A Study of Molidustat for Maintenance Treatment of Renal Anemia in Non-dialysis Subjects

A Randomized, Open-label, Active-controlled, Parallel-group, Multicenter Study to Investigate the Efficacy and Safety of Oral Molidustat in Comparison to Darbepoetin Alfa in Non-dialysis Subjects Previously Treated With Erythropoiesis-Stimulating Agents (ESAs)

Sponsors

Lead Sponsor: Bayer

Source Bayer
Brief Summary

The purpose of this study is to evaluate the efficacy and safety of molidustat in non-dialysis subjects previously treated with Erythropoiesis-Stimulating Agents (ESAs)

Overall Status Completed
Start Date December 13, 2017
Completion Date November 28, 2019
Primary Completion Date July 5, 2019
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Mean Hb (Hemoglobin) level From week 30 to 36
Change in hemoglobin level from baseline to the average during the evaluation period Baseline and week 30 to 36
Secondary Outcome
Measure Time Frame
Responder rate: proportion of responders among the subjects From week 30 to 36
Proportion of subjects who meet each component of the response From week 30 to 36
Hb level Baseline and up to 52 weeks
Change in Hb level Baseline and up to 52 weeks
Proportion of subjects whose mean hemoglobin levels are in the target range during the evaluation period From week 30 to 36
Proportion of subjects whose mean hemoglobin levels are above the target range during the evaluation period From week 30 to 36
Proportion of subjects whose mean hemoglobin levels are below the target range during the evaluation period From week 30 to 36
Proportion of subjects whose hemoglobin levels are in the target range Up to 52 weeks
Proportion of subjects whose hemoglobin levels are above the target range Up to 52 weeks
Proportion of subjects whose hemoglobin levels are below the target range Up to 52 weeks
Proportion of subjects whose maximum rise in Hb between each consecutive visits is above 0.5 g/dL/week Up to 52 weeks
Number of participants with serious adverse events Up to 52 weeks
Maximum concentration (Cmax) of Molidustat At baseline, week 12, week 24 and week 52
Area under the concentration-time curve (AUC) of Molidustat At baseline, week 12, week 24 and week 52
EPO (Erythropoietin) serum concentration of Molidustat At baseline, week 12, week 24 and week 52
Enrollment 164
Condition
Intervention

Intervention Type: Drug

Intervention Name: Molidustat (BAY85-3934)

Description: Starting dose of 25 mg or 50 mg molidustat once daily (OD) will be titrated based on the subject's Hb response

Arm Group Label: Molidustat (BAY85-3934)

Intervention Type: Drug

Intervention Name: Darbepoetin alfa

Description: Starting dose and frequency of darbepoetin alfa are based on previous ESA. The dose will be titrated based on the subject's Hb response

Arm Group Label: Darbepoetin alfa

Eligibility

Criteria:

Inclusion Criteria:

- Subjects with estimated glomerular filtration rate (eGFR)< 60 mL/min/1.73m^2 (Chronic kidney disease [CKD] stages 3 to 5)

- Have used the same ESA for 8 weeks prior to screening

- Treated with darbepoetin alfa with bi-weekly or monthly dose, epoetin beta pegol with monthly, OR epoetin alfa/beta weekly or bi-weekly, and having had no more than one dose change within 8 weeks prior to randomization

- Body weight > 40 and ≤ 160 kg at screening

- Male or female subject ≥ 20 years of age at screening

- Not on dialysis and not expected to start dialysis during the study period

- Mean screening Hb level ≥ 10.0 and < 13.0 g/dL (mean of all central laboratory Hb levels [at least 2 measurements must be taken ≥ 2 days apart] during the 8-week screening period, AND all Hb level must be measured by the central laboratory, AND the difference between the lowest level and highest level is < 1.2 g/dL), with the last screening Hb level measurement within 14 days prior to randomization

- Ferritin ≥ 100 ng/mL or Transferrin saturation ≥ 20%

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 (blood pressure)≥ 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)

