximum rise in Hb between each consecutive visits is above 0.5 g/dL/week	Defined as change in Hb level / duration between two visits (weeks)	Up to 36 weeks
Percentage of days in the target Hb range during the evaluation period		Week 30 to 36
Percentage of days in the target Hb range during the treatment period		Up to 36 weeks
Rate of rise in Hb level (g/dL/week) between each consecutive visits		Up to 36 weeks
Percentage of Hb levels in target range during the evaluation period	Defined as the number of measurements in the target range / number of measurements x 100 [%])	Week 30 to 36
Percentage of Hb levels in target range during the treatment period	Defined as the number of measurements in the target range / number of measurements x 100 [%])	Up to 36 weeks
Proportion of subjects who received at least one rescue treatment		Up to 36 weeks
Proportion of subjects whose Hb level was ≥ 13.0 g/dL or < 8.0 g/dL		Up to 36 weeks
Number of participants with serious adverse events		Up to 36 weeks
Maximum concentration (Cmax) of Molidustat		Baseline, Week 8, Wee16 and Week 36
Area under the concentration-time curve (AUC) of Molidustat		Baseline, Week 8, Wee16 and Week 36
EPO (Erythropoietin) serum concentration of Molidustat		Baseline, Week 8, Wee16 and Week 36

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Akizawa T, Taguchi M, Matsuda Y, Iekushi K, Yamada T, Yamamoto H. Molidustat for the treatment of renal anaemia in patients with dialysis-dependent chronic kidney disease: design and rationale of three phase III studies. BMJ Open. 2019 Jun 14;9(6):e026602. doi: 10.1136/bmjopen-2018-026602.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2018
• Primary Completion (Actual): July 25, 2019
• Study Completion (Actual): July 29, 2019

Study Registration Dates

• First Submitted: January 26, 2018
• First Submitted That Met QC Criteria: January 26, 2018
• First Posted (Actual): February 1, 2018

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Hematologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Anemia
• Other Study ID Numbers: 19353

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No