Lanthanum Carbonate Reduces Urine Phosphorus Excretion: Evidence of High-Capacity Phosphate Binding

Figures & data

Table 1. Summary of studies of lanthanum carbonate (LC).

Study	Description	n	Phosphorus intake (mg/day)	Treatments (doses)	Details
Study 1	Parallel-group,dose-rangingstudy	70	∼2000	LC^a • 750 mg/day • 1500 mg/day • 3000 mg/day • 4500 mg/day • 6000 mg/day Control	• Taken with 200 mL water • Three times daily for 6 days, with one dosegiven on the morning of day 7 • Average 24-h urinary phosphorus excretionwas calculated for the 3 days before dosing(baseline) and the final 3 days of treatment
Study 2	Three-way crossover,pharmacodynamicequivalence study	56	Standard	LC • 3000 mg/day^a ○ 4 × 250 mg ○ 2 × 500 mg ○ 1 × 1000 mg All three times daily	• Taken with 400 mL water • Three times daily for 3 days, with one dosegiven on the morning of day 4 • At least 14 days washout was allowedbetween treatment periods • Average 24-h urinary phosphorus excretionwas calculated for the day before dosing(baseline) and the 3-day treatment periods
Study 3	Two-way crossover,alternativeformulation study	52	∼1300	LC • 3000 mg/day^a ○ 4 × 250 mg ○1 × 1000 mg newformulation ˆ All three times daily	• Taken with 200 mL water • Three times daily for 3 days, with one dosegiven on the morning of day 4 • At least 14 days washout between treatmentperiods • Average 24-h urinary phosphorus excretionwas calculated for the 2 days before dosing(baseline) and the 3-day treatment periods
Study 4	Two-way crossover,optimizedformulation study	57	∼1300	LC • 3000 mg/day^a (4 × 250 mgthree times daily) ○ Optimized formulation(batch A) ○ Alternative formulation(batch B)	• Taken with 240 mL water • Three times daily for 3 days, with one dosegiven on the morning of day 4 • At least 10 days washout between treatmentperiods • Average 24-h urinary phosphorus excretionwas calculated for the 2 days before dosing(baseline) and the 3-day treatment periods
Study 5	Parallel-group,placebo-controlledstudy	9	∼1200	LC • 3000 mg/day^a ○ 4 × 250 mg, three times daily • Matching placebo	• Taken with 150 mL water • Three times daily for 5 days • 24-h urinary phosphorus excretion wascalculated on the day before dosing(baseline) and compared with that on thefinal day of treatment

Note: ^aElemental lanthanum.

Table 2. Baseline characteristics for study 1 at total doses of 750, 1500, 3000, 4500, and 6000 mg lanthanum per day and control.

Parameter	750 mg/day	1500 mg/day	3000 mg/day	4500 mg/day	6000 mg/day	Control
n	10	10	10	10	10	10
Age, mean ± SD (range) (years)	26.1 ± 5.7(20–38)	27.2 ± 7.4(18–42)	25.4 ± 5.2(20–37)	23.9 ± 3.0(20–28)	23.4 ± 3.4(20–31)	25.9 ± 3.8(19–31)
Gender
Male	6 (60.0)	7 (70.0)	6 (60.0)	1 (10.0)	2 (20.0)	4 (40.0)
Female	4 (40.0)	3 (30.0)	4 (40.0)	9 (90.0)	8 (80.0)	6 (60.0)
Race
Caucasian	9 (90.0)	9 (90.0)	9 (90.0)	9 (90.0)	8 (80.0)	10 (100.0)
Black	0 (0)	0 (0)	0 (0)	1 (10.0)	0 (0)	0 (0)
Asian	1 (10.0)	1 (10.0)	1 (10.0)	0 (0)	1 (10.0)	0 (0)
Other	0 (0)	0 (0)	0 (0)	0 (0)	1 (10.0)	0 (0)
Weight, mean ± SD (range) (kg)	73.5 ± 8.3(60–83)	70.8 ± 13.9(51–93)	72.3 ± 12.6(54–91)	69.8 ± 10.7(56–85)	63.8 ± 9.6(54–81)	68.9 ± 6.5(56–76)
Serum phosphorus, mean ± SD (range) (mg/dL)	4.1 ± 0.3(3.7–5.0)	3.9 ± 0.4(3.4–4.3)	4.1 ± 0.4(3.7–4.6)	4.1 ± 0.5(3.7–5.0)	4.1 ± 0.5(3.4–5.0)	3.7 ± 0.4(3.4–4.6)
Serum calcium, mean ± SD (range) (mg/dL)	9.8 ± 0.4(9.2–10.4)	9.8 ± 0.2(9.6–10.0)	9.9 ± 0.2(9.6–10.4)	9.7 ± 0.3(9.2–10.0)	9.7 ± 0.2(9.6–10.0)	9.9 ± 0.2(9.6–10.0)

Notes: Data are presented as n (%), unless otherwise stated. Data relate to the safety population (with the exception of serum phosphorus and calcium, which are from the pharmacodynamic population) in all study groups.

Table 3. Baseline characteristics with lanthanum carbonate (LC) at a dose of 3000 mg/day of elemental lanthanum.