Gender: All

Minimum Age: 20 Years

Maximum Age: N/A

Healthy Volunteers: No

Location
Facility:
Kainan Hospital | Yatomi, Aichi, 498-8502, Japan
Seikeikai New Tokyo Heart Clinic | Matsudo, Chiba, 271-0077, Japan
Ehime Prefectural Central Hospital | Matsuyama, Ehime, 790-0024, Japan
Saiseikai Matsuyama Hospital | Matsuyama, Ehime, 791-8026, Japan
Iizuka Hospital | Iizuka, Fukuoka, 820-8505, Japan
Kokura Memorial Hospital | Kitakyushu, Fukuoka, 802-8555, Japan
Steel Memorial Yawata Hospital | Kitakyushu, Fukuoka, 805-8508, Japan
National Fukuoka-Higashi Medical Center | Koga, Fukuoka, 811-3195, Japan
Kurume University Hospital | Kurume, Fukuoka, 830-0011, Japan
St.Mary's Hospital | Kurume, Fukuoka, 830-8543, Japan
Matsunami Health Promotion Clinic | Hashima-gun, Gifu, 501-6061, Japan
Mazda Hospital of Mazda Motor Corporation | Aki-gun, Hiroshima, 735-8585, Japan
Nippon Kokan Fukuyama Hospital | Fukuyama, Hiroshima, 721-0927, Japan
Higashihiroshima Medical Center | Higashihiroshima, Hiroshima, 739-0041, Japan
Teine Keijinkai Clinic | Sapporo, Hokkaido, 006-8555, Japan
Kobe City Medical Center General Hospital | Kobe, Hyogo, 650-0047, Japan
National Hospital Organization Kobe Medical Center | Kobe, Hyogo, 654-0155, Japan
Mito Kyodo General Hospital | Mito, Ibaraki, 310-0015, Japan
Public Central Hospital of Matto Ishikawa | Hakusan, Ishikawa, 924-8588, Japan
KenAiKai medical corporation Akiyama clinic | Takamatsu, Kagawa, 761-1701, Japan
Ikeda Hospital | Kanoya, Kagoshima, 893-0024, Japan
Fujisawa City Hospital | Fujisawa, Kanagawa, 251-8550, Japan
Koukan Clinic | Kawasaki, Kanagawa, 210-0852, Japan
Showa University Fujigaoka Hospital | Yokohama, Kanagawa, 227-8501, Japan
Yokosuka Kyosai Hospital | Yokosuka, Kanagawa, 238-8558, Japan
Arao Municipal Hospital | Arao, Kumamoto, 864-0041, Japan
JCHO Yokkaichi Hazu Medical Center | Yokkaichi, Mie, 510-0016, Japan
Japanese Red Cross Ishinomaki Hospital | Ishinomaki, Miyagi, 986-8522, Japan
Asama Nanroku Komoro Medical Center | Komoro, Nagano, 384-8588, Japan
Niigata Prefectural Shibata Hospital | Shibata, Niigata, 957-8588, Japan
R.I.A.C Naha City Hospital | Naha, Okinawa, 902-8511, Japan
Osaka Pref. Saiseikai Tondabayashi Hospital | Tondabayashi, Osaka, 584-0082, Japan
Kitasato University Medical Center | Kitamoto, Saitama, 364-8501, Japan
Iwata City Hospital | Iwata, Shizuoka, 438-8550, Japan
Toshima Hospital | Itabashi-ku, Tokyo, 173-0015, Japan
Nihon University Itabashi Hospital | Itabashi-ku, Tokyo, 173-8610, Japan
Showa University Koto Toyosu Hospital | Koto-ku, Tokyo, 135-8577, Japan
National Hospital Organization Tokyo Medical Center | Meguro-ku, Tokyo, 152-8902, Japan
University of Yamanashi Hospital | Chuo, Yamanashi, 409-3898, Japan
Fukui Prefectural Hospital | Fukui, 910-8526, Japan
National Hospital Organization Kyushu Medical Center | Fukuoka, 810-8563, Japan
Kyushu University Hospital | Fukuoka, 812-8582, Japan
Fukuoka University Hospital | Fukuoka, 814-0180, Japan
Asahi University Hospital | Gifu, 500-8523, Japan
National Hospital Organization Kochi National Hospital | Kochi, 780-8077, Japan
Miyazaki Prefectural Miyazaki Hospital | Miyazaki, 880-8510, Japan
Nara Prefecture General Medical Center | Nara, 630-8581, Japan
Japanese Red Cross Oita Hospital | Oita, 870-0033, Japan
Kitano Hospital | Osaka, 530-8480, Japan
Yodogawa Christian Hospital | Osaka, 533-0024, Japan
National Hospital Organization Osaka National Hospital | Osaka, 540-0006, Japan
Osaka Red Cross Hospital | Osaka, 543-8555, Japan
Nippon Life Hospital | Osaka, 550-0006, Japan
Chibune Clinic | Osaka, 555-0001, Japan
Osaka General Medical Center | Osaka, 558-8558, Japan
Social Corporation Keigakukai Minamiosaka Hospital | Osaka, 559-0012, Japan
Shizuoka Saiseikai General Hospital | Shizuoka, 422-8527, Japan
Suruga Clinic | Shizuoka, 424-0855, Japan
Wakayama Medical University Hospital | Wakayama, 641-8510, Japan
Location Countries

Japan

Verification Date

February 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Molidustat (BAY85-3934)

Type: Experimental

Description: Molidustat group

Label: Darbepoetin alfa

Type: Active Comparator

Description: Darbepoetin alfa group

Acronym MIYABI ND-M
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov