Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab

We evaluated the pharmacokinetics, pharmacodynamics, and safety of a single subcutaneous dose of romosozumab 210 mg, a monoclonal antibody against sclerostin, in an open‐label, parallel‐group study in participants with severe (stage 4) renal impairment (RI; n = 8) or end‐stage renal disease requirin...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2022-09, Vol.62 (9), p.1132-1141
Main Authors: Hsu, Cheng‐Pang, Maddox, Judy, Block, Geoffrey, Bartley, Yessenia, Yu, Zhigang
Format: Article
Language:English
Subjects:
biologics
Calcium (blood)
clinical trial
Hemodialysis
Hypocalcemia
Kidney diseases
Monoclonal antibodies
Parathyroid hormone
Pharmacodynamics
Pharmacokinetics
pharmacokinetics and drug metabolism
Procollagen
renal disease
Renal function
SOST protein
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Summary:We evaluated the pharmacokinetics, pharmacodynamics, and safety of a single subcutaneous dose of romosozumab 210 mg, a monoclonal antibody against sclerostin, in an open‐label, parallel‐group study in participants with severe (stage 4) renal impairment (RI; n = 8) or end‐stage renal disease requiring hemodialysis (ESRD‐RH; n = 8), or healthy participants with normal renal function (n = 8). Compared with the group with normal renal function, the mean romosozumab exposure was 31% and 43% higher as measured by maximum observed serum concentration and area under the concentration‐time curve, respectively, in the severe RI group and similar to those in the ESRD‐RH group. For all 3 groups, the maximum mean percent increase in procollagen type 1 N terminal propeptide and decrease in serum C‐telopeptide levels from baseline were observed on day 15. Changes in procollagen type 1 N terminal propeptide and serum C‐telopeptide were of similar patterns in all 3 groups. The single dose of romosozumab 210 mg was well tolerated. Adverse events (AEs) were reported for 13 patients (7 patients with severe RI and 6 with ESRD‐RH), with no deaths, AEs, or serious AEs leading to withdrawal. The incidence of subjects with postbaseline transient decreases in serum calcium (severe RI, n = 1; ESRD‐RH, n = 5) and increases in intact parathyroid hormone (severe RI, n = 7; ESRD‐RH, n = 7; healthy, n = 3) were greater in severe RI and ESRD‐RH groups than in the healthy group. All reported events of hypocalcemia (severe RI, n = 1; ESRD‐RH, n = 4) were asymptomatic. These results support the use of romosozumab without dose adjustment in patients with severe RI or ESRD‐RH.
ISSN:0091-2700
1552-4604
DOI:10.1002/jcph.2050