	Study
Parameter	Study 1	Study 2	Study 3^a	Study 4	Study 5
n	10	56	52	57	6
Age, mean ± SD (range) (years)	25.4 ± 5.2 (20–37)	25.2 ± 5.0 (18–40)	23.3 ± 3.2(18–31)	29.2 ± 10.8 (18–55)	23.3 ± 1.8 (21–26)
Gender
Male	6 (60.0)	27 (48.2)	25 (48.1)	37 (64.9)	6 (100)
Female	4 (40.0)	29 (51.8)	27 (51.9)	20 (35.1)	–
Race
Caucasian	9 (90.0)	54 (96.4)	46 (88.5)	12 (21.1)	–
Black	0 (0)	0 (0)	3 (5.8)	9 (15.8)	–
Asian	1 (10.0)	1 (1.8)	1 (1.9)	8 (14.0)	6 (100)
Other	0 (0)	1 (1.8)	2 (3.8)	28 (49.1)	–
Weight, mean ± SD (range) (kg)	72.3 ± 12.6 (54–92)	68.4 ± 10.8 (50–95)	67.2 ± 9.0(47–95)	72.6 ± 12.4 (47.2–106.8)	60.2 ± 6.5 (54–72)
Serum creatinine, mean ± SD (range) (mg/dL)	Not recorded	0.91 ± 0.11 (0.6–0.9)	A: 0.82 ± 0.11 (0.7–1.0) B: 0.84 ± 0.15 (0.6–1.1)	0.95 ± 0.23 (0.5–1.8)	1.03 ± 0.08 (1.0–1.2)
Serum phosphorus, mean ± SD (range) (mg/dL)	4.1 ± 0.4 (3.7–4.6)	3.6 ± 0.5 (2.5–4.6)	A: 3.1 ± 0.4 (2.2–4.0) B: 3.1 ± 0.5 (1.5–4.0)	3.6 ± 0.5 (2.5–5.0)	3.7 ± 0.3 (3.3–4.2)
Serum calcium, mean ± SD (range) (mg/dL)	9.9 ± 0.2 (9.6–10.4)	9.9 ± 0.4 (9.2–10.8)	A: 10.1 ± 0.3 (9.6–10.8) B: 10.0 ± 0.4 (9.2–10.8)	9.7 ± 0.3 (8.6–10.4)	9.1 ± 0.3 (8.7–9.3)

Notes: Data are presented as n (%), unless otherwise stated. Data relate to the safety population in all studies with the exception of phosphorus and calcium data for study 1; studies 2, 3, and 4 were crossover studies; study 1 only included patients receiving a daily dose of 3000 mg LC; and study 5 only included patients receiving LC.

^aPatients in arm A received 4 × 250 mg LC tablets first, those in arm B received 1 × 1000 mg LC tablet first.

Figure 1. Mean ± SD reduction from baseline in average daily urinary phosphorus excretion at different doses of lanthanum carbonate (study 1).

Table 4. Reduction in 24-h urinary phosphorus excretion from baseline with lanthanum carbonate (LC) at a dose of 3000 mg/day of elemental lanthanum.

	Urinary phosphorus excretion, mg/day (mmol/day)
Study and formulation(all given three times daily)	At baseline	At end point	Reduction from baseline
Study 1 (n = 9)
1 × 1000 mg tablet	992 ± 253 (32.0 ± 8.2)	662 ± 154 (21.4 ± 5.0)	329 ± 276 (10.6 ± 8.9)
Study 2 (n = 47)
4 × 250 mg tablets	592 ± 233 (19.1 ± 7.5)	353 ± 133 (11.4 ± 4.3)	239 ± 183 (7.7 ± 5.9)
2 × 500 mg tablets	663 ± 252 (21.4 ± 8.1)	370 ± 164 (11.9 ± 5.3)	294 ± 177 (9.5 ± 5.7)
1 × 1000 mg tablet	674 ± 310 (21.8 ± 10.0)	356 ± 144 (11.5 ± 4.6)	318 ± 294 (10.3 ± 9.5)
Study 3 (n = 48)
4 × 250 mg tablets	637 ± 195 (20.6 ± 6.3)	393 ± 130 (12.7 ± 4.2)	244 ± 164 (7.9 ± 5.3)
1 × 1000 mg tablet	646 ± 167 (20.8 ± 5.4)	410 ± 142 (13.2 ± 4.6)	236 ± 167 (7.6 ± 5.4)
Study 4 (n = 33)
Batch A (4 × 250 mg tablets)	952 ± 155 (30.7 ± 5.0)	643 ± 116 (20.7 ± 3.7)	309 ± 149 (10.0 ± 4.8)
Batch B (4 × 250 mg tablets)	921 ± 177 (29.7 ± 5.7)	641 ± 143 (20.7 ± 4.6)	279 ± 168 (9.0 ± 5.4)
Study 5 (n = 6)
4 × 250 mg tablets	680 ± 211 (21.9 ± 6.8)	212 ± 99 (6.8 ± 3.2)	468 ± 167 (15.1 ± 5.4)

Notes: Data relate to the pharmacodynamic populations; studies 2, 3, and 4 were crossover studies; study 1 only included patients receiving a daily dose of 3000 mg LC; and study 5 only included patients receiving LC. In study 4, batch A: optimized formulation; batch B: alternative formulation. Data are mean ± SD.