Comparing Absorption of Dietary Phosphorus When Administering FOSRENOL® or RENVELA® in Healthy Adult Volunteers

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00875017
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 4
• Actual Duration (Months): 1.9
• Patients Per Site Per Month: 16.6

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the absorption of dietary phosphorus following a single dose with lanthanum carbonate (1000mg) and a single dose of sevelamer carbonate (2400mg).

Condition or Disease	Intervention/Treatment	Phase
Kidney Failure, Chronic	Drug: Lanthanum Carbonate; Drug: Sevelamer	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Open-label, Phase I, One-dose, One-meal, Balance Study Comparing the Absorption of Dietary Phosphorus When Administering FOSRENOL® (Lanthanum Carbonate) or RENVELA® (Sevelamer Carbonate) in Healthy Adult Volunteers
• Actual Study Start Date: Apr 20, 2009
• Actual Primary Completion Date: Jun 16, 2009
• Actual Study Completion Date: Jun 16, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Meal + Lanthanum	Drug: Lanthanum Carbonate; 1 x 1000mg tablet; Other Names: Fosrenol
Active Comparator: Meal + Sevelamer	Drug: Sevelamer; 3 x 800mg tablets; Other Names: Renvela
No Intervention: Meal Only
No Intervention: Fasting

Outcome Measures

Primary Outcome Measures

1. Net Phosphorous Absorption [10 hours post-dose]

   Net phosphorous absorption (Lanthanum carbonate period) = phosphorous ingested in meal minus (Rectal effluent phosphorous after Lanthanum carbonate + meal minus Rectal effluent phosphorous after fasting). Net phosphorous absorption (Sevelamer Carbonate period) = Phosphorous ingested in meal minus (Rectal effluent phosphorous after Sevelamer carbonate + meal minus Rectal effluent phosphorous after fasting). Net phosphorous absorption (Meal only period) = Phosphorous ingested in meal minus (Rectal effluent phosphorous after meal only minus Rectal effluent phosphorous after fasting).

Secondary Outcome Measures

1. Net Phosphorous Binding [10 hours post-dose]

   Net Phosphorous Binding (Lanthanum carbonate period) = Rectal effluent phosphorous after Lanthanum carbonate + meal minus Rectal effluent phosphorous after meal only. Net Phosphorous Binding (Sevelamer carbonate period) = Rectal effluent phosphorous after Sevelamer carbonate + meal minus Rectal effluent phosphorous after meal only.

2. Net Calcium Absorption [10 hours post-dose]

   Net Calcium Absorption (Lanthanum carbonate period) = Calcium ingested in meal minus (Rectal effluent calcium after Lanthanum carbonate + meal minus Rectal effluent calcium after fasting). Net Calcium Absorption (Sevelamer Carbonate period) = Calcium ingested in meal minus (Rectal effluent calcium after Sevelamer carbonate + meal minus Rectal effluent calcium after fasting). Net Calcium Absorption (Meal only period) = Calcium ingested in meal minus (Rectal effluent calcium after meal only minus Rectal effluent calcium after fasting).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria

• Ability to provide informed consent to participate in the study.

• Healthy volunteers, age 19-45 inclusive.

• Subject must be willing to comply with applicable contraceptive requirements of the protocol

• Female subjects must have a negative pregnancy test

• Satisfactory medical assessment with no clinically significant or relevant abnormalities in medical history, physical examination, vital signs, ECG and laboratory evaluation.

• Body Mass Index (BMI) between 20.0 and 29.9kg/m² inclusive.

• Serum 1.25 dihydroxy vitamin D3 >30pg/mL.

• Ability to chew or swallow a dose of the investigational products and mannitol solution as prescribed in the protocol.

• Ability and willingness to fast for up to 24 hours.

Exclusion Criteria

• Current or recurrent disease that could affect the action, absorption or disposition of the investigational products utilized in this study, or could affect clinical or laboratory assessments.

• Current or relevant previous history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or study procedures.

• Significant illness within 2 weeks of the first dose of investigational product.

• Current use of any medication with the exception of hormonal replacement therapy or hormonal contraceptives within 14 days of first dose of investigational product.

• Known or suspected intolerance or hypersensitivity to the investigational product(s) or mannitol solution, closely related compounds or any of the stated ingredients.

• History of alcohol or other substance abuse within the last year.

• A positive screen for alcohol or drugs of abuse.

• Male subjects who consume more than 21 units of alcohol per week or three units per day. Female subjects who consume more than 14 units of alcohol per week or two units per day.

