Trial Outcomes & Findings for Comparing Absorption of Dietary Phosphorus When Administering FOSRENOL® or RENVELA® in Healthy Adult Volunteers (NCT NCT00875017)

Last Updated: 2021-06-15

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

31 participants

Primary outcome timeframe

10 hours post-dose

Results posted on

2021-06-15

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Sequence 1 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	Sequence 2 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	Sequence 3 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	Sequence 4 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	Sequence 5 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	Sequence 6 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
First Intervention STARTED	5	5	5	6	5	5
First Intervention COMPLETED	3	5	4	5	4	5
First Intervention NOT COMPLETED	2	0	1	1	1	0
Washout STARTED	3	3	2	4	4	5
Washout COMPLETED	3	3	2	4	3	5
Washout NOT COMPLETED	0	0	0	0	1	0
Second Intervention STARTED	3	5	3	5	4	5
Second Intervention COMPLETED	3	5	3	4	4	5
Second Intervention NOT COMPLETED	0	0	0	1	0	0
Third Intervention STARTED	3	4	3	4	4	5
Third Intervention COMPLETED	3	3	2	4	4	5
Third Intervention NOT COMPLETED	0	1	1	0	0	0
Fourth Intervention STARTED	3	3	2	4	3	5
Fourth Intervention COMPLETED	3	3	2	4	3	4
Fourth Intervention NOT COMPLETED	0	0	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1 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	Sequence 2 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	Sequence 3 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	Sequence 4 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	Sequence 5 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	Sequence 6 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
First Intervention Withdrawal by Subject	1	0	1	0	0	0
First Intervention Adverse Event	0	0	0	1	0	0
First Intervention Problems collecting rectal effluent	1	0	0	0	0	0
First Intervention Intolerance to nasogastric tube	0	0	0	0	1	0
Washout Problem collecting rectal effluent	0	0	1	0	0	0
Second Intervention Adverse Event	0	0	0	1	0	0
Washout Problems collecting rectal effluent	0	1	0	0	0	0
Third Intervention Adverse Event	0	1	1	0	0	0
Washout Withdrawal by Subject	0	0	0	0	1	0
Fourth Intervention Inability to comply with fasting	0	0	0	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence 1 n=3 Participants 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	Sequence 2 n=5 Participants 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	Sequence 3 n=5 Participants 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	Sequence 4 n=5 Participants 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	Sequence 5 n=5 Participants 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	Sequence 6 n=5 Participants 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 n=28 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	5 Participants n=21 Participants	5 Participants n=10 Participants	28 Participants n=115 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Continuous	26.0 years STANDARD_DEVIATION 9.54 • n=5 Participants	23.6 years STANDARD_DEVIATION 2.07 • n=7 Participants	24.4 years STANDARD_DEVIATION 3.85 • n=5 Participants	27.4 years STANDARD_DEVIATION 9.71 • n=4 Participants	25.8 years STANDARD_DEVIATION 5.45 • n=21 Participants	28.2 years STANDARD_DEVIATION 6.38 • n=10 Participants	25.9 years STANDARD_DEVIATION 6.06 • n=115 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=10 Participants	8 Participants n=115 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=10 Participants	20 Participants n=115 Participants
Region of Enrollment United States	3 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	5 Participants n=21 Participants	5 Participants n=10 Participants	28 Participants n=115 Participants

PRIMARY outcome

Timeframe: 10 hours post-dose

Population: 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.

Outcome measures

Outcome measures
Measure	Lanthanum Carbonate n=18 Participants 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.	Sevelamer Carbonate n=18 Participants 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.	Meal Only n=18 Participants 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.
Net Phosphorous Absorption	156.03 mg Standard Error 14.161	221.78 mg Standard Error 14.112	281.68 mg Standard Error 14.112

SECONDARY outcome

Timeframe: 10 hours post-dose

Population: PD set

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.

Outcome measures

Outcome measures
Measure	Lanthanum Carbonate n=18 Participants 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.	Sevelamer Carbonate n=18 Participants 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.	Meal Only 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.
Net Phosphorous Binding	135.05 mg Standard Error 12.348	63.15 mg Standard Error 12.348	—

SECONDARY outcome

Timeframe: 10 hours post-dose

Population: PD set

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).

Outcome measures

Outcome measures
Measure	Lanthanum Carbonate n=18 Participants 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.	Sevelamer Carbonate n=18 Participants 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.	Meal Only n=18 Participants 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.
Net Calcium Absorption	49.46 mg Standard Error 10.480	70.13 mg Standard Error 10.450	65.02 mg Standard Error 10.450

Adverse Events

Lanthanum Carbonate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sevelamer Carbonate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Meal Only

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Fasting

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lanthanum Carbonate n=23 participants at risk	Sevelamer Carbonate n=24 participants at risk	Meal Only n=26 participants at risk	Fasting n=20 participants at risk
Gastrointestinal disorders Vomiting	0.00% 0/23 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).	0.00% 0/24 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).	3.8% 1/26 • Number of events 1 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).	5.0% 1/20 • Number of events 1 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).
Nervous system disorders Dizziness	0.00% 0/23 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).	0.00% 0/24 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).	3.8% 1/26 • Number of events 1 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).	5.0% 1/20 • Number of events 1 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).
Nervous system disorders Headache	0.00% 0/23 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).	0.00% 0/24 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).	7.7% 2/26 • Number of events 2 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).	0.00% 0/20 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).
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/23 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).	0.00% 0/24 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).	0.00% 0/26 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).	5.0% 1/20 • Number of events 1 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).

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER