Orally dispersible tablet (ODT) formulations of levo praziquantel (L‐PZQ) and racemic PZQ (rac‐PZQ) are being developed to treat schistosomiasis in preschool‐aged children. Two crossover studies (N = 32 and 36, respectively) assessed the relative bioavailability of these ODTs vs. Cysticide in adults. Bioavailability for L‐PZQ of ODT rac‐PZQ and Cysticide at 40 mg/kg was comparable (L‐PZQ area under the concentration‐time curve from zero to infinity (AUC 0–∞) test/reference ratio (90% confidence interval (CI)): 96% (84–111%)), whereas relative bioavailability of ODT L‐PZQ 20 mg/kg was ~40% that of Cysticide 40 mg/kg (test/reference: 40% (35–46%)). AUC 0‐∞ and peak plasma concentration (Cmax) were highly variable in both studies. For both ODTs, L‐PZQ AUC 0–∞ showed greater than dose‐proportional increase over the ranges tested and a significant food effect. Safety was comparable among formulations. The lower bioavailability of ODT L‐PZQ, as well as the high variability and nondose‐proportionality of pharmacokinetic (PK) parameters, highlighted the need for a dedicated pediatric dose‐finding study for the selection of the most appropriate formulation and dose (L‐PZQ ODT or rac‐PZQ ODT).

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Purpose: MSB11455 is a proposed biosimilar to the reference pegfilgrastim (Neulasta ®). This pivotal ANC (98.74e102.39), and area under the effectetime curve from time zero to time to last quantifiable concentration (97.30e100.23). Safety, tolerability, and immunogenicity were comparable between treatments. No filgrastim-specific neutralizing antibodies were detected with either treatment sequence. Implications: Pharmacokinetic and pharmacodynamic equivalence of MSB11455 and the reference product was shown, with comparable immunogenicity, safety, and tolerability between treatments. The study supports the biosimilarity of MSB11455 to the reference product. ClinicalTrials.gov identifier: NCT03251248.

e14514 Background: MSB11455 is a proposed biosimilar to the currently licensed pegfilgrastim (Neulasta). This phase I study (NCT03251248) assessed the pharmacokinetic (PK)/pharmacodynamic (PD) bioequivalence of MSB11455 to Neulasta. Methods: Healthy volunteers were randomized to one of two crossover sequences, MSB11455/Neulasta or Neulasta/MSB11455. Subjects received a single subcutaneous dose of either MSB11455 or Neulasta (both 6 mg/0.6 mL) on Day 1 of each study period. Samples for PK/PD analysis were taken predose and up to Day 16 postdose. Immunogenicity samples were taken predose and up to Day 84 postdose. Safety was assessed throughout the study. Results: 244 subjects were randomized and received both treatments. For all primary PK/PD parameters 90% repeated confidence intervals of the geometric mean ratio of MSB11455 versus Neulasta were within the pre-defined equivalence range (80.00%–125.00%): AUC0–∞ (96.59, 112.82), AUC0–last (97.29, 113.96), Cmax (97.13, 114.99), Emax (98.74, 102.39) and AUE0–t (97.30, 100.23). Safety and tolerability as well as immunogenicity were comparable between treatment sequences. No filgrastim-specific neutralizing antibodies were detected in either treatment sequence. Conclusions: PK/PD equivalence of MSB11455 and pegfilgrastim was demonstrated with comparable immunogenicity, safety, and tolerability. This study supports the biosimilarity of MSB11455 to Neulasta. Clinical trial information: NCT03251248.