Phase 2 Study of Roxadustat in Participants With Anemia and Chronic Kidney Disease Not Requiring Dialysis

This study in participants with CKD not requiring dialysis was conducted in 2 parts (designated Part 1 and Part 2). Part 1 evaluated roxadustat doses at 1.0 and 2.0 milligrams/kilograms (mg/kg). Part 2 evaluated roxadustat doses at 0.7, 1.5, and 2.0 mg/kg.

On 08 May 2007, the Food and Drug Administration (FDA) placed a clinical hold on the study until evaluation of a report of a death due to fulminant hepatic failure in a participant with CKD in a FibroGen-sponsored clinical trial of another hypoxia inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) (FG-2216) being investigated for treatment of anemia in participants with CKD and other diseases. The clinical hold resulted in early termination of Part 1 of the study. On 24 March 2008, the FDA lifted the clinical hold and Part 2 of this study started.

Inclusion criteria

• 18 to 80 years of age. Participants aged over 75 years but otherwise meet all other participant selection criteria will be evaluated on a case-by-case basis and can be included in this study, per discretion of Sponsor's physician representative such as medical monitor or clinical leader.
• Chronic Kidney Disease Stage 3 or 4 with hemoglobin <11.0 grams (g)/deciliter (dL).
• Normal iron studies.
• Normal folate and vitamin B12 levels.
• Liver function tests within normal limits at screening.
• Absence of active or chronic rectal bleeding.
• Absence of diagnosis of age-related macular degeneration (AMD), diabetic macular edema, or diabetic proliferative retinopathy that is likely to require treatment during the trial.
• Female participants must not be pregnant nor breastfeeding and agree to use acceptable method of contraception.
• Male participants with partners who can have children must agree to use a medically acceptable method of contraception.

Exclusion criteria

• Seropositive for HIV.
• History of chronic liver disease.
• History of polycystic kidney disease (PKD).
• Uncontrolled hypertension (diastolic BP >110 millimeter of mercury (mmHg) or systolic BP >170 mmHg at screening).
• New York Heart Association Class III or IV congestive heart failure.
• Recent myocardial infarction or acute coronary syndrome.
• History of myelodysplastic syndrome.
• Any history of malignancy or a known genetic predisposition for developing cancer (for example, with diagnostic markers suggesting a genetic predisposition of cancer) except for curatively resected basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or resected benign colonic polyps.
• Active inflammatory infection or chronic inflammatory disease.
• Any clinically significant and uncontrolled medical condition considered a high risk for participation in an investigational study.
• Blood clots within 4 weeks.
• History of ongoing hemolysis or diagnosis of hemolytic syndrome.
• Known history of bone marrow fibrosis.
• History of hemosiderosis or hemochromatosis.
• Androgen therapy within 12 weeks.
• Red blood cell transfusion within 12 weeks.
• Therapy with an erythropoiesis stimulating agent (ESA) such as human recombinant erythropoietin within the past 60 days.
• Intravenous iron supplementation within the past 60 days.
• Currently taking dapsone or acetaminophen >2.6 g/day.
• History of prior organ transplantation.
• Alcohol consumption greater than 3 or more drinks per day within the past year.
• Use of an investigational medication or participation in an investigational study within 4 weeks preceding Day 1.
• Positive urine toxicology screen for a substance that has not been prescribed for the participant.