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

NCT ID: NCT00761657

Last Updated: 2021-11-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

117 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-01

Study Completion Date

2010-06-21

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Chronic Kidney Disease Anemia

Keywords

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Kidney Chronic Kidney Disease CKD Stage 3 or 4 Chronic Kidney Disease Renal Anemia Oral anemia treatment Hemoglobin levels Blood count Erythropoietin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Roxadustat 0.7 mg/kg BIW

Participants will receive roxadustat 0.7 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

Capsule

Roxadustat 0.7 mg/kg TIW

Participants will receive roxadustat 0.7 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

Capsule

Roxadustat 1.0 mg/kg BIW

Participants will receive roxadustat 1.0 mg/kg BIW orally with doses administered at least 72 hours apart for 29 days.

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

Capsule

Roxadustat 1.0 mg/kg TIW

Participants will receive roxadustat 1.0 mg/kg TIW orally with doses administered at least 48 hours apart for 26 days.

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

Capsule

Roxadustat 1.5 mg/kg BIW

Participants will receive roxadustat 1.5 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

Capsule

Roxadustat 1.5 mg/kg TIW

Participants will receive roxadustat 1.5 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

Capsule

Roxadustat 2.0 mg/kg BIW

Participants will receive roxadustat 2.0 mg/kg BIW orally with doses administered at least 68 hours apart for 29 days.

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

Capsule

Roxadustat 2.0 mg/kg TIW

Participants will receive roxadustat 2.0 mg/kg TIW orally with doses administered at least 46 hours apart for 26 days.

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

Capsule

Placebo

Participants will receive placebo orally, matching to the roxadustat dose, number of days per week, and duration.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Capsule

Interventions

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Roxadustat

Capsule

Intervention Type DRUG

Placebo

Capsule

Intervention Type DRUG

Other Intervention Names

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FG-4592

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Astellas Pharma Inc

INDUSTRY

Sponsor Role collaborator

FibroGen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Peoria, Arizona, United States

Site Status

Tempe, Arizona, United States

Site Status

Los Angeles, California, United States

Site Status

Mission Viejo, California, United States

Site Status

Sacramento, California, United States

Site Status

San Diego, California, United States

Site Status

Whittier, California, United States

Site Status

Arvada, Colorado, United States

Site Status

Westminster, Colorado, United States

Site Status

Middlebury, Connecticut, United States

Site Status

Ocala, Florida, United States

Site Status

Panama City, Florida, United States

Site Status

Pembroke Pines, Florida, United States

Site Status

Tampa, Florida, United States

Site Status

Augusta, Georgia, United States

Site Status

Chicago, Illinois, United States

Site Status

Evergreen Park, Illinois, United States

Site Status

Wichita, Kansas, United States

Site Status

Louisville, Kentucky, United States

Site Status

Baton Rouge, Louisiana, United States

Site Status

Shreveport, Louisiana, United States

Site Status

Detroit, Michigan, United States

Site Status

Lincoln, Nebraska, United States

Site Status

Las Vegas, Nevada, United States

Site Status

Flushing, New York, United States

Site Status

Winston-Salem, North Carolina, United States

Site Status

Cleveland, Ohio, United States

Site Status

Toledo, Ohio, United States

Site Status

Medford, Oregon, United States

Site Status

Wynnewood, Pennsylvania, United States

Site Status

Columbia, South Carolina, United States

Site Status

Orangeburg, South Carolina, United States

Site Status

Chattanooga, Tennessee, United States

Site Status

Houston, Texas, United States

Site Status

Countries

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United States

References

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Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

Reference Type DERIVED
PMID: 36005278 (View on PubMed)

Besarab A, Provenzano R, Hertel J, Zabaneh R, Klaus SJ, Lee T, Leong R, Hemmerich S, Yu KH, Neff TB. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients. Nephrol Dial Transplant. 2015 Oct;30(10):1665-73. doi: 10.1093/ndt/gfv302. Epub 2015 Aug 3.

Reference Type DERIVED
PMID: 26238121 (View on PubMed)

Other Identifiers

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FGCL-SM4592-017

Identifier Type: -

Identifier Source: org_study_id