Introduction
This study evaluated the bioequivalence of ezetimibe/rosuvastatin fixed dose combination compared to the concomitant administration of individual formulations (ezetimibe and ...rosuvastatin) in Chinese healthy subjects under fasting conditions.
Methods
This was a phase I, randomized, open-label, two-treatment, two-period, two-sequence, crossover study conducted in healthy Chinese participants under fasting conditions.
C
max
, AUC
0–
t
, and AUC
0–∞
from test and individual reference formulations were evaluated to assess bioequivalence. The safety assessments included adverse events (AEs)/treatment-emergent adverse events (TEAEs), potential clinically significant abnormalities (PCSAs) in vital signs, 12-lead electrocardiogram (12-ECG), and clinical laboratory parameters.
Results
Of the 68 subjects enrolled, 67 were treated. Systemic exposure to rosuvastatin based on
C
max
, AUC
0–
t
, and AUC
0–∞
was similar in both treatments, with respective arithmetic values 12.4 ng/ml, 117 ng·h/mL, and 120 ng·h/mL for test formulation and 12.7 ng/ml, 120 ng·h/mL, and 123 ng·h/mL for reference formulations. Similarly, systemic exposure to unconjugated ezetimibe was 4.14 ng/ml, 89.7 ng·h/mL, and 102 ng·h/mL for the test formulation and 3.80 ng/ml, 89.7 ng·h/mL, and 102 ng·h/mL for reference formulations. Systemic exposure to total ezetimibe was 70.5 ng/ml, 664 ng·h/mL, and 718 ng·h/mL for test formulation and 60.2 ng/ml, 648 ng·h/mL, and 702 ng·h/mL for reference formulations. The point estimates for rosuvastatin unconjugated ezetimibe and total ezetimibe were in the acceptable range of 0.80–1.25. No deaths or serious adverse events were reported.
Conclusions
Fixed dose combination of ezetimibe/rosuvastatin (10 mg/10 mg) achieved bioequivalence with reference to commercial tablets.
Trial Registration Number
CTR20202108.
Background and Objective
The combination of rosuvastatin and ezetimibe has promising clinical benefits with a significant safety and tolerability profile. However, there is a lack of clinical data ...supporting the drug–drug interaction (DDI) in Chinese population. Thus, the aim of this study is to assess the potential pharmacokinetic DDI between rosuvastatin and ezetimibe in a Chinese population.
Methods
In this randomized, open-label, phase 1 study, 12 healthy volunteers were randomized to three treatment groups: 10 mg rosuvastatin plus 10 mg ezetimibe, 10 mg rosuvastatin alone, and 10 mg ezetimibe alone under fasting conditions. The plasma concentrations of rosuvastatin and ezetimibe were determined, and the pharmacokinetic parameters were calculated. Primary endpoints were peak plasma concentration (
C
max
), area under the curve from zero to last measurement (AUC
0–t
), and area under the curve from zero to infinity (AUC
0–∞
) that were log-transformed, and co-administration was compared with monotherapy to evaluate the DDI.
Results
The geometric mean ratios (GMRs) of rosuvastatin with 90% confidence intervals (CIs) were 0.94 (0.80–1.12) for
C
max
, 0.96 (0.85–1.08) for AUC
0–t
, and 0.96 (0.86–1.07) for AUC
0–∞
when administered in combination with ezetimibe versus administered alone. The GMRs of unconjugated ezetimibe and total ezetimibe with 90% CIs were 1.15 (1.00–1.32) and 0.93 (0.80–1.07) for
C
max
, 0.96 (0.84–1.10) and 0.95 (0.83–1.08) for AUC
0–t
, and 1.06 (0.96–1.18) and 0.94 (0.80–1.11) for AUC
0–∞
, respectively, when administered in combination with rosuvastatin versus administered alone.
Conclusion
Co-administration of rosuvastatin and ezetimibe showed no clinically significant pharmacokinetic interactions in a healthy Chinese population.
Abstract
Context
Intravenous glucocorticoid (IVGC) is an accessible and affordable treatment for Graves orbitopathy (GO); the 4.5-g protocol is well studied, but many details of treatment protocols ...need to be clarified.
Objective
To compare the efficacy and safety of weekly and monthly protocol of IVGC in GO.
Methods
A prospective, randomized, observer-masked, single-center clinical trial, followed up to week 24, at the third affiliated hospital of Southern Medical University; 58 patients with active and moderate to severe GO, aged 18-60 years old, who had not received relevant treatment were included. The intervention was weekly protocol or monthly protocol of IVGC; both received a cumulative dose of methylprednisolone 4.5 g and had a duration of 12 weeks. The overall effective rate, improvement of quality of life (QOL) and signal intensity ratio (SIR) were measured.
Results
There was no significant difference in the effective rate between the 2 groups at week 12 and week 24 (86.21% vs 72.41%, P = .195; 86.21% vs 82.61%, P = .441), there was no significant difference in the improvement of clinical activity score, exophthalmos, soft tissue involvement, diplopia, and QOL. At week 24, the mean SIR and maximum SIR of the 2 groups were lower than those before treatment, and there were no statistically significant difference between the 2 groups. There was no significant difference in the incidence of adverse events between the 2 groups (31.03% vs 27.59%, P = .773).
Conclusion
The efficacy and safety of the 2 protocols are comparable; the monthly protocol could be used as an alternative to the weekly protocol.
