scholarly journals A Phase I, Randomized, Single-Dose Study to Evaluate the Biosimilarity of HOT-3010 to Adalimumab Among Healthy Chinese Male Subjects

2021 ◽  
Vol 12 ◽  
Author(s):  
Hong Zhang ◽  
Hong Chen ◽  
Xiaojiao Li ◽  
Min Wu ◽  
Xiaoxue Zhu ◽  
...  
Keyword(s):  
Reference Product ◽  
Parallel Study ◽  
Double Blind ◽  
Single Dose Study ◽  
Reference Drug ◽  
Treatment Groups ◽  
Dose Study ◽  
Healthy Chinese ◽  
Male Subjects ◽  
Chinese Male

Objective: This study explored the bioequivalence of a proposed biosimilar HOT-3010 vs. its reference product (adalimumab) among healthy Chinese male subjects. The study also investigated the tolerance, immunogenicity, and pharmacokinetics (PK).Methods: A randomized, double-blind, two-arm, parallel study was performed to examine the bioequivalence of HOT-3010 (40 mg) with that of adalimumab (Humira®, AbbVie) as a reference drug. The study subjects were followed up for 71 days.Results: PK properties exhibited by HOT-3010 (N = 66) and adalimumab (N = 68) groups were similar. The 90% confidence intervals of the ratios for Cmax, AUC0-t, and AUC0∞ were observed to be in the range 80–125% on comparing the two groups. For anti-drug antibodies (ADA), the number of subjects found to be positive in the HOT-3010 group and adalimumab group were 29 (43.94%) and 32 (47.06%), whereas 27 (40.91%) and 27 (39.71%) subjects were found to be positive for NAb, respectively. Treatment-related treatment-emergent adverse events (TEAEs) were recorded in 32 subjects each in both the groups, respectively.Conclusion: The PK characteristics and immunogenicity exhibited by HOT-3010 were similar to that of the reference product, adalimumab. The safety profiles were similar in both the treatment groups with mild-moderate adverse effects.

scholarly journals Pharmacokinetics, safety and tolerability of L-3-n-butylphthalide tablet after single and multiple oral administrations in healthy Chinese volunteers

2015 ◽  
Vol 51 (3) ◽  
pp. 525-531 ◽  
Author(s):  
Meng Wang ◽  
Quan-ying Zhang ◽  
Wen-yan Hua ◽  
Ming Huang ◽  
Wen-jia Zhou ◽  
...  
Keyword(s):  
Single Dose ◽  
Multiple Dose ◽  
Compartmental Analysis ◽  
Pharmacokinetic Parameters ◽  
Double Blind ◽  
Single Dose Study ◽  
Multiple Dose Study ◽  
Dose Study ◽  
Repeated Doses ◽  
Healthy Chinese

L-3-n-butylphthalide (L-NBP) is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40), or multiple doses of 160 mg twice daily for 7 days (n=12). Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses.

scholarly journals A Biosimilarity Study Between QX001S and Ustekinumab in Healthy Chinese Male Subjects

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Gao ◽  
Qingmei Li ◽  
Hong Zhang ◽  
Min Wu ◽  
Min Fang ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Geometric Mean ◽  
Area Under The Curve ◽  
Double Blind ◽  
Upper Respiratory Infection ◽  
Subject Variability ◽  
Healthy Chinese ◽  
Male Subjects ◽  
Chinese Male ◽  
Quantifiable Concentration

Objective: To evaluate the tolerance, variability, and pharmacokinetics (PK) of QX001S, a biosimilar for ustekinumab, in healthy Chinese men.Methods: One hundred and seventy-eight healthy men were recruited in this randomized, double-blind, single-dose, two-arm, parallel study, and received 45 mg of QX001S or ustekinumab in a single subcutaneous injection. PK, immunogenicity, and tolerance were evaluated in all participants for a period of 113°days.Results: The similarity between the two drugs was determined by comparing the baseline characteristics for each drug. The PK parameters were similar in the two groups: QX001S (n = 89) and ustekinumab (n = 88). The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) of QX001S to the reference (ustekinumab) for the maximum observable serum concentration (Cmax), area under the curve (AUC) from zero to the final quantifiable concentration (AUC0–t), and AUC from zero to infinity (AUC0–∞) were 100.90–118.68%, 98.71–115.26%, and 98.49–115.81%, respectively, which were within the predefined bioequivalence limit of 80.00–125.00%. High inter-subject variability (ranging from 32.0 to 33.5%) was observed. A total of 17 participants (19.1%) in the QX001S group and 36 (40.9%) in the ustekinumab group developed anti-drug antibodies (ADA) after administration. Nevertheless, the ADA did not affect the outcomes of the bioequivalence tests. Adverse reactions were recorded in 38 individuals injected with QX001S and 37 injected with ustekinumab. The most common adverse reactions were upper respiratory infection and elevated alanine aminotransferase.Conclusions: Our study ratified pharmacokinetic biosimilarity between QX001 S and ustekinumab, with high variability between subjects.

