Randomized, Double-Blind Study of the Pharmacokinetics and Safety of Palivizumab Liquid Formulation Compared with Lyophilized Formulation

OBJECTIVE To assess the pharmacokinetics and safety of liquid palivizumab compared with lyophilized palivizumab. METHODS This phase 2, randomized, double-blind crossover study included premature infants aged ≤6 months born ≤35 weeks gestational age. Patients were randomized in a 1:1 ratio to receive a single 15 mg/kg intramuscular dose of liquid (sequence A group) or lyophilized (sequence B group) palivizumab on Day 0. Patients crossed over to receive the alternate formulation on Day 30. Serum palivizumab and antidrug antibody (ADA) levels were measured on Day 0 (predose), Day 30 (before the dose of alternate formulation), and Day 60 (30 days after the dose of alternate formulation). Patients were followed for safety through Day 60 (30 days after the dose of alternate formulation). RESULTS A total of 153 infants were randomized into the study (sequence A 75; sequence B 78). Sequence A and sequence B trough serum palivizumab levels were similar on Day 30 (51.7 and 49.1 µg/mL, respectively) and Day 60 (84.8 and 87.2 µg/mL, respectively). The ratio of the geometric means using both Day 30 and Day 60 serum concentrations was 1.040 (90% CI 0.998-1.083), which was within the prespecified bioequivalence range of 0.8-1.25. Adverse events (AEs) were similar between the palivizumab liquid and lyophilized groups and within each treatment sequence. Serious AEs (SAEs) were experienced by 3% of infants in both liquid palivizumab and lyophilized palivizumab groups. None of the SAEs were determined to be related to study drug. Among the 124 infants (81% of total) evaluated for ADA, 2 (1.6%) tested positive for ADA at Day 60 (1 in each of sequence A and B). CONCLUSION Liquid and lyophilized formulations of palivizumab were bioequivalent with similar safety profiles in infants.