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Clinical Information

Rayaldee helped significantly more patients with stage 3 or 4 chronic kidney disease reduce intact parathyroid hormone (iPTH) by ≥30% from baseline and increase 25(OH)D to adequate levels (≥30 ng/mL), compared with placebo.1

Rayaldee significantly increased 25(OH)D levels1

Rayaldee significantly increased 25(OH)D levels1

Mean 25(OH)D levels over time in clinical trials1*

In clinical trials 1 and 2, mean serum 25(OH)D levels increased gradually over 26 weeks in the treatment arms and was unchanged in the placebo arms (P<0.001).

In clinical trials 1 and 2, mean serum 25(OH)D levels increased gradually over 26 weeks in the Rayaldee arms and were unchanged in the placebo arms (P<0.001).

Mean Serum Total 25(OH)D, ng/mL
Week of treatment Study 1: Rayaldee Arm Study 2: Rayaldee Arm Study 1: Placebo Arm Study 2: Placebo Arm
0 19.846377 19.621849 19.252688 19.269444
4 33.315789 34.915254 19.016667 18.416667
8 40.695652 43.228814 19.290323 19.711864
10 42.424528 45.468468 17.982759 18.576923
12 45.504348 48.177966 18.193548 18.758621
16 57.823009 58.794872 17.786885 18.983333
20 65.04386 65.82906 17.66129 19.383333
22 66.407407 67.06422 17.912281 19.578947
24 68.473214 67.324786 18.137931 19.372881
26 67.773913 69.222222 17.393443 19.982456

Increased 25(OH)D levels were associated with corresponding increases in 1,25D levels2

Patients achieving target 25(OH)D levels (≥30 ng/mL) at week 261

In clinical trial 1, 80% of patients in the treatment arm achieved target 25(OH)D levels of ≥30 ng/mL at week 26 versus 3% of patients in the placebo arm. In clinical trial 2, 83% of patients in the treatment arm achieved target 25(OH)D levels of ≥30 ng/mL at week 26 versus 7% of patients in the placebo arm.

Average steady-state 25(OH)D levels ≥50 ng/mL

In clinical trial 1, 80% of patients in the treatment arm achieved target 25(OH)D levels of ≥30 ng/mL at week 26 versus 3% of patients in the placebo arm. In clinical trial 2, 83% of patients in the treatment arm achieved target 25(OH)D levels of ≥30 ng/mL at week 26 versus 7% of patients in the placebo arm.

Rayaldee effectively reduced intact parathyroid hormone1*

Rayaldee effectively reduced intact parathyroid hormone1*

Mean iPTH levels over time in clinical trials*

In both clinical trials, spanning 26 weeks, iPTH declined in patients in the treatment arm. iPTH did not decline in patient in the placebo arm.

In both clinical trials, spanning 26 weeks, iPTH declined in patients in the treatment arm. iPTH did not decline in patients in the placebo arm.

Mean Plasma iPTH, pg/ml
Week of treatment Study 1: Rayaldee Arm Study 2: Rayaldee Arm Study 1: Placebo Arm Study 2: Placebo Arm
0 144.43 142.9 136.91 153.91
4 134.09 128.43 133.46 152.59
8 126.83 124.74 142.28 160.55
10 123.78 122.88 142.42 167.31
12 122.95 122.48 140.47 169.05
16 120.86 113.75 144.32 162.83
20 109.29 110.14 145.74 155.42
22 107.44 121.9 148.42 148.07
24 105.04 115.56 139.82 162.33
26 113.25 110.88 148.72 166.4

iPTH levels declined over time with Rayaldee compared to placebo treatment (P<0.001)1*

Mean iPTH change from baseline1

In both clinical trials, which spanned 26 weeks, the mean iPTH declined from baseline patients in the treatment arm. The mean iPTH did not change from baseline in patient in the placebo arm. P<0.001.

In both clinical trials, which spanned 26 weeks, the mean iPTH declined from baseline in patients in the treatment arm. The mean iPTH did not change from baseline in patients in the placebo arm. P<0.001.

Percent Change From Baseline
Week of treatment Rayaldee Arm Placebo Arm
0 0 0
4 -8.04 -1.4
8 -11.81 4.59
10 -12.95 4.3
12 -13.62 3.26
16 -18.01 5.2
20 -22.84 2.4
22 -19.9 1.67
24 -23.64 3.82
26 -21.99 9.43

Patients achieving iPTH response
(≥30% change from baseline to end of trial)1*

Patients achieving iPTH response chart
Study 1 (N=213) Study 2 (N=216)
Rayaldee arm (% of patients) 33 34
Placebo arm (% of patients) 8 7

The effect of Rayaldee on serum calcium and phosphorus was similar to placebo1*

The effect of Rayaldee on serum calcium and phosphorus was similar to placebo1*

Mean serum calcium over time in clinical trials1†

In clinical trials 1 and 2, mean serum calcium levels did not significantly change compared to placebo over 26 weeks of treatment. There was not a significant difference in serum calcium levels during the extension trial which spanned weeks 26-52 and in which patients who were on placebo transitioned to Rayaldee.

