Clinical trial NCT03418168: A Study of Molidustat for Treatment of Renal Anemia in Peritoneal Dialysis Subjects
Official title: An Open-label, Multicenter Study to Investigate the Efficacy and Safety of Oral Molidustat in Peritoneal Dialysis Subjects With Renal Anemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
Renal Insufficiency, Chronic
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-02-01
Enrollment: 51
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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)

Primary outcomes:
measure: Responder rate: proportion of responders among the subjects
timeFrame: Week 30 to 36
Secondary outcomes:
measure: Mean Hb (Hemoglobin) level
timeFrame: Week 30 to 36
measure: Change in mean Hb level
timeFrame: Baseline and Week 30 to 36
measure: Rate of rise in Hb (Hemoglobin) level (g/dL/week)
timeFrame: Up to 8 weeks
measure: Rate of rise in Hb (Hemoglobin) level (g/dL/week)
timeFrame: Up to 4 weeks
measure: Proportion of subjects who meet each component of the response
timeFrame: Week 30 to 36
measure: Hb level
timeFrame: Baseline and Up to Week 36
measure: Change in Hb level
timeFrame: Baseline and Up to Week 36
measure: Proportion of subjects with mean hemoglobin levels are in the target range
timeFrame: Week 30 to 36
measure: Proportion of subjects with mean hemoglobin levels are above the target range
timeFrame: Week 30 to 36
measure: Proportion of subjects with mean hemoglobin levels are below the target range
timeFrame: Week 30 to 36
measure: Proportion of subjects with hemoglobin levels in the target range
timeFrame: Up to 36 weeks
measure: Proportion of subjects with hemoglobin levels above the target range
timeFrame: Up to 36 weeks
measure: Proportion of subjects with hemoglobin levels below the target range
timeFrame: Up to 36 weeks
measure: Proportion of subjects whose maximum rise in Hb between each consecutive visits is above 0.5 g/dL/week
timeFrame: Up to 36 weeks
measure: Percentage of days in the target Hb range during the evaluation period
timeFrame: Week 30 to 36
measure: Percentage of days in the target Hb range during the treatment period
timeFrame: Up to 36 weeks
measure: Rate of rise in Hb level (g/dL/week) between each consecutive visits
timeFrame: Up to 36 weeks
measure: Percentage of Hb levels in target range during the evaluation period
timeFrame: Week 30 to 36
measure: Percentage of Hb levels in target range during the treatment period
timeFrame: Up to 36 weeks
measure: Proportion of subjects who received at least one rescue treatment
timeFrame: Up to 36 weeks
measure: Proportion of subjects whose Hb level was ≥ 13.0 g/dL or < 8.0 g/dL
timeFrame: Up to 36 weeks
measure: Number of participants with serious adverse events
timeFrame: Up to 36 weeks
measure: Maximum concentration (Cmax) of Molidustat
timeFrame: Baseline, Week 8, Wee16 and Week 36
measure: Area under the concentration-time curve (AUC) of Molidustat
timeFrame: Baseline, Week 8, Wee16 and Week 36
measure: EPO (Erythropoietin) serum concentration of Molidustat
timeFrame: Baseline, Week 8, Wee16 and Week 36
Other outcomes:
Locations:
city: Yatomi
country: Japan
facility: Kainan Hospital
state: Aichi
city: Matsuyama
country: Japan
facility: Ehime Prefectural Central Hospital
state: Ehime
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Kitakyushu
country: Japan
facility: JCHO Kyushu Hospital
state: Fukuoka
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Sapporo
country: Japan
facility: Elm Grove Clinic
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Fujisawa
country: Japan
facility: Fujisawa City Hospital
state: Kanagawa
city: Kamakura
country: Japan
facility: Shonan Kamakura General Hospital
state: Kanagawa
city: Kawasaki
country: Japan
facility: Toranomon Hospital Kajigaya
state: Kanagawa
city: Yokohama
country: Japan
facility: Showa University Fujigaoka Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku Medical and Pharmaceutical University Hospital
state: Miyagi
city: Shibata
country: Japan
facility: Niigata Prefectural Shibata Hospital
state: Niigata
city: Beppu
country: Japan
facility: National Hospital Organization Beppu Medical Center
state: Oita
city: Uruma
country: Japan
facility: Okinawa prefectural Chubu Hospital
state: Okinawa
city: Izumi
country: Japan
facility: Fuchu Hospital
state: Osaka
city: Fukui
country: Japan
facility: Fukui-ken Saiseikai Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Fukuoka
country: Japan
facility: Japanese Red Cross Fukuoka Hospital
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Gifu
country: Japan
facility: Asahi University Hospital
city: Kyoto
country: Japan
facility: National Hospital Organization Kyoto Medical Center
city: Nara
country: Japan
facility: Nara Prefecture General Medical Center
city: Niigata
country: Japan
facility: Niigata City General Hospital
city: Oita
country: Japan
facility: Japanese Red Cross Oita Hospital
city: Osaka
country: Japan
facility: Osaka General Medical Center
Study officials:
References:
citation: 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.