A randomized, double-blind, single-dose, parallel two-group study comparing the pharmacokinetics, safety, and immunogenicity of BAT1806 SC with tocilizumab in healthy Chinese male subjects

Secukinumab, a monoclonal antibody targeting interleukin (IL)-17A, is approved for the treatment of psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, enthesitis-related arthritis, and hidradenitis suppurativa. This study compared the pharmacokinetics (PK), safety, and immunogenicity of CMAB015, a candidate secukinumab biosimilar, with the reference product secukinumab (Cosentyx®) in healthy Chinese male subjects. This double-blind, parallel-group study randomized healthy Chinese male subjects (N=130) to receive either a single dose of 150 mg CMAB015 or secukinumab subcutaneously. Primary study endpoints were PK parameters such as the maximum concentration (Cmax) and area under the curve from zero to infinity (AUC0-inf), while safety and immunogenicity were secondary endpoints. The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of Cmax and AUC0-inf for CMAB015 to secukinumab were all within the bioequivalence limits (80.00-125.00%). Other PK parameters were comparable between the groups. The safety profile of CMAB015 was similar to that of secukinumab, with no serious adverse events related to treatment. The incidence of TEAEs was slightly higher in the CMAB015 group, but these events were mild to moderate in severity and did not lead to any withdrawals from the study. Immunogenicity analysis revealed low rates of anti-drug antibody (ADA) positivity, with similar rates between CMAB015 and secukinumab. This study demonstrated equivalent PK, comparable safety, and immunogenicity of CMAB015 to secukinumab in healthy Chinese male subjects. These findings support further clinical evaluation of CMAB015 as a secukinumab biosimilar. The trial was registered on Clinicaltrials.gov (Identifier No. NCT05734482) and Chinadrugtrials.org.cn (Identifier No. CTR20230105).

This study aimed to compare the pharmacokinetic (PK) profiles, safety, and immunogenicity of the proposed A140 with those of cetuximab (Erbitux®) in healthy Chinese male subjects. We conducted a randomized, single-dose, double-blind, parallel-controlled phaseI study in which 82healthy subjects were randomized equally into the A140 group and the cetuximab group. Both the test and comparator drug were administered as a single intravenous (IV) dose of 250mg/m2. Blood samples were collected as per a designated schedule to evaluate PKs and immunogenicity. Safety was assessed throughout the study. PK similarity was concluded if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of the A140 to cetuximab for area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) were within the predefined bioequivalence range of 80-125%. The results showed that the 90%CI of the GMR for PK parameters (AUC0-t, AUC0-∞, Cmax) between the A140 and cetuximab groups were all within the predefined equivalent interval of 80-125%. Furthermore, the types of treatment-related adverse events were similar between the two groups, with an incidence of 100%. However, approximately 80% of these events belonged to Common Terminology Criteria for Adverse Events (CTCAE) grade1 or 2. Anti-drug antibody (ADA) profiles were comparable between the A140 and the cetuximab group. A140 demonstrated similar PK to cetuximab and comparable safety and immunogenicity in healthy Chinese male subjects. CTR20182229 ( https://www.chinadrugtrials.org.cn/ ).

Background Dulaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been approved for improving glycemic control and reducing the risk of cardiovascular (CV) adverse events. This study compared the pharmacokinetic (PK) profiles, safety, and immunogenicity of LY05008, a biosimilar candidate, to a licensed product dulaglutide in healthy Chinese male subjects. Research design and methods In this double-blind, open-label, parallel-group study, healthy Chinese male subjects were randomized 1:1 to receive either LY05008 or dulaglutide subcutaneously. Primary study endpoints were PK parameters such as the area under the concentration-time curve (AUC) from time zero to infinity (AUC0 – ∞), AUC from time zero to the last quantifiable concentration (AUC0–t), and maximum serum concentration (Cmax). Safety and immunogenicity profiles were also included for data analysis. Results 82 subjects were randomized to receive LY05008 (n = 41) or dulaglutide (n = 41). The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUC0 – ∞, AUC0–t and Cmax of LY05008 to dulaglutide were all within the bioequivalence limits of 80%-125%. Other PK parameters, safety, and immunogenicity profiles were comparable across the two treatment groups. Conclusion This study demonstrated PK similarity of LY05008, a dulaglutide biosimilar, to dulaglutide in healthy Chinese male subjects, with comparable safety and immunogenicity data. Trial registration The trial is registered at the Chinese Clinical Trial Registry (Identifier No. ChiCTR2200066519).

