A Safety and Tolerability Study of Zerenex (Ferric Citrate) in Patients With End-Stage Renal Disease (ESRD)

• Sponsor: Keryx Biopharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00648167
• Collaborator: Collaborative Study Group (CSG) (Other)
• Enrollment: 55
• Location: 1
• Arm: 1
• Duration (Months): 10.1
• Patients Per Site Per Month: 5.5

Study Details

Study Description

Brief Summary

This study is to evaluates the safety and tolerability of Zerenex™ (ferric citrate) as a treatment for hyperphosphatemia in patients with End-Stage Renal Disease.

Condition or Disease	Intervention/Treatment	Phase
Hyperphosphatemia; End-stage Renal Disease	Drug: ferric citrate	Phase 2

Detailed Description

The purpose of this study is to evaluate the safety and tolerability of Zerenex™ (ferric citrate) as a treatment for hyperphosphatemia in patients with End-Stage Renal Disease. These patients will be switched to Zerenex™ from their current high dose of phosphate binder and, based on their serum phosphorus levels, will be titrated up from 3.4g/day of Zerenex™ to maximum tolerated and safe doses of Zerenex™. Doses will be adjusted weekly, based on serum phosphorus levels, with the maximum dose administered being approximately 12g/day.

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Safety and Tolerability Study of Zerenex (Ferric Citrate) in Patients With End-Stage Renal Disease (ESRD)
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KRX-0502 (ferric citrate) All patients will be switched from their current phosphate binder to Zerenex, and titrated to the maximum tolerated dose (up to about 12g/day) based on their serum phosphorus levels.	Drug: ferric citrate; ferric citrate will be provided as a 375mg capsule. Dosing and frequency are dependent on patient's serum phosphorus levels. Dosing will occur over the 28-day study.; Other Names: KRX-0502

Outcome Measures

Primary Outcome Measures

1. The Difference in Serum Phosphorus Between Baseline (Day 0) and End of Treatment (Day 28) [28 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and non-pregnant, nonlactating females

• Age > 18 years

• On thrice weekly hemodialysis for at least the previous 3 months prior to randomization

• Phosphorous levels ≥3.5mg/dL at Screening Visit

• On at least 12 tablets/capsules/day of calcium acetate (667mg), calcium carbonate (500mg), lanthanum carbonate (500mg), sevelamer hydrochloride (800mg or two 400mg tablets), or any combination of these agents

• Serum ferritin <1000micrograms/L and Transferrin Saturation (TSAT) <50%

• Willing to be discontinued from current phosphate binder(s) and initiated on Zerenex

• Willing and able to give informed consent

Exclusion Criteria:

• Parathyroidectomy within 6 months prior to Screening

• Actively symptomatic GI disease such as peptic ulcer disease, gastro esophageal reflux, diverticulosis, irritable bowel syndrome (treated asymptomatic is permitted)

• History of documented inflammatory bowel disease or erosive esophagitis

• Serum Phosphorus levels >10.0 mg/dL documented in the 3 monthly laboratories (done routinely in the dialysis unit) in the 3 months prior to the Screening Visit

• History of multiple drug allergies

• History of malignancy in the last 5 years (treated cervical or skin cancer may be permitted if approved by CCC)

• Previous intolerance to oral ferric citrate

• Absolute requirement for oral iron therapy

• Absolute requirement for Vitamin C (multivitamins [Neprocaps, Renaphro, etc.] allowed)

• Absolute requirement for calcium, magnesium, or aluminum containing drugs with meals

• Psychiatric disorder that interferes with the patient's ability to comply with the study protocol

• Inability to tolerate oral drug intake

• Planned surgery or hospitalization during the study (scheduled outpatient access surgery allowed)

• Any other medical condition that renders the patient unable to or unlikely to complete the study or that would interfere with optimal participation in the study or produce significant risk to the patient

• Receipt of any investigational drug within 30 days of randomization

• Inability to cooperate with study personnel or history of noncompliance

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Keryx Biopharmaceuticals
• Collaborative Study Group (CSG)

Investigators

• Study Chair: Julia B Lewis, MD, Collaborative Study Group at the Nephrology Clinical Trials Center, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Sponsor

Publications

None provided.

• Responsible Party: Keryx Biopharmaceuticals
• ClinicalTrials.gov Identifier: NCT00648167
• Other Study ID Numbers: KRX-0502-201
• First Posted: Apr 1, 2008
• Last Update Posted: Apr 4, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Keryx Biopharmaceuticals: ESRD; end-stage renal disease; end stage renal disease; hemodialysis; dialysis; kidney failure; renal failure; kidney; renal; phosphate binder; phosphorus
• Additional relevant MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Hyperphosphatemia

Study Results

Participant Flow

Arm/Group Title	KRX-0502
Arm/Group Description	Ferric Citrate
Period Title: Overall Study
STARTED	55
Start Dose 4.5 g/Day	34
Start Dose 6 g/Day	21
COMPLETED	48
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	KRX-0502
Arm/Group Description	Subjects in this group were initiated on a dose of 4.5 g/day (34 subjects) or 6.0 g/day (21 subjects) of KRX-0502 (ferric citrate)
Overall Participants	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.46 (11.48)
Sex: Female, Male (Count of Participants)
Female	23 41.8%
Male	32 58.2%
Region of Enrollment (participants) [Number]
United States	50 90.9%
Puerto Rico	5 9.1%

Outcome Measures

1. Primary Outcome

Title	The Difference in Serum Phosphorus Between Baseline (Day 0) and End of Treatment (Day 28)
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KRX-0502 (Ferric Citrate)
Arm/Group Description	Patients starting dose of 4.5 grams per day (n=34) and those starting on 6.0 grams per day (n=21)- immediate roll over from previous phosphate binder(s)
Measure Participants	55
Baseline	5.9 (1.4)
Day 28	5.4 (1.4)

Adverse Events

Arm/Group Title	KRX-0502
Arm/Group Description	Subjects in this group were initiated on a dose of 4.5 g/day (34 subjects) or 6.0 g/day (21 subjects) of KRX-0502 (ferric citrate) Intent-to-Treat (ITT)
All Cause Mortality
	KRX-0502
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	KRX-0502
	Affected / at Risk (%)	# Events
Total	4/55 (7.3%)
Cardiac disorders
Worsened congestive heart failure	1/55 (1.8%)	1
Infections and infestations
Liver infection	1/55 (1.8%)	1
Methicillin - susceptible staphylococcus aureus bacteremia	1/55 (1.8%)	1
Psychiatric disorders
Suicide attempt	1/55 (1.8%)	1
Other (Not Including Serious) Adverse Events
	KRX-0502
	Affected / at Risk (%)	# Events
Total	46/55 (83.6%)
Gastrointestinal disorders
Stool color abnormality	34/55 (61.8%)
Diarrhea	14/55 (25.5%)
Constipation	11/55 (20%)
Nausea	5/55 (9.1%)
Vomiting	5/55 (9.1%)
Bloating	4/55 (7.3%)
Heartburn	4/55 (7.3%)
Stomach pain or cramp	4/55 (7.3%)
Increased appetite	3/55 (5.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.