• A positive human immunodeficiency virus (HIV) antibody screen, Hepatitis B surface antigen (HBsAg) or Hepatitis C virus (HCV) antibody screen.

• Use of tobacco in any form or other nicotine-containing products in any form. Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.

• Routine consumption of more than two units of caffeine per day or subjects who experience caffeine withdrawal headaches.

• Donation of blood or blood products within 60 days prior to receiving the first dose of investigational product.

• Use of another investigational product within 30 days prior to receiving the first dose of investigational product or active enrolment in another drug or vaccine clinical study.

• An inability to follow a standardized diet and/or meal schedule, as required during the study.

• Substantial changes in eating habits within 30 days prior to receiving the first dose of investigational product, as assessed by the Investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	West Coast Clinical Trials	Cypress	California	United States	90630

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA recall information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00875017
• Other Study ID Numbers: SPD405-128
• First Posted: Apr 3, 2009
• Last Update Posted: Jun 15, 2021
• Last Verified: May 1, 2021

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

Study Results

Participant Flow

Pre-assignment Detail	Patients were randomized to one of 6 treatment sequences each of which consisted of four treatment periods separated by a 7-14 day washout period. In each of the first three treatment periods subjects received lanthanum carbonate 100mg +meal, sevelamer carbonate 2400mg+meal or meal. Subjects fasted in the fourth treatment period.

Arm/Group Title	Sequence 1	Sequence 2	Sequence 3	Sequence 4	Sequence 5	Sequence 6
Arm/Group Description	Lanthanum carbonate (1000 mg) + meal in first intervention period, washout, Sevelamer carbonate (2400 mg) + meal in second intervention period, washout, Meal only in third intervention period, washout, Fasting in fourth intervention period	Sevelamer carbonate (2400 mg) + meal in first intervention period, washout, Meal only in second intervention period, washout, Lanthanum carbonate (1000 mg) + meal in third intervention period, washout, Fasting in fourth intervention period	Meal only in first intervention period, washout, Lanthanum carbonate (1000 mg) + meal in second intervention period, washout, Sevelamer carbonate (2400 mg) + meal in third intervention period, washout, Fasting in fourth intervention period	Lanthanum carbonate (1000 mg) + meal in first intervention period, washout, Meal only in second intervention period, washout, Sevelamer carbonate (2400 mg) + meal in third intervention period, washout, Fasting in fourth intervention period	Sevelamer carbonate (2400 mg) + meal in first intervention period, washout, Lanthanum carbonate (1000 mg) + meal in second intervention period, washout, Meal only in third intervention period, washout, Fasting in fourth intervention period	Meal only in first intervention period, washout, Sevelamer carbonate (2400 mg) + meal in second intervention period, washout, Lanthanum carbonate (1000 mg) + meal in third intervention period, washout, Fasting in fourth intervention period
Period Title: First Intervention
STARTED	5	5	5	6	5	5
COMPLETED	3	5	4	5	4	5
NOT COMPLETED	2	0	1	1	1	0
Period Title: First Intervention
STARTED	3	5	4	5	4	5
COMPLETED	3	5	3	5	4	5
NOT COMPLETED	0	0	1	0	0	0
Period Title: First Intervention
STARTED	3	5	3	5	4	5
COMPLETED	3	5	3	4	4	5
NOT COMPLETED	0	0	0	1	0	0
Period Title: First Intervention
STARTED	3	5	3	4	4	5
COMPLETED	3	4	3	4	4	5
NOT COMPLETED	0	1	0	0	0	0
Period Title: First Intervention
STARTED	3	4	3	4	4	5
COMPLETED	3	3	2	4	4	5
NOT COMPLETED	0	1	1	0	0	0
Period Title: First Intervention
STARTED	3	3	2	4	4	5
COMPLETED	3	3	2	4	3	5
NOT COMPLETED	0	0	0	0	1	0
Period Title: First Intervention
STARTED	3	3	2	4	3	5
COMPLETED	3	3	2	4	3	4
NOT COMPLETED	0	0	0	0	0	1

