Anemia, Renal Insufficiency, Chronic
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of molidustat in peritoneal dialysis subjects with renal anemia
Interventions
Starting dose of molidustat once daily (OD) will be titrated based on the subject's Hb (Hemoglobin) response
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder rate: proportion of responders among the subjects | Week 30 to 36 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in mean Hb level | Baseline and Week 30 to 36 | — |
| Rate of rise in Hb (Hemoglobin) level (g/dL/week) | Up to 8 weeks | — |
| Proportion of subjects who meet each component of the response | Week 30 to 36 | 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 |
| 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 | — |
| Mean Hb (Hemoglobin) level | Week 30 to 36 | — |
| 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 | Week 30 to 36 | Defined as the number of measurements in the target range / number of measurements x 100 \[%\]) |
| Percentage of Hb levels in target range during the treatment period | Up to 36 weeks | Defined as the number of measurements in the target range / number of measurements x 100 \[%\]) |
| 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 | — |
| Proportion of subjects whose maximum rise in Hb between each consecutive visits is above 0.5 g/dL/week | Up to 36 weeks | Defined as change in Hb level / duration between two visits (weeks) |
Countries
Japan
Outcome results
None listed