Effects of Food on the Pharmacokinetic Properties of Surufatinib: A Phase I, Single-dose, Randomized, Open-label Crossover Study in Healthy Subjects

Background Bevacizumab, an inhibitor of angiogenesis, has been approved in several anti-cancer therapies. This study compared the pharmacokinetic (PK) profiles, safety, and immunogenicity of a bevacizumab biosimilar, LY01008, with those of European Union – approved bevacizumab (Avastin®) in healthy Chinese males. Research Design and Methods In this double-blind, open-label, parallel-group study, healthy Chinese male subjects were randomized 1:1 to receive either LY01008 or Avastin® 3 mg/kg intravenously. Primary study endpoints were PK parameters such as the area under the concentration-time curve (AUC) from time zero to infinity (AUC0–∞), AUC from time zero to last quantifiable concentration (AUC0–t), and maximum serum concentration (Cmax). Secondary study endpoints included safety, tolerability, and immunogenicity. Results One hundred and twelve subjects were randomized to receive LY01008 (n = 56) or Avastin® (n = 56). The 90% CIs of the GMRs of AUC0–t, AUC0–∞, and Cmax of LY01008 to Avastin® were all within the bioequivalence margin. Other PK parameters, safety, and immunogenicity profiles were comparable across the two treatment groups. Conclusions This study demonstrated equivalent PK, comparable safety, and similar immunogenicity of LY01008 to Avastin® in healthy subjects, thus paving the way for further clinical evaluation. Trial Registration The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05110118).

This study aimed to compare the pharmacokinetics, safety, and immunogenicity of the prefilled syringe (PFS) with lyophilized (LYO) recombinant human tumor necrosis factor-α receptor II:lgG Fc fusion protein (rhTNFR:Fc) in healthy Chinese male subjects. A single-center, randomized, open-label,2-period, crossover study was performed in healthy Chinese male subjects. Subjects were randomly assigned into 2 sequences and received a subcutaneous injection of 25 mg rhTNFR:Fc PFS or rhTNFR:Fc LYO (Anbainuo), with a 35-day washout between the 2 periods. Blood samples were collected at specified time intervals, and then serum concentrations of rhTNFR:Fc were analyzed by enzyme-linked immunosorbent assay. The maximum serum concentration, area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity were all calculated and evaluated. Meanwhile, safety and immunogenicity were also assessed. A total of 82 subjects completed the study, and six subjects withdrew for various reasons. The 90%CIs for geometric mean ratios of maximum serum concentration, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity were all within the equivalence range of80% to 125%. Safety was comparable between the 2 formulations with low immunogenicity. rhTNFR:Fc PFS exhibited similar pharmacokinetic and safety profiles of rhTNFR:Fc LYO (Anbainuo) in healthy Chinese male subjects.

