Head to Head Study Against Sevelamer Hydrochloride

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00441545
• Collaborator: (none)
• Enrollment: 182
• Locations: 44
• Arms: 2
• Actual Duration (Months): 18.8
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To compare the efficacy of Fosrenol (Lanthanum carbonate) and sevelamer hydrochloride in the reduction of serum phosphorus levels from baseline.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease, Stage 5	Drug: Fosrenol (Lanthanum Carbonate); Drug: Sevelamer hydrochloride	Phase 3

Detailed Description

To compare the efficacy of Fosrenol (Lanthanum carbonate) and sevelamer hydrochloride in the reduction of serum phosphorus levels from baseline.

Study Design

• Study Type: Interventional
• Actual Enrollment: 182 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multicenter, Open-label, Randomized, Cross-over Study to Compare the Efficacy and Safety of Fosrenol® and Sevelamer Hydrochloride in Patients Receiving Hemodialysis for End Stage Renal Disease
• Actual Study Start Date: Jan 5, 2007
• Actual Primary Completion Date: Jul 31, 2008
• Actual Study Completion Date: Jul 31, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Fosrenol (Lanthanum carbonate)	Drug: Fosrenol (Lanthanum Carbonate); The starting dose is a total daily dose of 2250mg of Fosrenol (Lanthanum carbonate) to a maximum dose of 3000mg daily. Chewable tablets will be administered orally with meals in 750mg and 1000mg strength tablets.; Other Names: FOSRENOL
Active Comparator: 2 Sevelamer hydrochloride	Drug: Sevelamer hydrochloride; The starting dose is a total daily dose of 4800mg of sevelamer hydrochloride up to a maximum of 6400 mg daily. Sevelamer hydrochloride 800mg tablets, administered orally with meals.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Serum Phosphorus Levels at 4 Weeks [4 weeks]

Secondary Outcome Measures

1. Change From Baseline in Serum Calcium Levels at 4 Weeks [4 weeks]

2. Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks [Baseline and 4 weeks]

3. Patients Achieving Kidney Disease Outcomes Quality Initiative (KDOQI) Target for Serum Phosphorous at 4 Weeks [4 weeks]

   Kidney Disease Outcomes Quality Initiative (KDOQI) target for serum phosphorous is 3.5 - 5.5 mg/dL (1.13 - 1.77 mmol/L)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults with end stage renal disease who are receiving dialysis

Exclusion Criteria:

• Subjects with significant gastrointestinal disorders

• Subjects who are pregnant or nursing

• Subjects currently taking lanthanum carbonate, sevelamer hydrochloride, cinacalcet hydrochloride

• Subjects who are HIV positive

• Subjects with clinical significant liver disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	DSI Renal Inc.	Mesa	Arizona	United States	85202
2	AKDHC Medical Research Services, LLC	Phoenix	Arizona	United States	85012
3	Southwest Kidney Institute, PLC	Tempe	Arizona	United States	85284
4		Tempe	Arizona	United States	85284
5	University of Arizona Health Service Center	Tucson	Arizona	United States	85724
6	Clinical Research Connections	Jonesboro	Arkansas	United States	72401
7	South Valley Dialysis Center	Encino	California	United States	91316
8	VA Greater Los Angeles Health Care System, West LA	Los Angeles	California	United States	90073
9	Apex Research of Riverside	Riverside	California	United States	92505
10	North Valley Nephrology	Yuba City	California	United States	95991
11	Western Nephrology & Metabolic Bone Disease, PC	Thornton	Colorado	United States	80260
12	Shands University of Florida Outpatient Dialysis	Gainesville	Florida	United States	32608
13	Discovery Medical Research Group	Ocala	Florida	United States	34471
14	Pines Clinical Research	Pembroke Pines	Florida	United States	33028
15	Clinical Research Center of Indian River Medical Center	Vero Beach	Florida	United States
16	Kidney Care Associates, LLC	Augusta	Georgia	United States	30901
17	Renal Physicians of Georgia	Macon	Georgia	United States	31217
18	Evanston Northwestern Hospital	Evanston	Illinois	United States	60201
19	Research by Design, LLC	Evergreen Park	Illinois	United States	60805
20	Nephrology Inc.	Mishawaka	Indiana	United States	46545
21	Renal Associates of Baton Rouge	Baton Rouge	Louisiana	United States	70809
22	Creighton University Medical Center	Omaha	Nebraska	United States	68131
23	Hypertension and Nephrology, Associates	Eatontown	New Jersey	United States	07724
24	Winthrop Dialysis Center	Mineola	New York	United States	11501
25	SUNY at Stony Brook NY	Stony Brook	New York	United States	11794
26	Wake Nephrology Associates	Raleigh	North Carolina	United States	27609
27	Southeastern Nephrology Associates	Wilmington	North Carolina	United States	28401
28	Northwest Renal Clinic	Portland	Oregon	United States	97210
29	Carolina Nephrology, PA	Greenville	South Carolina	United States	29605
30	VA Tennessee Valley Healthcare System	Nashville	Tennessee	United States	37212
31	Rosa Verde Tower	San Antonio	Texas	United States	78205
32	University of Texas Health Science Center at San Antonio Medicine/Nephrology	San Antonio	Texas	United States	78229
33	Alexandria Kidney	Alexandria	Virginia	United States	22304
34	Clinical Research & Consulting Center, LLC	Fairfax	Virginia	United States	22030
35	KfH Nierenzentrum/Bad/Konig	Bad Konig		Germany	64732
36	KfH Nierenzentrum	Berlin		Germany	10559
37	KfH Dialysezentrum/Berlin	Berlin		Germany	12045
38	KfH Nierenzentrum/Dulmen	Dulmen		Germany	48249
39	Georg-August-Universitat Universitatsmedizin Abt. Nephrologie u. Rheumatologie	Gottingen		Germany	37075
40	Dialysezentrum Barmbeck	Hamburg		Germany	22297
41	KfH-Nierenzentrum/Jena	Jena		Germany	07751
42	KfH-Dialysezentrum/Rosenheim	Rosenheim		Germany	83022
43	Jose Cangiano, MD	San Juan		Puerto Rico	00918
44	Churchill Hospital Oxford Kidney Unit	Oxford		United Kingdom	OX3 7LJ

