The Safety, Toleration, and Pharmacokinetics of Two Intravenous Voriconazole Formulations in Healthy Chinese Volunteers After Increasing Dose Administrations.

Sulfobutyl ether-beta-cyclodextrin sodium salt contained in the marketed intravenous voriconazole injection as a solubilizer may cause harmful accumulations. This study aimed to evaluate the safety, tolerability, and pharmacokinetics (PKs) of two intravenous voriconazole formulations containing excipients from different manufacturers using increasing dose administrations in healthy Chinese volunteers. A randomized, double-blind, placebo-controlled trial was conducted in three cohorts with 42 healthy Chinese volunteers. Each cohort of 14 volunteers was allocated in proportion (8:4:2) to test the formulation, reference voriconazole, or placebo successively by single-dose then multiple-dose administrations of 3, 4, and 6 mg/kg. Forty-one volunteers completed all drug administrations. The pharmacokinetics of test formulations are characterized by high interindividual variability (coefficient of variance of Cmax up to 68.0%, AUC0-τ up to 70.2%, and nonlinear PKs with a regression coefficient of Cmax  = 1.31 and AUC0-τ  = 1.75 in a single dose). In the steady state, RAuc of the test drug versus reference drug of the 3, 4, and 6 mg/kg dose group were 5.2 and 5.3, 5.6 and 6.3, and 5.8 and 5.5, respectively, and Rcmax were 2.5 and 2.7, 2.6 and 3.1, and 2.8 and 2.6, respectively. Eighty-three adverse events with 37 transient visual disturbances were mild. PKs with high interindividual variability, nonlinear characteristics, and significant dose-dependent accumulation were comparable between the two formulations. Overall, the safety of the test formulation was acceptable.

Application of a Cloud Video Conference Method for Recruiting Healthy Subjects Into an Early-Phase Clinical Trial During the COVID-19 Pandemic.

Objective: Our objective is to explore the effect of applying cloud video conferencing methods to the informed consent process in an early-phase clinical trial during the COVID-19 pandemic. Methods: All participants who intended to participate in the trial were informed via a cloud video conference before signing the informed consent forms (ICF). Then, the attitudes of the participants with the cloud video conference and their understanding of the trial were evaluated using a questionnaire when they visited to sign the ICF onsite. Results: A total of 165 subjects participated in the cloud video conference process, and 142 visited the site to sign and date the ICFs at the center during the appointment time. The survey showed that nearly 100% of the subjects evaluated the video-based informed consent process as very good or good and gave correct answers to questions about the trial. Furthermore, 136 (95.8%) subjects believed that the knowledge about the trial derived via the video-based informed consent process was consistent with the onsite reality, and 139 (97.9%) subjects expressed their willingness to participate in an informed consent procedure undertaken through an online video conference. Conclusions: The video-based informed consent process achieved the same effects as an onsite informed consent process. The former saves time and cost of transportation for the subject and exhibits good public acceptance; especially in light of the COVID-19 pandemic, this process is conducive for reducing the risk of subject infection due to travel and would also help avoid crowding on site.

The motivations, barriers, and sociodemographic characteristics of healthy Chinese volunteers in phase I research.

PURPOSE: To describe the motivations, barriers, and sociodemographic characteristics of healthy Chinese volunteers in phase I research and to demonstrate the factors influencing their willingness to participate in subsequent trials. METHODS: Healthy subjects who participated in seven phase I trials at two centres were invited to participate in the cross-sectional survey at discharge by anonymously and voluntarily completing the self-administered questionnaire. RESULTS: From 442 subjects asked to complete the questionnaire, a response rate of 94.8% (419) was obtained, and 72.8% of the respondents had participated in a mean of 2.0 ± 1.3 previous studies. Over 90% of the subjects indicated that the main motivations to participate trials were to help more people, to contribute to scientific research, and to obtain money. The top 5 barriers were time inconvenience, advertisement sources, potential risks associated with the drug, privacy, and the route of drug administration. Nearly half (49.6%) of the subjects were willing to participate in the next trial. The factors impacting the willingness of the subjects to participate in subsequent trials were gender, screening frequency, enrolment frequency, level of understanding of the research, two motivating factors (to make money and receive a free check-up), and ten barriers (e.g. risk, distance, living conditions, and trust). CONCLUSIONS: The majority of healthy Chinese subjects were young, were less well educated, had low income levels, and had poor medical insurance coverage. Given the multiple sources of motivation and complex barriers to trial participation, investigators and recruitment staff should consider ethics aspects to guarantee volunteer safety and well-being.

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study.

