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Evogliptin (DA-1229) is a novel, potent, and selective dipeptidyl peptidase 4 (DPP-4) inhibitor for treating type 2 diabetes mellitus. This study investigates the effect of rifampicin on evogliptin pharmacokinetics. An open-label, crossover, one-sequence study was conducted on 12 healthy subjects. Reference baseline pharmacokinetic samples were collected on day 1 after the subjects were administered a single dose of 5 mg evogliptin. After a washout period, the subjects were administered 600 mg rifampicin once daily for 10 days, from days 8 to 17, for full induction of hepatic enzyme activity. On day 17, single doses of evogliptin (5 mg) were administered along with rifampicin (600 mg). The test pharmacokinetic samples were collected with a sampling schedule identical to that used for the reference. Maximum concentration (C ) and area under the plasma drug concentration-time curve (AUC ) of evogliptin with and without co-administration of rifampicin were compared. Reference and test C and AUC values of evogliptin were 4.70 ng/mL vs 4.86 ng/mL and 153.97 ng∙h/mL vs 58.83 ng∙h/mL, respectively. All adverse events were mild in intensity and considered unrelated to evogliptin administration. Rifampicin decreased the AUC of evogliptin by 61.8% without significantly affecting C . The mechanism underlying the decrease in AUC is thought to be the induction of cytochrome P450 (CYP), especially 3A, by rifampicin. The adverse events, none of which were serious, were not significantly altered by the concomitant administration of evogliptin and rifampicin. Nevertheless, it would be prudent that evogliptin dosing should be carefully considered when co-administered with CYP3A inducers.

Purpose: Filgrastim, a granulocyte-colony stimulating factor, is used to treat patients with neutropenia, including neutropenic fever. Leucostim[R] is a recombinant filgrastim product tested for biosimilarity with its reference product, Neupogen[R]. We conducted a comparative clinical trial of the 2 products. Patients and methods: A randomized, open-label, 2-way crossover, single-dose Phase I study was conducted for 56 healthy subjects. After a 5 and 10 [micro]g/kg single subcutaneous administration of test and reference product, pharmacokinetic and pharmacodynamic parameters (absolute neutrophil count and [CD34.sup.+] cell count) were compared. During the study, safety tests and adverse event monitoring were performed. Results: The test and the reference products had a comparable pharmacokinetic, pharmacodynamic, and safety profile. In both 5 and 10 [micro]g/kg dosing, the 90% CIs of the test to reference ratio for primary parameters (peak plasma concentration and area under the plasma concentration vs time curve from time 0 extrapolated to the infinite time for plasma filgrastim concentration; maximal effect and area under the time-effect curve from time 0 to time of the last quantifiable effect for absolute neutrophil count) were within the 0.8-1.25 range. In addition, safety profiles between the 2 products were similar without any serious adverse events. Conclusion: This study has provided firm clinical evidence that the test filgrastim product is similar to its reference filgrastim product. Keywords: bioequivalence, biosimilar, G-CSF, biologics

Filgrastim, a granulocyte-colony stimulating factor, is used to treat patients with neutropenia, including neutropenic fever. Leucostim is a recombinant filgrastim product tested for biosimilarity with its reference product, Neupogen . We conducted a comparative clinical trial of the 2 products. A randomized, open-label, 2-way crossover, single-dose Phase I study was conducted for 56 healthy subjects. After a 5 and 10 μg/kg single subcutaneous administration of test and reference product, pharmacokinetic and pharmacodynamic parameters (absolute neutrophil count and CD34 cell count) were compared. During the study, safety tests and adverse event monitoring were performed. The test and the reference products had a comparable pharmacokinetic, pharmacodynamic, and safety profile. In both 5 and 10 μg/kg dosing, the 90% CIs of the test to reference ratio for primary parameters (peak plasma concentration and area under the plasma concentration vs time curve from time 0 extrapolated to the infinite time for plasma filgrastim concentration; maximal effect and area under the time-effect curve from time 0 to time of the last quantifiable effect for absolute neutrophil count) were within the 0.8-1.25 range. In addition, safety profiles between the 2 products were similar without any serious adverse events. This study has provided firm clinical evidence that the test filgrastim product is similar to its reference filgrastim product.

CKD-519 is a selective and potent cholesteryl ester transfer protein (CETP) inhibitor being developed for the treatment of dyslipidemia to raise high-density lipoprotein cholesterol. We investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of CKD-519 in healthy adult subjects. A randomized, double-blinded, placebo-controlled, single ascending dose study was performed. Eight healthy subjects were enrolled in each CKD-519 dose group (25, 50, 100, 200, or 400 mg) and randomized to CKD-519 (n=6) or matching placebo (n=2). CKD-519 reached the maximum plasma concentration (C ) at 5-6 h post-dose, and had a long terminal half-life ranging between 40-70 h. The area under the plasma concentration-time curve (AUC) and C increased with the dose, however, C and AUC normalized by dose decreased with each incremental dose. CETP activity decreased with dose, and the maximum decrease (63%-83%) was observed at 6-8 h post-dose. A sigmoid E model best described the relationship between CKD-519 plasma concentrations and CETP activity with an EC of 17.3 ng/mL. Overall, 11 adverse events (AEs) were observed. All AEs were mild or moderate in intensity, and resolved without any complications. There were no clinically significant effects on blood pressure. In conclusion, single doses of CKD-519 up to 400 mg were well tolerated and showed potent inhibition of CETP activity.