Head to Head Study Against Sevelamer Hydrochloride - Study Results

Study Type:	Interventional
Study Design:	Randomized, Open Label, Active Control, Crossover Assignment
Condition:	Chronic Kidney Disease, Stage 5
Interventions:	Drug: Fosrenol (Lanthanum Carbonate) Drug: Sevelamer hydrochloride

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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 Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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

Reporting Groups

	Description
Fosrenol First	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 First	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).

Description

Fosrenol First

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 First

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).

Participant Flow for 3 periods

Period: First Intervention

	Fosrenol First	Sevelamer HCl First
STARTED	95	87
COMPLETED	77	75
NOT COMPLETED	18	12
Adverse Event	6	5
Protocol Violation	2	2
Withdrawal by Subject	3	3
Kidney transplant	1	1
Lack of Efficacy	2	0
Subject exceeded safety criteria	0	1
Subject met an exclusionary criteria	1	0
Extended hospitalization	1	0
Site error	1	0
Sponsor's request	1	0

Period: Washout

	Fosrenol First	Sevelamer HCl First
STARTED	77	75
COMPLETED	77	75
NOT COMPLETED	0	0

Period: Second Intervention

	Fosrenol First	Sevelamer HCl First
STARTED	77	75
COMPLETED	65	68
NOT COMPLETED	12	7
Adverse Event	5	2
Protocol Violation	4	1
Withdrawal by Subject	1	1
Kidney Transplant	1	1
Lack of Efficacy	0	1
Subject exceeded safety criteria	1	0
Subject moved	0	1

Baseline Characteristics

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Reporting Groups

	Description
Entire Study Population	No text entered.

Baseline Measures

	Entire Study Population
Number of Participants [units: participants]	182
Age [units: participants]
<=18 years	0
Between 18 and 65 years	140
>=65 years	42
Age [units: years] Mean ± Standard Deviation	55.5 ± 13.10
Gender [units: participants]
Female	80
Male	102
Region of Enrollment [units: participants]
United States	139
Puerto Rico	1
Germany	41
United Kingdom	1

Outcome Measures

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1. Primary:

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

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2. Secondary:

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

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3. Secondary:

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

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Measure Type	Secondary
Measure Title	Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks
Measure Description	No text entered.
Time Frame	Baseline and 4 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT

Reporting Groups

	Description
Fosrenol	Lanthanum carbonate
Sevelamer HCl	No text entered.

Measured Values

	Fosrenol	Sevelamer HCl
Number of Participants Analyzed [units: participants]	165	161
Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks [units: pg/mL] Mean ± Standard Error
Baseline	225.46 ± 11.094	225.46 ± 11.094
Endpoint	296.48 ± 17.412	291.18 ± 16.181

No statistical analysis provided for Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks

4. Secondary:

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

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Timothy Whitaker, MD
Organization: Shire
e-mail: twhitaker@shire.com

No publications provided

Responsible Party:	Shire Pharmaceutical ( Timothy Whitaker, M.D. )
Study ID Numbers:	SPD405-319
Study First Received:	February 27, 2007
Results First Received:	June 29, 2009
Last Updated:	October 1, 2009
ClinicalTrials.gov Identifier:	NCT00441545 History of Changes
Health Authority:	United States: Food and Drug Administration