OBJECTIVES: To evaluate the pharmacokinetic properties and safety of empagliflozin, and the bioequivalence of test formulation empagliflozin tablet compared with the brand-name drug Jardiance (reference formulation) after single oral administration under fasting and fed conditions in healthy Chinese subjects. METHODS: An open-label randomized single-dose two-sequence, two-treatment, two-period crossover study was conducted in healthy Chinese subjects, with 30 subjects under fasting condition and another 30 subjects under fed condition. Under each condition, subjects received a single oral administration of either the test or reference empagliflozin formulation, and then they received a single oral dose of the other formulation after a 7-day washout period. RESULTS: A total of 29 subjects under each condition completed the study. The maximum plasma drug concentration, the area under the plasma concentration-time curve (AUC) from 0 to t (AUC0-t ), and the AUC from 0 to infinity (AUC0-∞ ) of test formulation and reference formulation was 186.90 ± 47.21 and 190.60 ± 40.94 ng/ml, 1303.04 ± 234.28 and 1267.78 ± 217.07 ng·hour/ml, and 1328.08 ± 243.84 and 1293.22 ± 224.82 ng·hour/ml under fasting condition, and 151.55 ± 23.86 and 154.08 ± 30.40 ng/ml, 1215.65 ± 197.62 and 1199.26 ± 186.23 ng·hour/ml, and 1241.76 ± 202.47 and 1225.54 ± 192.10 ng·hour/ml under fed condition, respectively. CONCLUSIONS: The two formulations of empagliflozin were bioequivalent, and both were generally well tolerated under fasting and fed conditions.

A Phase I, Randomized, Single-Dose Study Evaluating the Biosimilarity of TAB008 to Bevacizumab in Healthy Volunteers.

Objective: This study compared the pharmacokinetics (PK), safety, and immunogenicity of the biosimilar TAB008 monoclonal antibody to bevacizumab (Avastin®) in normal healthy Chinese male volunteers. Methods: In this randomized, double-blind, parallel controlled study, a total of 100 healthy Chinese male subjects were randomized (1:1) to receive a single 1 mg/kg intravenous dose of TAB008 or Avastin® over a 90-min infusion. The subjects were followed for 99 days after drug administration. Primary endpoints were bioequivalence of major pharmacokinetic parameters (AUC0-t and AUC0-∞) and maximum observed serum concentration (Cmax). Secondary endpoints included safety and immunogenicity parameters. Results: The two groups of test subjects (49 subjects in the TAB008 group and 50 subjects in the Avastin® group) were well matched in regards to all demographic and baseline characteristics. The treatment group ratios of LS geometric means for the three primary PK parameters were fully contained within the bioequivalence limits of 80.00-125.00% (90% CI was 103.66-118.33% for Cmax, 94.32-111.72% for AUC0-t, and 94.69-112.23% for AUC0-∞). Treatment-emergent adverse events (TEAEs) were reported for 24 (49.0%) subjects in the TAB008 group and 22 (44.0%) subjects in the Avastin® group. TEAEs related to the study drug were reported for 19 (38.8%) subjects in the TAB008 group and 19 (38.0%) subjects in the Avastin® group. National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 3 TEAEs were reported for 1 (2.0%) subject in the TAB008 group and 3 (6.0%) subjects in the Avastin® group. There were no Grade 4 or 5 TEAEs or serious adverse events (SAEs) during the study. Anti-drug antibody generation was reported once only in each group, and neutralizing antibody (Nab) analysis was negative upon follow-up. Conclusion: TAB008 attained pharmacokinetic similarity to bevacizumab, and was safe and well tolerated.

Bioequivalence study of single-dose lenalidomide capsule vs. Revlimid® capsule in healthy Chinese males.

OBJECTIVE: Lenalidomide is a 4-amino-glutaryl derivative of thalidomide and belongs to a new generation of immunomodulatory agents for the treatment of patients with myelodysplastic syndrome and multiple myeloma. The aim of this study is to evaluate the bioequivalence and safety of a capsule containing 25 mg of a test formulation of lenalidomide and a 25 mg Revlimid® capsule in healthy, Chinese adult males for good quality anti-cancer medicine with lower costs. METHODS: This was a single-center, randomized, open-label, single-dose, two-period, crossover pharmacokinetic study. Forty-eight healthy, adult Chinese males were administered a test lenalidomide or Revlimid® capsule, 24 in a fasted and 24 in a fed state, followed by crossover to the other capsule. RESULTS: Twenty-four subjects in the fasting group and 23 in the postprandial group completed the clinical trial. Subjects administered test lenalidomide and Revlimid® capsules in the fasting state had a Cmax of 564 ± 153 and 609 ± 121 ng/mL, respectively; an AUC0-t of 1660 ± 211 and 1660 ± 235 h ng/mL, respectively; and an AUC0-∞ of 1670 ± 210 and 1670 ± 237 h ng/mL, respectively. In the fed state, the subjects had a Cmax of 389 ± 105 and 383 ± 101 ng/mL, respectively; an AUC0-t of 1770 ± 314 and 1740 ± 360 h ng/mL, respectively; and an AUC0-∞ of 1800 ± 316 and 1760 ± 362 h ng/mL, respectively. Both capsules were well tolerated, with no serious adverse events observed. CONCLUSION: According to the criteria for bioequivalence, the test formulation of lenalidomide and Revlimid® was determined to be bioequivalent.