In clinical trials 1 and 2, mean serum calcium levels did not significantly change compared to placebo over 26 weeks of treatment. There was not a significant difference in serum calcium levels during the extension trial, which spanned weeks 26-52 and in which patients who had recieved placebo transitioned to Rayaldee.

Mean Serum Calcium, mg/dL
Week of treatment Study 1: Rayaldee Arm Study 2: Rayaldee Arm Study 1: Placebo Arm Study 2: Placebo Arm
0 9.18826 9.23754 9.23898 9.25583
4 9.11304 9.15932 9.20333 9.09138
8 9.18596 9.28151 9.14194 9.12833
10 9.18302 9.28364 9.21034 9.20385
12 9.34912 9.37863 9.30968 9.30172
16 9.30088 9.34492 9.22333 9.19667
20 9.36283 9.41111 9.28226 9.2931
22 9.31101 9.32547 9.25179 9.31071
24 9.37117 9.46842 9.27167 9.31186
26 9.46 9.54017 9.34262 9.35614

Participants in Study 2 were offered the opportunity to continue into an extension study. Patients who had been in the Rayaldee arm remained on study medication. Patients who had been in the placebo arm started treatment with Rayaldee.

Mean Serum Calcium, mg/dL
Week of treatment Study 2 Extension: Rayaldee Continuation Study 2 Extension: Placebo to Rayaldee
26 9.47879 9.34382
30 9.40061 9.28764
34 9.38765 9.24333
36 9.39878 9.34886
38 9.50183 9.39778
42 9.55565 9.47614
46 9.4672 9.46444
50 9.55403 9.44494
52 9.57561 9.49663

Mean serum phosphorus over time in clinical trials1†

In clinical trials 1 and 2, mean serum phosphorus levels did not significantly change compared to placebo over 26 weeks of treatment. There was not a significant difference in serum phosphorus levels during the extension trial which spanned weeks 26-52 and in which patients who were on placebo transitioned to Rayaldee.

In clinical trials 1 and 2, mean serum calcium levels did not significantly change compared to placebo over 26 weeks of treatment. There was not a significant difference in serum calcium levels during the extension trial which spanned weeks 26-52 and in which patients who were on placebo transitioned to Rayaldee.

Mean Serum Phosphorus, pg/ml
Week of treatment Study 1: Rayaldee Arm Study 2: Rayaldee Arm Study 1: Placebo Arm Study 2: Placebo Arm
0 3.72188 3.78333 3.80054 3.63167
4 3.8287 3.86134 3.81667 3.78833
8 3.81053 3.97479 3.90161 3.84667
10 3.90566 3.91532 3.89828 3.78462
12 3.84561 3.88291 3.8129 3.82203
16 3.87456 4.0161 3.90333 3.735
20 3.84779 4.02712 3.82581 3.76552
22 3.89908 4.01963 3.92281 3.74464
24 3.9 4.01316 4.01667 3.79322
26 3.89565 4.02991 3.85574 3.71404

Participants in Study 2 were offered the opportunity to continue into an extension study. Patients who had been in the Rayaldee arm remained on study medication. Patients who had been in the placebo arm started treatment with Rayaldee.

Mean Serum Phosphorus, mg/dL
Week of treatment Study 2 Extension: Rayaldee Continuation Study 2 Extension: Placebo to Rayaldee
26 3.99879 3.8618
30 3.97378 3.85111
34 3.95366 3.82444
36 3.97455 3.90909
38 4.00427 3.87556
42 3.9896 3.91444
46 3.8928 3.85889
50 4.0216 3.96222
52 3.89758 3.9809
*

Patients randomized to Rayaldee had a greater mean (SE) increase in calcium and phosphorus than patients randomized to placebo (Calcium: Rayaldee 0.2 [0.02] mg/dL versus placebo 0.1 [0.03] mg/dL [P<0.001]; Phosphorus: Rayaldee 0.2 [0.03] mg/dL versus placebo 0.1 [0.04] mg/dL). A total of 4.2% of Rayaldee-treated subjects and 2.1% of placebo-treated subjects had at least 1 elevation in calcium above the upper limit of normal (10.5 mg/dL). A total of 45% of Rayaldee-treated subjects and 44% of placebo-treated subjects had at least 1 elevation in phosphorus above the upper limit of normal (4.5 mg/dL).1

