Pharmacokinetic Characteristics, Safety, Tolerability and Immunogenicity of LY01008 and Avastin in Healthy Chinese Male Subjects
Ontology highlight
ABSTRACT:
DISEASE(S): Non Small Cell Lung Cancer Recurrent,Metastatic Colorectal Cancer,Carcinoma, Non-small-cell Lung,Lung Neoplasms,Non Small Cell Lung Cancer Metastatic
PROVIDER: 2394704 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:IntroductionTelaprevir, a reversible selective inhibitor of viral protease and a potential blocker of viral replication, is indicated for the treatment of hepatitis C virus genotype 1 infection. In this study, the pharmacokinetic profile, safety, and tolerability of telaprevir and the effect of food on telaprevir exposure were evaluated in healthy Korean subjects, and compared with data from a previous study in Japanese male subjects.MethodsThe single ascending dose study was conducted in 3 dose-based groups (500, 750, and 1,250 mg, six subjects each) in a fasted state. In the multiple dose study, eight subjects in the fed state received 750 mg of telaprevir once on Day 1 and every 8 hours from Day 2 until the morning of Day 6. Serial blood samples for pharmacokinetic analysis were collected for up to 24 hours in the single ascending dose study and for 6 days in the multiple dose study. Individual pharmacokinetic parameters were calculated using a non-compartmental analysis method. Safety and tolerability profiles were evaluated throughout the study.ResultsFollowing multiple administrations of telaprevir, maximum plasma concentrations (Cmax), area under the concentration-time curve (AUC0-8), and Ctrough (concentration at 8 h after drug administration) increased by ~2.41-fold. Compared to fasted state values, mean Cmax and AUC0-24 increased by 4.92- and 4.81-fold, respectively, after food intake. The Cmax and AUCinf of Korean subjects were 26%-34% higher than those of Japanese subjects; however, these differences were not clinically significant. All observed adverse events were mild and there was no discontinuation due to AEs.ConclusionIn conclusion, the telaprevir's pharmacokinetic characteristics were similar in Korean and Japanese subjects. Telaprevir was well tolerated in a single dose of up to 1,250 mg and in multiple doses of 750 mg.
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Project description:Introduction:Major cardiovascular risk factors, including hypertension and dyslipidemia, are often comorbidities, frequently leading to concurrent prescription of angiotensin receptor blockers and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). The study's objective was to evaluate the effect of coadministration of fimasartan and atorvastatin on their pharmacokinetics (PKs). Subjects and methods:In a randomized, open-label, three-period, six-sequence, crossover, multiple-dose study, 36 healthy subjects received 120 mg fimasartan, 40 mg atorvastatin, or both (based on their assigned sequence) once daily for 7 days in each period, with a 7-day washout between periods. Blood samples for the PK analysis of fimasartan, atorvastatin, and the 2-hydroxy atorvastatin metabolite were collected up to 48 h after the last dose. Results:The coadministration of fimasartan and atorvastatin was well tolerated and led to an increase in the peak concentration and area under the concentration-time curve at steady state of fimasartan by 2.18-fold (95% confidence interval [CI], 1.79-2.65) and 1.35-fold (95% CI, 1.26-1.43) and those of atorvastatin increased by 1.82-fold (95% CI, 1.51-2.18) and 1.12-fold (95% CI, 1.04-1.22), respectively. Conclusion:Coadministration increased the systemic exposures of fimasartan and atorvastatin, but the clinical significance of this finding needs to be evaluated with respect to exposure responses and clinical outcomes.
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2013-01-02 | E-GEOD-33654 | biostudies-arrayexpress
Project description:Purpose: Evogliptin, a dipeptidyl peptidase-4 inhibitor, and glimepiride, a sulfonylurea, are used to treat type 2 diabetes mellitus. In this study, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between evogliptin and glimepiride.Materials and methods: A randomized, open-label, 3-period, 3-treatment, 2-sequence crossover study was conducted in healthy male subjects. During each period, subjects received multiple doses of evogliptin 5 mg alone (EVO), glimepiride 4 mg alone (GLI), or a combination of the two (EVO+GLI). Serial blood and urine samples were collected 168 and 24 h post dosing, respectively, for PK and PD analyses.Results: Thirty-four subjects completed the study. The co-administration of evogliptin and glimepiride did not alter their plasma and urine PK profiles. For evogliptin, the geometric mean ratio (GMR) (90% confidence intervals) for the maximum plasma concentrations at steady-state (Cmax,ss) and the area under the curve during dosing interval at steady-state (AUC?,ss) of EVO+GLI to E were 1.02 (0.98-1.06) and 0.97 (0.95-1.00), respectively. For glimepiride, the corresponding values of EVO+GLI to GLI were 1.08 (1.01-1.17) and 1.08 (1.02-1.14), respectively. All values were within the regulatory bioequivalence criteria of 0.8-1.25. Glucose excursion decreased with the co-administration of evogliptin and glimepiride compared with that observed with the evogliptin or glimepiride monotherapy.Conclusion: Evogliptin and glimepiride had no PK interactions when co-administered, while the combination therapy showed an additive glucose-lowering effect compared to those of evogliptin or glimepiride monotherapy.
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Project description:AimEvogliptin is a newly developed oral glucose-lowering medication of the dipeptidyl peptidase 4 (DPP-4) inhibitor class for type 2 diabetes mellitus. The combination of a DPP-4 inhibitor with pioglitazone is a promising therapeutic option. The aim of the present study was to evaluate the pharmacokinetic and pharmacodynamic interaction between evogliptin and pioglitazone.Materials and methodsA randomized, open-label, multiple-dose, three-treatment, three-period, six-sequence crossover study was conducted in healthy Korean male subjects. All subjects received evogliptin 5 mg once daily for 7 days (EVO), pioglitazone 30 mg once daily for 7 days (PIO) and co-administration of evogliptin 5 mg and pioglitazone 30 mg once daily for 7 days (EVO+PIO) according to the assigned sequence and period. Serial blood samples were collected for 24 hours for pharmacokinetic analysis and 3 hours after the oral glucose tolerance test for the pharmacodynamic analysis.ResultsThirty-four subjects completed the study. EVO+PIO and EVO showed a similar maximum plasma concentration at steady state (Cmax,ss) and area under the concentration-time curve during the dosing interval at the steady state (AUCτ,ss) of evogliptin, with geometric mean ratios (GMRs) (90% confidence interval (CI)) of 1.01 (0.97-1.05) and 1.01 (0.98-1.04), respectively. EVO+PIO and PIO showed a similar Cmax,ss and AUCτ,ss of pioglitazone, with GMRs (90% CI) of 1.07 (0.99-1.17) and 1.08 (0.99-1.17), respectively. Reduction of the glucose level after EVO+PIO was larger compared to PIO and similar with EVO.ConclusionConcomitant administration of evogliptin and pioglitazone showed similar glucose-lowering effects with those of evogliptin alone without pharmacokinetic interactions when compared to the intake of each drug alone.
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2007-07-14 | E-CBIL-32 | biostudies-arrayexpress
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2024-11-28 | PXD055124 | Pride