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

A Randomized, Single-blind, Placebo-controlled, 4-Week Treatment Study of the Safety and Biologic Activity of Escalating Multiple Oral Doses of FG-4592 in Subjects With Chronic Kidney Disease Not Requiring Dialysis

The primary objective of the study is to evaluate the safety, tolerability, and pharmacodynamic effects of different oral doses of roxadustat administered 2 times a week (BIW) or 3 times a week (TIW) for up to 4 weeks to participants with chronic kidney disease (CKD) 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:

1. 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.
2. Chronic Kidney Disease Stage 3 or 4 with hemoglobin <11.0 grams (g)/deciliter (dL).
3. Normal iron studies.
4. Normal folate and vitamin B12 levels.
5. Liver function tests within normal limits at screening.
6. Absence of active or chronic rectal bleeding.
7. 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.
8. Female participants must not be pregnant nor breastfeeding and agree to use acceptable method of contraception.
9. Male participants with partners who can have children must agree to use a medically acceptable method of contraception.

Exclusion Criteria:

1. Seropositive for HIV.
2. History of chronic liver disease.
3. History of polycystic kidney disease (PKD).
4. Uncontrolled hypertension (diastolic BP >110 millimeter of mercury (mmHg) or systolic BP >170 mmHg at screening).
5. New York Heart Association Class III or IV congestive heart failure.
6. Recent myocardial infarction or acute coronary syndrome.
7. History of myelodysplastic syndrome.
8. 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.
9. Active inflammatory infection or chronic inflammatory disease.
10. Any clinically significant and uncontrolled medical condition considered a high risk for participation in an investigational study.
11. Blood clots within 4 weeks.
12. History of ongoing hemolysis or diagnosis of hemolytic syndrome.
13. Known history of bone marrow fibrosis.
14. History of hemosiderosis or hemochromatosis.
15. Androgen therapy within 12 weeks.
16. Red blood cell transfusion within 12 weeks.
17. Therapy with an erythropoiesis stimulating agent (ESA) such as human recombinant erythropoietin within the past 60 days.
18. Intravenous iron supplementation within the past 60 days.
19. Currently taking dapsone or acetaminophen >2.6 g/day.
20. History of prior organ transplantation.
21. Alcohol consumption greater than 3 or more drinks per day within the past year.
22. Use of an investigational medication or participation in an investigational study within 4 weeks preceding Day 1.
23. Positive urine toxicology screen for a substance that has not been prescribed for the participant.