ABSTRACT
This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar HEC14028 compared to reference Trulicity® (dulaglutide) in healthy male Chinese subjects. This study was a single-center, randomized, open, single-dose, parallel-controlled comparative Phase I clinical trial, including a screening period of up to 14 days, a 17-day observation period after administration, and a 7-day safety follow-up period. A total of 68 healthy male subjects were randomly assigned (1:1) to the test group (HEC14028) and the reference group (dulaglutide) (single 0.75 mg abdominal subcutaneous dose). The primary objective was to evaluate the pharmacokinetic characteristics of HEC14028 and compare the pharmacokinetic similarities between HEC14028 and dulaglutide. The primary PK endpoints were maximum plasma concentration (Cmax) and area under the blood concentration-time curve from zero time to the estimated infinite time (AUC0-∞). The study results showed that HEC14028 and dulaglutide were pharmacokinetically equivalent: 90% confidence interval (CI) of Cmax and AUC0-∞ geometric mean ratios were 102.9%-122.0% and 97.1%-116.9%, respectively, which were both within the range of 80.00%-125.00%. No grade 3 or above treatment emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to withdrawal from the trial, or TEAEs leading to death were reported in this study. Both HEC14028 and dulaglutide showed good and similar safety profiles, and no incremental immunogenicity was observed in subjects receiving HEC14028 and dulaglutide.
Subject(s)
Biosimilar Pharmaceuticals , Glucagon-Like Peptides , Glucagon-Like Peptides/analogs & derivatives , Healthy Volunteers , Immunoglobulin Fc Fragments , Recombinant Fusion Proteins , Humans , Male , Immunoglobulin Fc Fragments/administration & dosage , Immunoglobulin Fc Fragments/adverse effects , Immunoglobulin Fc Fragments/immunology , Glucagon-Like Peptides/pharmacokinetics , Glucagon-Like Peptides/administration & dosage , Glucagon-Like Peptides/adverse effects , Recombinant Fusion Proteins/pharmacokinetics , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Biosimilar Pharmaceuticals/pharmacokinetics , Biosimilar Pharmaceuticals/administration & dosage , Biosimilar Pharmaceuticals/adverse effects , Adult , Young Adult , China , Area Under Curve , Asian People , Therapeutic Equivalency , Injections, Subcutaneous , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Middle Aged , Adolescent , East Asian PeopleABSTRACT
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 (Cmax), area under the curve from zero to last measurement (AUC0-t), and area under the curve from zero to infinity (AUC0-∞) 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 Cmax, 0.96 (0.85-1.08) for AUC0-t, and 0.96 (0.86-1.07) for AUC0-∞ 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 Cmax, 0.96 (0.84-1.10) and 0.95 (0.83-1.08) for AUC0-t, and 1.06 (0.96-1.18) and 0.94 (0.80-1.11) for AUC0-∞, 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.