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA recall information

Publications

• Sprague SM, Ross EA, Nath SD, Zhang P, Pratt RD, Krause R. Lanthanum carbonate vs. sevelamer hydrochloride for the reduction of serum phosphorus in hemodialysis patients: a crossover study. Clin Nephrol. 2009 Oct;72(4):252-8.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00441545
• Other Study ID Numbers: SPD405-319; 2006-004959-38
• First Posted: Mar 1, 2007
• Last Update Posted: Jun 11, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Sevelamer

Study Results

Participant Flow

Recruitment Details	Following Washout 1, eligible subjects with serum phosphorus levels greater than or equal to 6.0mg/dL (greater than or equal to 1.94mmol/L) and calcium levels greater than or equal to 8.4mg/dL (greater than or equal to 2.10mmol/L) were randomized in a 1:1 ratio to receive either Fosrenol or sevelamer hydrochloride (HCl) for 4 weeks.
Pre-assignment Detail	The study consisted of the following phases: screening (1 week), washout 1 (2 weeks), treatment (4 weeks), Washout 2 (2 weeks), crossover treatment (4 weeks), and a 30-day follow-up

Arm/Group Title	Fosrenol First	Sevelamer HCl First
Arm/Group Description	Fosrenol (Lanthanum carbonate) dosing began at 2250mg/day, administered orally as one 750mg tablet taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 3000mg/day, administered orally as one 1000mg tablet three times per day with meals. Subjects were to remain on the final Fosrenol dose of 3000mg/day for 3 weeks. After washout, patients then crossover to receive Sevelamer HCl for 4 weeks (see below).	Sevelamer HCl dosing began at 4800mg/day, administered orally as two 800mg tablets taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 6400mg/day, administered orally as three 800mg tablets taken two times per day with meals and two 800mg tablets taken once per day with the lighter meal (i.e., a total of eight 800mg tablets per day). Subjects were to remain on the final sevelamer HCl dose of 6400mg/day for 3 weeks. After washout, patients then crossover to receive Fosrenol for 4 weeks (see above).
Period Title: First Intervention
STARTED	95	87
COMPLETED	77	75
NOT COMPLETED	18	12
Period Title: First Intervention
STARTED	77	75
COMPLETED	77	75
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	77	75
COMPLETED	65	68
NOT COMPLETED	12	7

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description
Overall Participants	182
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	140 76.9%
>=65 years	42 23.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.5 (13.10)
Sex: Female, Male (Count of Participants)
Female	80 44%
Male	102 56%
Region of Enrollment (Count of Participants)
United States	139 76.4%
Puerto Rico	1 0.5%
Germany	41 22.5%
United Kingdom	1 0.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Serum Phosphorus Levels at 4 Weeks
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

ITT population defined as subjects who were randomized, received at least one dose of investigational product, and had at least one post-dose assessment of the primary efficacy variable.

