Abstract: FR-PO965
An Integrated Analysis of Safety and Tolerability of Etelcalcetide in Adult Patients on Hemodialysis (HD) with Secondary Hyperparathyroidism (SHPT)
Session Information
- Patient Safety
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Patient Safety
- 1501 Patient Safety
Authors
- Block, Geoffrey A., Denver Nephrology, Denver, Colorado, United States
- Chertow, Glenn Matthew, Stanford University School of Medicine, Palo Alto, California, United States
- Sullivan, John T, Amgen, Thousand Oaks, California, United States
- Deng, Hongjie, Amgen Inc. , Thousand Oaks, California, United States
- Mather, Omar, Amgen Inc, Thousand Oaks, California, United States
- Tomlin, Holly, Amgen Inc. , Thousand Oaks, California, United States
- Serenko, Michael, Amgen, Thousand Oaks, California, United States
Background
Etelcalcetide (ETL) is a novel, IV calcimimetic for the treatment of SHPT in patients on HD. Here, the safety profile of ETL is summarized.
Methods
Safety was assessed by the nature, frequency, and severity of treatment-emergent adverse events (AEs) and changes in lab parameters in the integrated datasets of two 26-week randomized, placebo (PBO)-controlled (PC) studies, a 26-week randomized active-controlled (AC with cinacalcet [CIN]) study, and 2 single-arm open-label extension (OLE) studies. The ETL starting dose was 5 mg 3 times/week (TIW) at the end of HD. Depending on serum PTH and Ca values, the dose could be increased by 2.5 or 5 mg at 4-week intervals to a maximum dose of 15 mg TIW.
Results
841 patients received ETL in the PC (n=503) and AC (n=338) studies and 1289 in the OLE studies for up to 3.4 yr. In the combined dataset of PC studies, common (≥5%) AEs occurring in the ETL group with a ≥1% greater frequency than PBO were blood Ca decrease (63.8% vs 10.1%), muscle spasms (11.5% vs 6.6%), diarrhea (10.7% vs 8.6%), nausea (10.7% vs 6.2%), vomiting (8.9% vs 5.1%), headache (7.6% vs 6.0%), and symptomatic hypocalcaemia (7.0 vs 0.2%). Rates of AEs of interest were similar between ETL and PBO for convulsions (0.8% vs 1.0%), fractures (1.6% vs 2.9%), hypersensitivity (4.4% vs 3.7%), infusion reaction (5.8% vs 5.7%), ventricular tachyarrhythmia (0.4% vs 0.8%), and GI bleeding (2.0% and 2.1%); a small numerical difference was noted in the rate of adjudicated cardiac failure (2.2% vs 1.2%). More patients in the ETL vs PBO groups experienced hypophosphatemia (1.4% vs 0.4%). ETL had no clinically significant effects on blood pressure, heart rate, weight, or hematology lab parameters. No clinically significant differences were observed in the safety profiles of ETL and CIN in the AC study. No new safety signals were identified with long-term ETL exposure in the OLE studies.
Conclusion
Consistent with its mechanism of action, the most important risks associated with ETL were serum Ca reductions and hypocalcemia-related AEs. Integrated safety assessment of ETL across both controlled clinical trials and OLE studies showed an overall favorable risk/benefit profile with no unexpected safety signals.
Funding
- Commercial Support –