Background: To compare the pharmacokinetic (PK) profile, safety, and immunogenicity between golimumab and the biosimilar BAT2506 in healthy Chinese male subjects. Research design and methods: A total of 180 healthy male subjects were recruited for this randomized, double-blinded, single-dose, parallel study. They received 50 mg BAT2506 or golimumab (1:1 ratio) by single subcutaneous injection. The evaluation index included maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC0-t, AUC0-∞), safety, and immunogenicity. Results: The results showed that the 90% confidence interval (CI) of the geometric mean ratio (GMR) of BAT2506 to reference drug (golimumab) for Cmax, AUC0–∞ and AUC0-t were 99.26% (90.59–108.76%), 102.06% (93.31%–111.64%), and 102.05% (93.51–111.38%), respectively. All 90% CIs were within the range of 80–125% range, which is the limitation of the equivalence margin. Furthermore, similarity of treatment-emergent adverse events was also found between the two drugs. A total of 14 subjects (7.8%) developed anti-drug antibody after administration. Conclusions: Our study confirmed the PK similarity between BAT2506 and golimumab, and showed good tolerance of BAT2506 in healthy subjects. There were no differences in safety and immunogenicity between the two drugs. Therefore, BAT2506 meets the criteria for biosimilarity to golimumab. Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04152759).

New intravenous and solid oral formulations of the antifungal agent posaconazole have been developed. This randomized, open-label, crossover study in 18 healthy adult Chinese male and female subjects evaluated the pharmacokinetics of single-dose posaconazole (oral 300-mg posaconazole tablet fasted, intravenous 300-mg posaconazole solution fasted, and oral 300-mg posaconazole tablet with standard high-fat breakfast). Primary objectives were to determine the single-dose pharmacokinetics of posaconazole in healthy Chinese subjects when administered as an intravenous solution and as an oral tablet under fasted conditions and the effect of food on the absorption of posaconazole. The three treatments consisted of the following: a single oral dose of posaconazole 300mg (fasted), a single oral dose of posaconazole 300mg (high-fat breakfast), and a single intravenous dose of posaconazole 300mg (fasted). Blood samples for pharmacokinetic analysis were collected before dosing and at regular intervals after dosing. Adverse events were monitored throughout. The pharmacokinetic population included the per-protocol population. The safety population included all subjects who received one or more doses of the study drug. Time to maximum plasma concentration of intravenous posaconazole coincided with the end of infusion; the half-life (t½) was 25.76h. Geometric mean (% coefficient of variation) values of area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) and maximum plasma concentration (Cmax) were 59,925 (36.2%) h·ng/mL and 3999 (28.5%) ng/mL, respectively. The posaconazole tablet had a time to maximum plasma concentration of 4h and a t½ of 25.21h after fasting. Geometric mean (coefficient of variation) values of AUC0-∞ and Cmax were 25,263 (39.9%) h·ng/mL and 674.5 (29.6%) ng/mL, respectively. Standard high-fat breakfast increased the exposure of posaconazole approximately twofold with geometric mean ratios (high-fat breakfast/fasted) for AUC0-∞ and Cmax of 2.06 (90% confidence interval 1.86-2.30) and 1.95 (90% confidence interval 1.65-2.31), respectively. The geometric mean absolute bioavailability of the tablet formulation was 42.2% in the fasted state and 87.1% under high-fat breakfast conditions. The most commonly reported adverse events were nausea, vomiting, dizziness, and first-degree atrioventricular block for intravenous posaconazole 300mg and nausea for oral posaconazole 300mg (high-fat breakfast). All adverse events were mild and resolved without sequelae. Posaconazole was generally well tolerated in healthy Chinese male and female subjects. The safety and the high-fat breakfast and fasted pharmacokinetics of posaconazole in healthy Chinese subjects are within exposures demonstrated to be generally well tolerated and efficacious and compare reasonably well with the overall posaconazole data across Western countries.