Baseline Characteristics

Arm/Group Title	Sequence 1	Sequence 2	Sequence 3	Sequence 4	Sequence 5	Sequence 6	Total
Arm/Group Description	Lanthanum carbonate (1000 mg) + meal in first intervention period, washout, Sevelamer carbonate (2400 mg) + meal in second intervention period, washout, Meal only in third intervention period, washout, Fasting in fourth intervention period	Sevelamer carbonate (2400 mg) + meal in first intervention period, washout, Meal only in second intervention period, washout, Lanthanum carbonate (1000 mg) + meal in third intervention period, washout, Fasting in fourth intervention period	Meal only in first intervention period, washout, Lanthanum carbonate (1000 mg) + meal in second intervention period, washout, Sevelamer carbonate (2400 mg) + meal in third intervention period, washout, Fasting in fourth intervention period	Lanthanum carbonate (1000 mg) + meal in first intervention period, washout, Meal only in second intervention period, washout, Sevelamer carbonate (2400 mg) + meal in third intervention period, washout, Fasting in fourth intervention period	Sevelamer carbonate (2400 mg) + meal in first intervention period, washout, Lanthanum carbonate (1000 mg) + meal in second intervention period, washout, Meal only in third intervention period, washout, Fasting in fourth intervention period	Meal only in first intervention period, washout, Sevelamer carbonate (2400 mg) + meal in second intervention period, washout, Lanthanum carbonate (1000 mg) + meal in third intervention period, washout, Fasting in fourth intervention period	Total of all reporting groups
Overall Participants	3	5	5	5	5	5	28
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	5 100%	5 100%	5 100%	5 100%	5 100%	28 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.0 (9.54)	23.6 (2.07)	24.4 (3.85)	27.4 (9.71)	25.8 (5.45)	28.2 (6.38)	25.9 (6.06)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	1 20%	2 40%	2 40%	2 40%	8 28.6%
Male	2 66.7%	5 100%	4 80%	3 60%	3 60%	3 60%	20 71.4%
Region of Enrollment (Count of Participants)
United States	3 100%	5 100%	5 100%	5 100%	5 100%	5 100%	28 100%

Outcome Measures

1. Primary Outcome

Title	Net Phosphorous Absorption
Description	Net phosphorous absorption (Lanthanum carbonate period) = phosphorous ingested in meal minus (Rectal effluent phosphorous after Lanthanum carbonate + meal minus Rectal effluent phosphorous after fasting). Net phosphorous absorption (Sevelamer Carbonate period) = Phosphorous ingested in meal minus (Rectal effluent phosphorous after Sevelamer carbonate + meal minus Rectal effluent phosphorous after fasting). Net phosphorous absorption (Meal only period) = Phosphorous ingested in meal minus (Rectal effluent phosphorous after meal only minus Rectal effluent phosphorous after fasting).
Time Frame	10 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacodynamic Set (PD) consists of subjects who provided all rectal effluent collections and completed all treatment periods. Subjects who vomited during any of the treatment periods were excluded from the PD set.

Arm/Group Title	Lanthanum Carbonate	Sevelamer Carbonate	Meal Only
Arm/Group Description	A meal containing a known amount of phosphorous is ingested along with oral administration of the phosphorous binder, lanthanum carbonate. 10 hours post-dose, rectal effluent is collected and the amount of phosphorous is measured.	A meal containing a known amount of phosphorous is ingested along wuith oral administration of the phosphorous binder, sevelamer carbonate. 10 hours post-dose, rectal effluent is collected and the amount of phosphorous is measured.	A meal containing a known amount of phosphorous is ingested. No phosphorous binder is administered. 10 hours post-meal, rectal effluent is collected and the amount of phosphorous is measured.
Measure Participants	18	18	18
Least Squares Mean (Standard Error) [mg]	156.03 (14.161)	221.78 (14.112)	281.68 (14.112)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lanthanum Carbonate, Sevelamer Carbonate
	Comments	Net phosphorus absorption was analysed using a mixed linear effect model with fixed effects for sequence group, period and treatment group. Subject within sequence effect was included as a random effect.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-65.75
	Confidence Interval	() 95%; -96.01 to -35.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lanthanum Carbonate, Meal Only
	Comments	Net phosphorus absorption was analysed using a mixed linear effect model with fixed effects for sequence group, period and treatment group. Subject within sequence effect was included as a random effect.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-125.65
	Confidence Interval	() 95%; -155.91 to -95.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sevelamer Carbonate, Meal Only
	Comments	Net phosphorus absorption was analysed using a mixed linear effect model with fixed effects for sequence group, period and treatment group. Subject within sequence effect was included as a random effect.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-59.90
	Confidence Interval	() 95%; -89.87 to -29.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Net Phosphorous Binding
Description	Net Phosphorous Binding (Lanthanum carbonate period) = Rectal effluent phosphorous after Lanthanum carbonate + meal minus Rectal effluent phosphorous after meal only. Net Phosphorous Binding (Sevelamer carbonate period) = Rectal effluent phosphorous after Sevelamer carbonate + meal minus Rectal effluent phosphorous after meal only.
Time Frame	10 hours post-dose

