A pharmacokinetic study of radiprodil oral suspension in healthy adults comparing conventional venous blood sampling with two microsampling techniques

Abstract

In this phase I, single-center, open-label study of ten heathy adults (18-45 years; NCT02647697), the PK, safety, and tolerability profile of radiprodil oral suspension in healthy adults were assessed, as well as two PK microsampling techniques. All participants received a single 30 mg radiprodil dose (12 mL oral suspension). Blood was collected at various time points using conventional venous sampling (intravenous catheter or venepuncture), and Mitra™ and Aqua-Cap™ Drummond microsampling (finger-prick and blood taken from venous blood sample tubes). Geometric mean radiprodil plasma concentrations from conventional venous samples were above the lower limit of quantification up to 48 hours after administration of a single oral dose of radiprodil. Geometric mean AUC inf and Cmax were 2042 h ng mL -1 and 89.4 ng mL -1, respectively. Geometric mean t½ was 15.8 hour; median tmax was 4 hour (range: 3-6 hour). Radiprodil exposure variables for Aqua-Cap™ Drummond sampling were similar to the conventional venous-derived data. Conversely, radiprodil exposure variables were lower with Mitra™ sampling compared with conventional venous sampling. The geometric mean ratio (90% confidence interval) for Cmax of conventional venous versus Mitra™ and Aqua-Cap™ Drummond sampling (finger-prick blood) was 0.89 (0.85, 0.94) and 1.03 (0.97,1.08), respectively, and therefore within the conventional bioequivalence range (0.80-1.25). Radiprodil oral suspension had an acceptable safety, tolerability, and palatability profile. The PK profile of radiprodil oral suspension was established in healthy adults, and was comparable when analyzed using conventional versus microsampling techniques. These results will support future radiprodil paediatric studies.

Keywords: bioequivalence; drug safety; pharmacokinetics; phase 1.

Figures

Figure 1

Microsampling techniques: (A) Mitra™ technique and (B) Aqua‐Cap™ Drummond technique

Figure 2

Geometric mean of radiprodil plasma concentration versus scheduled time following administration of radiprodil 30 mg oral suspension (PK‐PPS): comparison of Mitra™ and Aqua‐Cap™ Drummond microsampling techniques with conventional sampling on linear scale. Note: All sampling techniques were carried out on all participants (N =  10), at every time point described in the methods. This was with exception of Aqua‐Cap™ Drummond (venous) samples which were only calculated for three time points (2.5, 3 and 3.5 hours). PK‐PPS, pharmacokinetic per protocol set

Figure 3

Bland‐Altman plots for radiprodil concentrations (ng mL −1) measured from (A) Mitra™ peripheral and (B) Aqua‐Cap™ Drummond peripheral microsamples compared with conventional venous samples. The X axis shows the geometric mean of the radiprodil concentration measured by the two methods (peripheral microsampling and conventional venous). The Y axis shows the percentage difference between the radiprodil concentration measured by microsampling and conventional venous sampling (after back‐transformation of log data). Note: Accurate prediction with 10% homogeneous error. All sampling techniques were carried out on all patients (N = 10), at every time point described in the methods