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 Rayaldee arms and were unchanged in the placebo arms (P<0.001).
Mean Serum Total 25(OH)D, ng/mL | ||||
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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
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 patients in the placebo arm.
Mean Plasma iPTH, pg/ml | ||||
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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 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 | ||
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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*
Study 1 (N=213) | Study 2 (N=216) | |
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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 had recieved placebo transitioned to Rayaldee.
Mean Serum Calcium, mg/dL | ||||
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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 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 |
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Anemia |
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Nasopharyngitis |
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Blood creatinine increased |
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Dyspnea |
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Cough |
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Cardiac failure congestive |
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Constipation |
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Bronchitis |
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Hyperkalemia |
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Osteoarthritis |
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Hyperuricemia |
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Contusion |
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Pneumonia |
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Chronic obstructive pulmonary disease |
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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.