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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00761657
Recruitment Status : Completed
First Posted : September 29, 2008
Results First Posted : November 19, 2021
Last Update Posted : November 19, 2021
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
FibroGen

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Anemia Drug: Roxadustat Drug: Placebo Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 117 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 1, 2006
Actual Primary Completion Date : June 21, 2010
Actual Study Completion Date : June 21, 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Roxadustat
Capsule
Other Name: FG-4592

Experimental: 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.
Drug: Roxadustat
Capsule
Other Name: FG-4592

Experimental: 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.
Drug: Roxadustat
Capsule
Other Name: FG-4592

Experimental: 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.
Drug: Roxadustat
Capsule
Other Name: FG-4592

Experimental: 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.
Drug: Roxadustat
Capsule
Other Name: FG-4592

Experimental: 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.
Drug: Roxadustat
Capsule
Other Name: FG-4592

Experimental: 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.
Drug: Roxadustat
Capsule
Other Name: FG-4592

Experimental: 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.
Drug: Roxadustat
Capsule
Other Name: FG-4592

Placebo Comparator: Placebo
Participants will receive placebo orally, matching to the roxadustat dose, number of days per week, and duration.
Drug: Placebo
Capsule




Primary Outcome Measures :
  1. Primary Safety Outcome Measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Treatment Discontinuation (Parts 1 and 2 Combined) [ Time Frame: Baseline up to Week 16 (End of Study (EoS]) ]
    An adverse event (AE) was any untoward medical event in a participant who received study drug whether or not the event is considered drug related. TEAEs defined as an AE beginning after first dose of study drug until 28 days after last dose of study drug or existing AEs that worsened after first dose of study drug until the participant's last study visit. Severe AEs defined as incapacitating, inability to perform usual activities. Drug-related TEAEs defined as TEAEs with possible, probable, or definite relationship to study drug. Serious AE criteria included death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed here. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  2. Co-Primary Efficacy Outcome Measure: Change From Baseline in Hb at Day 26-29 (End of Treatment) [ Time Frame: Baseline, End of Treatment (EoT) (Day 26 for TIW Dosing or Day 29 for BIW Dosing) ]
    Mean Hb change from baseline was analyzed by treatment group and study visit. Baseline was defined as the mean of last 3 available values prior to the first dose.

  3. Co-Primary Efficacy Outcome Measure: Change From Baseline in Hb at Week 8 (2 Weeks of Follow Up) [ Time Frame: Baseline, Week 8 (2 Weeks of Follow Up) ]
    Mean Hb change from baseline was analyzed by treatment group and study visit. Baseline is defined as the mean of last 3 available values prior to the first dose.


Secondary Outcome Measures :
  1. Number of Participants With a Hemoglobin Response (Not Due to a RBC Transfusion or IV Iron Supplementation During Treatment) [ Time Frame: Baseline up to Day 26-29 (EoT), up to Week 8 (2 weeks of follow up), and up to Week 16 (EoS, 4 weeks of follow up) ]
    Hb response defined as an increase in Hb from baseline by ≥1.0 g/dL (not due to red blood cell transfusion or IV iron supplementation during treatment). The baseline for Hb was defined as the mean of the last 3 available Hb values obtained prior to the first dose.

  2. Plasma Roxadustat Concentration (Part 2) [ Time Frame: Predose on Days 3 (TIW dose groups) or 4 (BIW dose groups), 8, 15, 22, and 26 (TIW dose groups) or 29 (BIW dose groups) ]
  3. Change From Baseline in Plasma Erythropoietin in Part 1 Participants at Day 26 or Day 29 [ Time Frame: Baseline (Day 1), 1, 2, 3, 4, 6, 8, 12, 18, 24, 48, and 72 hours on Day 26 (TIW Dosing) or Day 29 (BIW Dosing) ]
    Baseline is defined as the last value obtained prior to the first dose.

  4. Change From Baseline in Plasma Erythropoietin in Part 2 Participants at 4, 8, 12, and 24 Hours on Day 1 [ Time Frame: Baseline, 4, 8, 12, and 24 hours on Day 1 ]
    Baseline is defined as the last value obtained prior to the first dose.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00761657


Locations
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United States, Arizona
Peoria, Arizona, United States, 85381
Tempe, Arizona, United States, 85284
United States, California
Los Angeles, California, United States, 90095
Mission Viejo, California, United States, 92691
Sacramento, California, United States, 95825
San Diego, California, United States, 92123
Whittier, California, United States, 90603
United States, Colorado
Arvada, Colorado, United States, 80002
Westminster, Colorado, United States, 80031
United States, Connecticut
Middlebury, Connecticut, United States, 06762
United States, Florida
Ocala, Florida, United States, 34471
Panama City, Florida, United States, 32401
Pembroke Pines, Florida, United States, 33028
Tampa, Florida, United States, 33614
United States, Georgia
Augusta, Georgia, United States, 30901
United States, Illinois
Chicago, Illinois, United States, 60616
Evergreen Park, Illinois, United States, 60805
United States, Kansas
Wichita, Kansas, United States, 67214
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Louisiana
Baton Rouge, Louisiana, United States, 70809
Shreveport, Louisiana, United States, 71101
United States, Michigan
Detroit, Michigan, United States, 48236
United States, Nebraska
Lincoln, Nebraska, United States, 68510
United States, Nevada
Las Vegas, Nevada, United States, 89106
United States, New York
Flushing, New York, United States, 11355
United States, North Carolina
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Cleveland, Ohio, United States, 44109
Toledo, Ohio, United States, 43606
United States, Oregon
Medford, Oregon, United States, 97504
United States, Pennsylvania
Wynnewood, Pennsylvania, United States, 19096
United States, South Carolina
Columbia, South Carolina, United States, 29203
Orangeburg, South Carolina, United States, 29118
United States, Tennessee
Chattanooga, Tennessee, United States, 37404
United States, Texas
Houston, Texas, United States, 77036
Sponsors and Collaborators
FibroGen
Astellas Pharma Inc
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: FibroGen
ClinicalTrials.gov Identifier: NCT00761657    
Other Study ID Numbers: FGCL-SM4592-017
First Posted: September 29, 2008    Key Record Dates
Results First Posted: November 19, 2021
Last Update Posted: November 19, 2021
Last Verified: November 2021
Keywords provided by FibroGen:
Kidney
Chronic Kidney Disease
CKD
Stage 3 or 4 Chronic Kidney Disease
Renal
Anemia
Oral anemia treatment
Hemoglobin levels
Blood count
Erythropoietin
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Renal Insufficiency, Chronic
Anemia
Hematologic Diseases
Urologic Diseases
Renal Insufficiency