Ferric Citrate for the Treatment of Hyperphosphatemia in Patients With Chronic Kidney Disease Undergoing Hemodialysis

A Multicenter, Randomized, Open-Label, Active-Controlled, Parallel Study to Assess the Efficacy and Safety of Ferric Citrate Capsules for the Treatment of Hyperphosphatemia in Patients With Chronic Kidney Disease Undergoing Hemodialysis

To evaluate the efficacy and safety of ferric citrate capsules for the treatment of hyperphosphatemia in patients with chronic kidney disease undergoing hemodialysis

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease; ESRD; Hyperphosphatemia
• Intervention / Treatment: Drug: Ferric Citrate; Drug: Sevelamer Carbonate

Detailed Description

This is a multicenter, randomized, open-label, active-controlled, parallel, phase III study which aims to assess the efficacy and safety of ferric citrate capsules for the treatment of hyperphosphatemia in patients with chronic kidney disease undergoing hemodialysis. This study is consisting of a Screening/Washout period (14 days) and a Treatment/Observation period (12 weeks). During the Treatment period, the subjects will be randomly assigned to the ferric citrate capsule group (study group) or sevelamer carbonate tablet group (control group) in the ratio of 1:1.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Baotou, China
    • Baotou Central Hospital
  • Beijing, China
    • The General Hospital of the People's Liberation Army (PLAGH)
  • Changchun, China
    • the Second Hospital of Jilin University
  • Chongqing, China
    • Daping Hospital
  • Dalian, China
    • The First Affiliated Hospital of Dalian Medical University
  • Guangzhou, China
    • The Fifth Affiliated Hospital of Guangzhou Medical University
  • Guangzhou, China
    • The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University
  • Jilin, China
    • Jilin Guowen Hospital
  • Jiujiang, China
    • Jiujiang University Affiliated Hospital
  • Meihekou, China
    • Meihekou Central Hospital
  • Nanchang, China
    • The First Affiliated Hospital of Nanchang University
  • Nanchang, China
    • Jiangxi Provincial People's Hospital
  • Nanjing, China
    • BenQ Medical Center
  • Nanjing, China
    • Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University)
  • Nanjing, China
    • The Second Affiliated Hospital of Nanjing Medical University
  • Qingdao, China
    • The Affiliated Hospital of Qingdao University
  • Shanghai, China
    • Changhai Hospital
  • Shenyang, China
    • Shengjing Hospital of China Medical University
  • Tonghua, China
    • Tonghua Central Hospital
  • Wuhan, China
    • Renmin Hospital of Wuhan University
  • Wuhan, China
    • Zhongnan Hospital of Wuhan University
  • Wuhan, China
    • Fifth Hospital in Wuhan
  • Zhengzhou, China
    • Henan Provincial People's Hospital
  • Zunyi, China
    • Affiliated Hospital of Zunyi Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Willing to give written informed consent.;
2. Between the age of 18 and 75 years (including the boundary value);
3. Patients who maintain the hemodialysis schedule as 3 times a week and the dialysis schedule should remain unchanged during the study period;
4. At Screening, patients who have received phosphate binder for at least 4 weeks and have a serum phosphorus level between 2.5 and 8.0 mg/dL (0.81 to 2.58 mmol/L) (excluding the boundary value) after treatment;
5. Patients with a serum phosphorus level between 5.5 and 10.0 mg/dL (1.78 to 3.23 mmol/L) (excluding the boundary value) after washout.

Exclusion Criteria:

1. Patients with severe gastrointestinal diseases (such as acute peptic ulcer, chronic ulcerative colitis, regional enteritis, ileus) or patients with dysphagia;
2. Patients with a history of gastrectomy or enterectomy (excluding endoscopic excision or caecectomy) or patients who had undergone gastrointestinal surgery within 3 months prior to Screening;
3. Patients with severe constipation (times of bowel movement≤ 1 time/week), chronic diarrhea (times of bowel movement≥ 4 times/day), severe gastrointestinal motility disorder;
4. Patients with hemochromatosis or patients receiving treatment for iron overload, or patients with a serum ferritin level >800 ng/mL or TSAT >50% at Screening;
5. Patients with a serum calcium level (corrected) <8.0 mg/dL (2.0 mmol/L) or >11.0 mg/dL (2.75 mmol/L) after washout;
6. Patients with intact-PTH>800pg/mL at Screening, or patients undergone parathyroid surgery within 6 months prior to Screening or requiring parathyroid surgery;
7. Patients who received blood transfusions for treating anemia within 3 months prior to Screening;
8. Patients who require phosphorus-binding agents containing aluminum, magnesium, calcium and lanthanum in addition to the study drug or patients who require an antacid with a phosphorus binding effect during the study period;
9. Patients who require citrate preparation as an anticoagulant during hemodialysis treatment during the study period;
10. Patients with impaired liver function (hepatic dysfunction or serum total bilirubin, aspartate aminotransferase or alanine aminotransferase ≥ 2 times the upper limit of normal) or patients with cirrhosis;
11. Patients with cerebrovascular disease (cerebral infarction, cerebral hemorrhage, etc.) or cardiovascular disease (congestive heart failure of Class III or severer in NYHA classification, acute myocardial infarction, unstable angina, etc.) requiring hospitalization within 6 months prior to Screening;
12. Patients who are known to be intolerant to sevelamer carbonate tablet;
13. Patients with a history of allergies to iron preparations or those who are intolerant to iron preparations;
14. Patients who are scheduled to have a kidney transplant during the study period;
15. Patients with a current or past history of malignancy within 5 years prior to Screening;
16. Women who are pregnant or lactating, or patients who are unable to take effective contraception from screening to 6 months after discontinuation (including male subjects and their female spouses);
17. Patients who had participated in other clinical studies and other received investigational drug product within 1 month or 5 half-lives of the drug product (whichever is longer) prior to Screening;
18. Patients who are not suitable for participating in the trial according to the investigator's judgment;
19. Patients who are unwilling or unable to follow the protocol process.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ferric Citrate Capsule; Ferric Citrate Capsule, product specification: 500 mg/cap, manufactured by Panion & BF Biotech Inc.	Drug: Ferric Citrate; Take the capsules with meals or immediately after meals.
ACTIVE_COMPARATOR: Sevelamer Carbonate Tablet; Sevelamer carbonate tablet group, product specification: 800 mg/tablet, manufactured by Genzyme Ireland Limited	Drug: Sevelamer Carbonate; Take the tablets with meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in serum phosphorus levels	The change in serum phosphorus levels at the end of treatment (Visit 10 or ET) as compared to baseline (before the first dose).	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum phosphorus levels	Serum phosphorus levels at the end of treatment;	12 Weeks
The proportion of subjects whose serum phosphorus levels reached the target range.	The proportion of subjects whose serum phosphorus levels reached the target range (3.5 to 5.5 mg/dL, 1.13 to 1.78 mmol/L) at the end of the treatment;	12 Weeks
The response rate of serum phosphorus	The response rate of serum phosphorus at the end of treatment (defined as reduction of the serum phosphorus level exceeds 25% as compared to baseline);	12 Weeks
The change in serum calcium (corrected) levels	The change in serum calcium (corrected) levels at the end of treatment as compared to baseline;	12 Weeks
The change in the [Ca] × [P] product relative	The change in the [Ca] × [P] product relative at the end of treatment as compared to baseline;	12 Weeks
The change in the level of intact-PTH levels	The change in the level of intact-PTH levels at the end of treatment as compared to baseline.	12 Weeks

Collaborators and Investigators

• Sponsor: Panion & BF Biotech Inc.
• Collaborators: Shandong Weigao Panion Pharmaceutical Co. Ltd.
• Investigators: Principal Investigator: Xiangmei Chen, The General Hospital of the People's Liberation Army (PLAGH)

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 19, 2019
• Primary Completion (ACTUAL): February 20, 2021
• Study Completion (ACTUAL): February 20, 2021

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (ACTUAL): June 13, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 10, 2021
• Last Update Submitted That Met QC Criteria: March 8, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Kidney Failure, Chronic; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Hyperphosphatemia; Phosphorus Metabolism Disorder
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Phosphorus Metabolism Disorders; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Hyperphosphatemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Sevelamer
• Other Study ID Numbers: WG-PBB00302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No