Outcome Measure Data

Analysis Population Description

PD set

Arm/Group Title	Lanthanum Carbonate	Sevelamer Carbonate
Arm/Group Description	A meal containing a known amount of phosphorous is ingested along with oral administration of the phosphorous binder, lanthanum carbonate. 10 hours post-dose, rectal effluent is collected and the amount of phosphorous is measured.	A meal containing a known amount of phosphorous is ingested along with oral administration of the phosphorous binder, sevelamer carbonate. 10 hours post-dose, rectal effluent is collected and the amount of phosphorous is measured.
Measure Participants	18	18
Least Squares Mean (Standard Error) [mg]	135.05 (12.348)	63.15 (12.348)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lanthanum Carbonate, Sevelamer Carbonate
	Comments	Phosphorus binding was analysed using a mixed linear effect model with fixed effects for sequence group, period and treatment group. Subject within sequence effect was included as a random effect.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	71.90
	Confidence Interval	() 95%; 40.03 to 103.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Net Calcium Absorption
Description	Net Calcium Absorption (Lanthanum carbonate period) = Calcium ingested in meal minus (Rectal effluent calcium after Lanthanum carbonate + meal minus Rectal effluent calcium after fasting). Net Calcium Absorption (Sevelamer Carbonate period) = Calcium ingested in meal minus (Rectal effluent calcium after Sevelamer carbonate + meal minus Rectal effluent calcium after fasting). Net Calcium Absorption (Meal only period) = Calcium ingested in meal minus (Rectal effluent calcium after meal only minus Rectal effluent calcium after fasting).
Time Frame	10 hours post-dose

Outcome Measure Data

Analysis Population Description

PD set

Arm/Group Title	Lanthanum Carbonate	Sevelamer Carbonate	Meal Only
Arm/Group Description	A meal containing a known amount of calcium is ingested along with oral administration of the phosphorous binder, lanthanum carbonate. 10 hours post-dose, rectal effluent is collected and the amount of calcium is measured.	A meal containing a known amount of calcium is ingested along with oral administration of the phosphorous binder, sevelamer carbonate. 10 hours post-dose, rectal effluent is collected and the amount of calcium is measured.	A meal containing a known amount of calcium is ingested. No phosphorous binder is administered. 10 hours post-meal, rectal effluent is collected and the amount of calcium is measured.
Measure Participants	18	18	18
Least Squares Mean (Standard Error) [mg]	49.46 (10.480)	70.13 (10.450)	65.02 (10.450)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lanthanum Carbonate, Sevelamer Carbonate
	Comments	Net calcium absorption was analysed using a mixed linear effect model with fixed effects for sequence group, period and treatment group. Subject within sequence effect was included as a random effect.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-20.67
	Confidence Interval	() 95%; -41.22 to -0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lanthanum Carbonate, Meal Only
	Comments	Net calcium absorption was analysed using a mixed linear effect model with fixed effects for sequence group, period and treatment group. Subject within sequence effect was included as a random effect.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.133
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-15.56
	Confidence Interval	() 95%; -36.11 to 4.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sevelamer Carbonate, Meal Only
	Comments	Net calcium absorption was analysed using a mixed linear effect model with fixed effects for sequence group, period and treatment group. Subject within sequence effect was included as a random effect.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.612
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.11
	Confidence Interval	() 95%; -15.24 to 25.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	Due to the crossover design of the study, discontinuations during the course of the study will affect the number of subjects receiving each treatment. Therefore, the number of subjects for each treatment will be less than 28 (the total number of subjects in the Safety Set).
Arm/Group Title	Lanthanum Carbonate		Sevelamer Carbonate		Meal Only		Fasting
Arm/Group Description
All Cause Mortality
	Lanthanum Carbonate		Sevelamer Carbonate		Meal Only		Fasting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lanthanum Carbonate		Sevelamer Carbonate		Meal Only		Fasting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)		0/26 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Lanthanum Carbonate		Sevelamer Carbonate		Meal Only		Fasting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)		3/26 (11.5%)		3/20 (15%)
Gastrointestinal disorders
Vomiting	0/23 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	1/20 (5%)	1
Nervous system disorders
Dizziness	0/23 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	1/20 (5%)	1
Headache	0/23 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	2	0/20 (0%)	0
Skin and subcutaneous tissue disorders
Rash pruritic	0/23 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/20 (5%)	1

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.