Dataset Information

Comparison of the Pharmacokinetic-Pharmacodynamic Relationships of Two Darbepoetin Alfa Formulations in Healthy Male Volunteers.

ABSTRACT: OBJECTIVE:This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and safety properties of the test (CJ-40001) and reference (NESP®) versions of darbepoetin alfa following a single subcutaneous (SC) or intravenous (IV) administration in healthy male subjects. METHODS:A single-blind, randomized, single-dose, two-period, two-intervention crossover study was conducted, with two separate parts consisting of SC or IV administration. In each period, either a test or reference product was administered via the SC or IV route. Serial blood samples for PK analysis and the reticulocyte, hematocrit, hemoglobin, and red blood cell counts for PD analysis were collected for up to 360 or 264 h after SC or IV administration, respectively. The PK and PD parameters were calculated using non-compartmental methods. The 90% confidence intervals of the geometric mean ratios for the PK and PD parameters between the two interventions were estimated. Safety and anti-drug antibody profile assessments were performed. RESULTS:The mean darbepoetin alfa concentration-time profiles were comparable between the two products for SC and IV administration. Additionally, the PD and safety profiles were similar between the two products. Anti-drug antibody reactivity was negative for all samples from both intervention groups for SC and IV administration. The time-matched serum darbepoetin alfa concentration and the PD markers presented a counter-clockwise hysteresis, which suggests a time delay between the exposure and response. CONCLUSION:The test and reference darbepoetin alfa formulations had similar PK, PD, and safety profiles. Thus, it is expected that the two formulations are able to be used interchangeably in clinical settings. ClinicalTrials.gov Identifier: NCT03542916.

SUBMITTER: Kim S

PROVIDER: S-EPMC6373390 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Comparison of the Pharmacokinetic-Pharmacodynamic Relationships of Two Darbepoetin Alfa Formulations in Healthy Male Volunteers.

Kim Seokuee S Hong Taegon T Ko Jae-Wook JW Huh Wooseong W Kim Jung-Ryul JR

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 20190201 1

<h4>Objective</h4>This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and safety properties of the test (CJ-40001) and reference (NESP<sup>®</sup>) versions of darbepoetin alfa following a single subcutaneous (SC) or intravenous (IV) administration in healthy male subjects.<h4>Methods</h4>A single-blind, randomized, single-dose, two-period, two-intervention crossover study was conducted, with two separate parts consisting of SC or IV administration. In each period, either a test ...[more]

PMID: 30506495

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Project description:Background and objectiveA novel tiotropium bromide monodose capsule dry powder inhaler (DPI) formulation and device have been developed. The formulation was based on a spray-dried matrix that enhances the aerosolizaton properties, allowing a less active tiotropium metered dose (13 µg/capsule) while maintaining the same delivered dose (10 µg/actuation). This study describes the pharmacokinetic bioequivalence to the reference product.MethodsThis randomized, two-stage, crossover, semi-replicate (three-way) study was performed in healthy volunteers. In each study period, subjects received a single dose of two capsules (20 μg delivered dose) of the study medication, separated by a 14-day washout period: tiotropium 10 μg delivered dose (Laboratorios Liconsa, Spain) and Spiriva HandiHaler(®) (Boehringer Ingelheim Pharma GmbH & Co KG, Germany). Blood samples were obtained up to 48 h post-dose to evaluate the comparative bioavailability. Tiotropium was measured in plasma by means of dual stage liquid-liquid extraction followed by the two-dimensional ultra-high performance liquid chromatography sensitive sub-pg/mL bioanalytical method. The main pharmacokinetic parameters were maximum plasma concentration (C max), area under the concentration-time curve (AUC) from time zero hours to the last observed concentration at time t (AUC t ), and AUC from time zero hours to 30 min (AUC0.5). Bioequivalence was accepted if the 90.20 % confidence interval (CI) for the ratio test/reference of the primary pharmacokinetic parameters lay within the acceptance range of 80-125 %. Safety assessment was a secondary endpoint.ResultsA total of 30 subjects were randomized and bioequivalence was demonstrated for all primary pharmacokinetic parameters: C max (CI 87.26-106.60 %), AUC t (CI 101.33-111.64 %), and AUC0.5 (CI 97.95-113.49 %). Both study treatments were well tolerated (four non-serious adverse events [AEs] were reported in four subjects: one AE before any product administration, two AEs after test product administration; and one AE after reference product administration).ConclusionsBoth products containing tiotropium 10 µg delivered-dose DPI were bioequivalent and showed good tolerability and a similar safety profile.

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Dataset Information

Comparison of the Pharmacokinetic-Pharmacodynamic Relationships of Two Darbepoetin Alfa Formulations in Healthy Male Volunteers.

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Comparison of the Pharmacokinetic-Pharmacodynamic Relationships of Two Darbepoetin Alfa Formulations in Healthy Male Volunteers.

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