Clinical trials have demonstrated a safety profile for Rayaldee similar to placebo1,2

Clinical trials have demonstrated a safety profile for Rayaldee similar to placebo1,2

Common Adverse Reactions in Phase 3 Placebo-Controlled Trials Reported in ≥1.4% of Rayaldee-Treated Subjects

Adverse Reactions
Placebo (n=144)
Rayaldee (n=285)
%
%
Anemia
3.5
4.9
Nasopharyngitis
2.8
4.9
Blood creatinine increased
1.4
4.9
Dyspnea
2.8
4.2
Cough
2.1
3.5
Cardiac failure congestive
0.7
3.5
Constipation
2.8
3.2
Bronchitis
0.7
2.8
Hyperkalemia
0.7
2.5
Osteoarthritis
0.7
2.1
Hyperuricemia
0.7
1.8
Contusion
0.0
1.8
Pneumonia
0.7
1.4
Chronic obstructive pulmonary disease
0.0
1.4

Abbreviations
1,25D=1,25-dihydroxyvitamin D; 25(OH)D=25-hydroxyvitamin D; CKD=chronic kidney disease; CV=cardiovascular; iPTH=intact parathyroid hormone; SHPT=secondary hyperparathyroidism.

References: 1. Sprague SM, Crawford PW, Melnick JZ, et al. Use of extended-release calcifediol to treat secondary hyperparathyroidism in stages 3 and 4 chronic kidney disease. Am J Nephrol. 2016;44(4):316-325. 2. Rayaldee [package insert]. Miami, FL: OPKO Pharmaceuticals, LLC; December 2019.

Important Safety Information

Hypercalcemia: Excessive administration of vitamin D compounds, including Rayaldee, can cause hypercalcemia and hypercalciuria. Severe hypercalcemia due to substantial overdosage of vitamin D and its metabolites may require emergency attention. Patients should be informed about the symptoms of elevated calcium.
Digitalis toxicity: Potentiated by hypercalcemia of any cause. Monitor serum calcium and signs and symptoms of digitalis toxicity more frequently when initiating or adjusting the dose of Rayaldee.
Adynamic Bone Disease: Monitor for abnormally low levels of intact parathyroid hormone (iPTH) levels when using Rayaldee, and adjust dose if needed.
The most common adverse reactions (≥3% and more frequent than placebo) were anemia, nasopharyngitis, increased blood creatinine, dyspnea, cough, congestive heart failure and constipation.
Care should be taken while dosing Rayaldee with cytochrome P450 inhibitors, thiazides, cholestyramine or drugs stimulating microsomal hydroxylation due to the potential for drug interactions.
Serum calcium should be below 9.8 mg/dL before initiating treatment.
Monitor serum calcium, phosphorus, 25-hydroxyvitamin D and iPTH 3 months after starting therapy or changing dose.

Indication and Limitations of Use

Rayaldee® (calcifediol) extended-release 30 mcg capsules is indicated for the treatment of secondary hyperparathyroidism in adults with stage 3 or 4 chronic kidney disease and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. Rayaldee is not indicated in patients with stage 5 chronic kidney disease or end-stage renal disease on dialysis.

Important Safety Information

Hypercalcemia: Excessive administration of vitamin D compounds, including Rayaldee, can cause hypercalcemia and hypercalciuria. Severe hypercalcemia due to substantial overdosage of vitamin D and its metabolites may require emergency attention. Patients should be informed about the symptoms of elevated calcium.
Digitalis toxicity: Potentiated by hypercalcemia of any cause. Monitor serum calcium and signs and symptoms of digitalis toxicity more frequently when initiating or adjusting the dose of Rayaldee.
Adynamic Bone Disease: Monitor for abnormally low levels of intact parathyroid hormone (iPTH) levels when using Rayaldee, and adjust dose if needed.
The most common adverse reactions (≥3% and more frequent than placebo) were anemia, nasopharyngitis, increased blood creatinine, dyspnea, cough, congestive heart failure and constipation.
Care should be taken while dosing Rayaldee with cytochrome P450 inhibitors, thiazides, cholestyramine or drugs stimulating microsomal hydroxylation due to the potential for drug interactions.
Serum calcium should be below 9.8 mg/dL before initiating treatment.
Monitor serum calcium, phosphorus, 25-hydroxyvitamin D and iPTH 3 months after starting therapy or changing dose.