Arm/Group Title	Fosrenol	Sevelamer HCl
Arm/Group Description	Lanthanum carbonate
Measure Participants	165	161
Least Squares Mean (Standard Error) [mg/dL]	-1.73 (0.129)	-1.44 (0.132)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fosrenol, Sevelamer HCl
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1130
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Change From Baseline in Serum Calcium Levels at 4 Weeks
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Fosrenol	Sevelamer HCl
Arm/Group Description	Lanthanum carbonate
Measure Participants	165	161
Least Squares Mean (Standard Error) [mg/dL]	0.06 (0.045)	-0.06 (0.046)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fosrenol, Sevelamer HCl
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0249
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Fosrenol	Sevelamer HCl
Arm/Group Description	Lanthanum carbonate
Measure Participants	165	161
Baseline	225.46 (11.094)	225.46 (11.094)
Endpoint	296.48 (17.412)	291.18 (16.181)

4. Secondary Outcome

Title	Patients Achieving Kidney Disease Outcomes Quality Initiative (KDOQI) Target for Serum Phosphorous at 4 Weeks
Description	Kidney Disease Outcomes Quality Initiative (KDOQI) target for serum phosphorous is 3.5 - 5.5 mg/dL (1.13 - 1.77 mmol/L)
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fosrenol	Sevelamer HCl
Arm/Group Description	Lanthanum carbonate
Measure Participants	165	161
Number [Percentage of Participants]	42.7 23.5%	34.6 NaN

Adverse Events

Arm/Group Title	Fosrenol		Sevelamer HCl
Arm/Group Description	Fosrenol (Lanthanum carbonate) dosing began at 2250mg/day, administered orally as one 750mg tablet taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 3000mg/day, administered orally as one 1000mg tablet three times per day with meals. Subjects were to remain on the final Fosrenol dose of 3000mg/day for 3 weeks. After washout, patients then crossover to receive Sevelamer HCl for 4 weeks (see below).		Sevelamer HCl dosing began at 4800mg/day, administered orally as two 800mg tablets taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 6400mg/day, administered orally as three 800mg tablets taken two times per day with meals and two 800mg tablets taken once per day with the lighter meal (i.e., a total of eight 800mg tablets per day). Subjects were to remain on the final sevelamer HCl dose of 6400mg/day for 3 weeks. After washout, patients then crossover to receive Fosrenol for 4 weeks (see above).
All Cause Mortality
	Fosrenol		Sevelamer HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fosrenol		Sevelamer HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/170 (10.6%)		20/163 (12.3%)
Blood and lymphatic system disorders
Anemia	0/170 (0%)		1/163 (0.6%)
Cardiac disorders
Congestive heart failure	1/170 (0.6%)		2/163 (1.2%)
Myocardial infarction	2/170 (1.2%)		2/163 (1.2%)
Coronary atery disease	2/170 (1.2%)		2/163 (1.2%)
Unstable angina	1/170 (0.6%)		0/163 (0%)
Ear and labyrinth disorders
Vertigo	0/170 (0%)		1/163 (0.6%)
Gastrointestinal disorders
Abdominal pain	1/170 (0.6%)		1/163 (0.6%)
General disorders
Weakness	0/170 (0%)		2/163 (1.2%)
Chest pain	2/170 (1.2%)		0/163 (0%)
Infections and infestations
Clostridium difficile colitis	0/170 (0%)		2/163 (1.2%)
Foot infection	1/170 (0.6%)		1/163 (0.6%)
Osteomyelitis	2/170 (1.2%)		1/163 (0.6%)
Cellulitis	1/170 (0.6%)		1/163 (0.6%)
Pneumonia	3/170 (1.8%)		1/163 (0.6%)
Cystitis	1/170 (0.6%)		1/163 (0.6%)
Septic phlebitis	1/170 (0.6%)		0/163 (0%)
Metabolism and nutrition disorders
Hyperkalemia	1/170 (0.6%)		1/163 (0.6%)
Hypoglycemia	0/170 (0%)		1/163 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/170 (0.6%)		0/163 (0%)
Nervous system disorders
Presyncope	0/170 (0%)		1/163 (0.6%)
Stroke	1/170 (0.6%)		0/163 (0%)
Cerebral vascular accident	3/170 (1.8%)		0/163 (0%)
Pripheral neuropathy	1/170 (0.6%)		0/163 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/170 (0%)		1/163 (0.6%)
Dyspnoea	0/170 (0%)		1/163 (0.6%)
Skin and subcutaneous tissue disorders
Extremity necrosis	0/170 (0%)		3/163 (1.8%)
Vascular disorders
Death	1/170 (0.6%)		0/163 (0%)
Hypotension	2/170 (1.2%)		0/163 (0%)
Other (Not Including Serious) Adverse Events
	Fosrenol		Sevelamer HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/170 (18.2%)		27/163 (16.6%)
Gastrointestinal disorders
Nausea	15/170 (8.8%)		9/163 (5.5%)
Diarrhea	12/170 (7.1%)		12/163 (7.4%)
Vomiting	9/170 (5.3%)		6/163 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.