Abstract: FR-PO1155
Long-Term Safety of Cinacalcet in Pediatric CKD Subjects on Dialysis
Session Information
- Pediatric Nephrology - I
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1600 Pediatric Nephrology
Authors
- Warady, Bradley A., Children's Mercy Kansas City , Kansas City, Missouri, United States
- Cheng, Sunfa, Amgen INC, Newbury Park, California, United States
- Wang, Fei, Amgen INC, Newbury Park, California, United States
- Stark, William W., Amgen INC, Newbury Park, California, United States
- Vondrak, Karel, University Hospital Prague-Motol, Prague 5, Czechia
Background
The calcimimetic cinacalcet is indicated for treatment (tx) of secondary hyperparathyroidism in adults with CKD on dialysis. Its use was evaluated in pediatric CKD subjects (subj) on dialysis in 2 parent trials: NCT01439867 (single arm; age 28d-<6y) and NCT02138838 (open-label; cinacalcet vs standard of care [SOC]; age 6-<18y). This phase 3, single-arm, open-label extension evaluated cinacalcet use in subj who completed the parent trials or were still on study at early parent trial termination.
Methods
This 32-week (W) (28 tx+4 follow-up) study assessed the safety of cinacalcet based on incidence of tx-emergent adverse events (TEAE) of interest (primary endpoint [EP]). Secondary EP included ≥30% mean iPTH reduction during W11+15 and 23+28, % mean iPTH change during W23+28 (each assessed only in SOC subj in NCT02138838), and ≥30% mean iPTH reduction and change in serum Ca and P during W23+28 (all subj). Cinacalcet subj in the parent study continued the same dose; SOC subj had iPTH ≥300pg/mL and Ca ≥8.8mg/dL, and received initial doses of 0.2mg/kg/d. Cinacalcet was titrated (up to 2.5mg/kg/d; ≤60mg/d [age <6y] or ≤180mg/d [age ≥6y]) to PTH ≥150-<300pg/mL and to maintain corrected Ca ≥8.4mg/dL or ionized Ca ≥1.05mmol/L for subj 6-<18y, and ≥9.0mg/dL or ionized Ca ≥1.13mmol/L for subj <2y.
Results
Of 28 enrolled subj, 5 discontinued tx due to renal transplant (n=2), parathyroidectomy, death unrelated to tx, and subj request (n=1 each). Mean (SD) age and cinacalcet exposure were 12.6 (3.9) y and 170 (52) d. 10 (40%) (W11-15) and 4 (18%) (W23-28) subj had ≥20% of doses withheld. 20 (71.4%) subj had ≥1 TEAE, most commonly hypocalcemia and pyrexia (n=3 each). Incidence of TEAE of interest were: hypocalcemia (n=5,17.9%), nervous system disorders excluding seizures (n=4,14.3%), hypersensitivity (n=2,7.1%), drug-related hepatic disorders, and fracture (n=1,3.6% each); none deemed serious. The proportion achieving ≥30% iPTH decrease is below. Median (Q1,Q3) iPTH change (prior SOC only) at W23+28 was 11.4% (-20.6, 27.3). Overall W23+28 median (Q1,Q3) serum Ca and P (mg/dL) change was -0.25 (-0.66, 0.10) and 0.06 (-0.94, 0.69).
Conclusion
There were no new/unexpected safety concerns in these pediatric CKD subj on dialysis.
| Prior SOC only (NCT0213883) Weeks 11 and 15 N=13 | Prior SOC only (NCT0213883) Weeks 23 and 28 N=13 | Total (NCT01439867 + NCT02138838) Weeks 23 and 28 N=28 | |
| n (%) achieving ≥30% reduction in mean iPTH | 4 (31%) | 3 (23%) | 4 (14%) |
Funding
- Commercial Support –