scholarly journals Pharmacokinetics, Immunogenicity and Safety Study for SHR-1309 Injection and Perjeta® in Healthy Chinese Male Volunteers

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingzi Cui ◽  
Dongyang Cui ◽  
Xinran Ren ◽  
Xuesong Chen ◽  
Guangwen Liu ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Geometric Mean ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Time Points ◽  
Healthy Chinese ◽  
Male Subjects ◽  
Chinese Male

Objectives: Pertuzumab is a monoclonal antibody for the treatment of breast cancer. The aim of this study was to compare the pharmacokinetics, immunogenicity and safety of the test preparation SHR-1309 injecta and the reference preparation Perjeta® in healthy Chinese male subjects.Methods: In this randomized, double-blind, single dose, two-way, parallel bioequivalence trial, a total of 80 qualified Chinese male subjects were selected and randomly divided into two groups. Each subject was intravenously injected with SHR-1309 or Perjeta®. Blood samples were collected at 21 different time points for pharmacokinetic analysis. In addition, immunogenicity was assessed at five different time points. The safety of the medication was monitored throughout the whole trial.Results: Cmax and AUC0-t were the primary pharmacokinetic parameters. Under a 90% confidence interval, their geometric mean ratios were 98.30 and 88.41% for SHR-1309 injection and Perjeta®, respectively. The geometric mean ratio of secondary pharmacokinetic parameters AUC0-∞ was 88.58%. These evaluation indexes are in the standard range of 80–125%, so SHR-1309 can be considered bioequivalent to Perjeta®. After 1,680 h (day 70) of administration, the two groups had 12 and 13 subjects who produced antidrug antibody (ADA), respectively. The occurrence time and proportion of ADA in SHR-1309 and Perjeta® were similar between subjects, and they had similar immunogenicity. During the entire trial period, there were 71 drug-related adverse reactions in 29 subjects who received SHR-1309 and 61 drug-related adverse reactions in 32 subjects who received Perjeta®. The incidence of adverse reactions between the two drugs was similar.Conclusion: The pharmacokinetic parameters, immunogenicity and safety of the biosimilar SHR-1309 injection produced by Shanghai Hengrui Pharmaceutical Co. Ltd. were similar to the original drug Perjeta® produced by Roche Pharma AG. The two drugs met the bioequivalence evaluation criteria. Therefore, SHR-1309 is bioequivalent to Perjeta®. Clinical trial registration: CTR20200,738.

scholarly journals A First-in-Human Safety, Tolerability, and Pharmacokinetics Study of Benapenem in Healthy Chinese Volunteers

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Cai-Yun Zhao ◽  
Yuan Lv ◽  
Yan Zhu ◽  
Min-Ji Wei ◽  
Meng-Ying Liu ◽  
...  
Keyword(s):  
Single Dose ◽  
Medical Intervention ◽  
Double Blind ◽  
Parent Molecule ◽  
Single Dose Study ◽  
Once Daily ◽  
Part C ◽  
Dose Study ◽  
Healthy Chinese ◽  
Multiple Intravenous Infusions

ABSTRACT The objective of this trial was to investigate the safety, tolerability, and pharmacokinetics (PK) of benapenem administered by single or multiple intravenous infusions in healthy Chinese volunteers. The trial was divided into 3 parts. In part A, 94 subjects were enrolled in a double-blind, placebo-controlled, sequential-ascending-single-dose study. The subjects were randomly assigned to groups receiving placebo or benapenem for injection at doses of 62.5, 125, 250, 500, 1,000, 2,000, or 3,000 mg. The effects of intravenous infusion time on the subjects of 250-, 500-, and 1,000-mg groups were explored. In part B, 12 subjects were enrolled in a single-dose PK study under fasting conditions and received 250, 500, or 1,000 mg of benapenem for injection. In part C, 36 subjects were given 250, 500, and 1,000 mg of benapenem for injection once daily for 7 consecutive days. The results showed that benapenem for injection was well tolerated during the studies. The major observed adverse events were mild, and all were resolved spontaneously without any medical intervention. Benapenem was mainly excreted through the kidneys in the form of parent molecule and metabolites. The PK and safety profiles of benapenem in healthy Chinese volunteers support its once-daily dosing in future clinical investigations. (Part A, part B, and part C have been registered at ClinicalTrials.gov under identifiers NCT03588156, NCT03578588, and NCT03570970, respectively.)

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