Anemia, Renal Insufficiency, Chronic
Conditions
Keywords
Renal anemia
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)
Interventions
Starting dose of 25 mg or 50 mg molidustat once daily (OD) will be titrated based on the subject's Hb response
DRUGDarbepoetin alfa
Starting dose and frequency of darbepoetin alfa are based on previous ESA. The dose will be titrated based on the subject's Hb response
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Responder rate: proportion of responders among the subjects | From 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 |
| 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 | Defined as change in Hb level / duration between two visits (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 | — |
| Proportion of subjects whose hemoglobin levels are above the target range | Up to 52 weeks | — |
| Proportion of subjects who meet each component of the response | From 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 |
Countries
Japan
Outcome results
None listed