Table 4.
Titration schema and dosing decisions used in Amgen-supported clinical trials 20070208 and 20130356
| Dry weight (kg) | Starting dose (mg)a,b | Possible dose titration steps | |||||
|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | ||
| 12.5 to 14 | 2.5 | 5 | 10 | 15 | 30 | 30 | 30 |
| > 14 to 21 | 2.5 | 5 | 10 | 15 | 30 | 60 | 60 |
| > 21 to 25 | 2.5 | 5 | 10 | 15 | 30 | 60 | 90 |
| > 25 to 28 | 5 | 10 | 15 | 30 | 60 | 90 | 90 |
| > 28 to 49 | 5 | 10 | 15 | 30 | 60 | 90 | 120 |
| > 49 to <75 | 10 | 15 | 30 | 60 | 90 | 120 | 180 |
| ≥ 75 | 15 | 30 | 60 | 90 | 120 | 180 | 180 |
| Criteria for dosing decisions | Study 20070208c | Study 20130356 | |||||
| Dose maintenance |
• PTH: ≥ 150 to < 300 pg/mL • Subject did not meet any criteria for dose reduction or withholding of dose. |
• PTH ≥ 150 to < 300 pg/mL • Subject did not meet any criteria for dose reduction or withholding of dose. |
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| Dose reduction |
• PTH ≥ 100 to < 150 pg/mL • cCa ≥ 8.0 to < 8.4 mg/dL • Subject had AE that required dose reduction. • Subject did not meet any criteria for withholding of dose. |
• PTH ≥ 100 to < 150 pg/mL • cCa ≥ 8.0 to < 8.4 mg/dL • iCa ≥ 1.00 to < 1.05 mmol/L • Subject did not meet any criteria for withholding of dose. |
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| Dose withholding |
• PTH < 100 pg/mL • cCa < 8.0 mg/dL • Symptoms of hypocalcemia. • Subject had AE that required withholding of dose. |
• PTH < 100 pg/mL • cCa < 8.0 mg/dL (via either a central or local assessmentd) • iCa < 1.00 mmol/L • Symptoms of hypocalcemia • Subject had AE that required withholding of dose. • Temporary administration of concomitant medications (CYP3A4 inhibitors or CYP2D6 substrates) that are known to prolong the QTc interval. |
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Dose increases were allowed every 4 weeks. The dose was increased if the plasma PTH was ≥ 300 pg/mL, provided the subject did not meet any criteria for dose maintenance, dose reduction, or dose withholding, and the subject had not reached the maximum allowed dose. In Study 20130356, the dose of cinacalcet was also not increased in subjects who were determined to be noncompliant according to protocol-specified definitions
aIn Study 20070208, the starting dose was ≤ 0.2 mg/kg/day. bIn Study 20130356, the starting dose was 0.2 mg/kg/day rounded down to the nearest protocol-specified dose. cFollowing the partial hold (prior to study termination), Study 20070208 protocol was amended utilizing the dry weight-based dosing schema for all dose adjustments during the double-blind phase, and the week 30 dry weight for all dose adjustments during the open-label phase. dTotal calcium concentration
AE, adverse event; cCa, corrected serum calcium; CYP, cytochrome; iCa, ionized calcium; QTc interval, corrected QT interval; PTH, parathyroid hormone