This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar (RD12014) compared to reference liraglutide (Victoza) in healthy Chinese male subjects, so as to provide the basis for the similarity evaluation of the two drugs. Eligible subjects were randomized 1:1 to two sequences (RD12014‐Victoza or Victoza‐RD12014). Subjects received a single 0.6 mg dose of Victoza or RD12014 by abdominal subcutaneous injection during the first period. After a 7‐day washout period, subjects received the alternative drug during the second period. Blood samples were collected at predefined timepoints for PKs and immunogenicity assessment. The primary PK end points were maximum plasma concentration (C max) and area under the concentration‐time curve from time zero to the time of the last quantifiable concentration (AUC0−last). PK bioequivalence was achieved, if the 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of C max and AUC0−last were within the range of 80.00–125.00%. Safety was assessed throughout the study. The 90% CIs of the GMR of RD12014 to Victoza for C max and AUC0−last were completely within the range of 80.00–125.00%. Thirteen treatment‐related adverse events (TRAEs) were reported in 11 subjects (22.4%) in the RD12014 group, compared to 12 TRAEs reported in 12 subjects (24.5%) in the Victoza group. The blood samples of 49 subjects were negative for anti‐drug antibody and the neutralizing antibody was not further detected. This study demonstrated PK similarity of RD12014 to Victoza in healthy Chinese male subjects. Safety and immunogenicity profiles were comparable between the two groups.

To evaluate the safety and pharmacokinetics of olaparib tablet test formulation (T) and reference formulation (R) in healthy Chinese male subjects. This was a single-dose, randomized-sequence, two-way crossover study including three parts: part A: a safety exploration design in lower dose (n = 14, 100 mg), part B: a pivotal comparative pharmacokinetic (PK) trial under fast condition (n = 44, 150 mg) and part C: a pivotal comparative PK trial under food condition (n = 44, 150 mg). Blood samples were collected for 72hours and the PK parameters of Cmax, AUC0-t, and AUC0-∞ were used to evaluate PK differences. PK analysis of the two olaparib formulations showed that the Geometric Least Squares Mean (GLSM) ratio 90% confidence intervals for pivotal fasting Cmax, AUC0-t, and AUC0-∞ were 94.82-108.97%, 92.94-104.28%, and 92.81-103.85%, respectively, and pivotal fed Cmax, AUC0-t, and AUC0-∞ were 82.78-100.97%, 91.59-104.67%, and 92.17-104.76%, respectively. The 90% confidence interval of the two preparations, Cmax, AUC0-t, and AUC0-∞, all fall within the equivalent range of 80-125%. Both olaparib tablet formulations were well tolerated, with no serious adverse events (SAE) or adverse events (AE) causing withdrawal occurred. Two types of olaparib tablets were bioequivalent under both fasting and fed condition, and were generally well tolerated in healthy Chinese male subjects.

Golimumab is an anti-tumor necrosis factor-α human immunoglobulin G1κ monoclonal antibody that is efficacious for the treatment of moderate to severe rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis in adults. The objective of this study was to assess the pharmacokinetic characteristics of golimumab in healthy male Chinese subjects following a single subcutaneous (SC) administration of golimumab 50 or 100 mg. The safety, tolerability, and immunogenicity of a single SC administration of golimumab in Chinese subjects were also evaluated. This was a phase I, randomized, open-label, single-dose, single-period, single-center study. Twenty-four healthy male Chinese subjects were randomized (1:1) to receive a single SC administration of golimumab 50 or 100 mg. Serial blood samples for the measurement of serum golimumab concentrations were collected and analyzed using a validated electrochemiluminescent immunoassay method. The pharmacokinetic parameters [maximum observed serum concentration (C(max)), time to reach C(max) (t(max)), area under the serum concentration-time curve from time zero to infinity (AUC∞), and terminal half-life (t(½))] of golimumab were derived using a noncompartmental analysis. Following a single SC administration of golimumab 50 or 100 mg in Chinese male subjects (age 19-41 years, body weight 60-76 kg), mean ± standard deviation C(max) (3.6 ± 1.6 and 7.5 ± 1.4 μg/mL, respectively) and AUC∞ (59.8 ± 19.8 and 132.8 ± 27.0 μg·day/mL, respectively) increased in a dose-proportional manner. The median t(max) was in the range of 4.5-5.0 days, and the mean t(½) was in the range of 10.8-11.9 days. Among 24 subjects, 23 had appropriate samples for evaluation of antibodies to golimumab, and one subject (1/23, 4.3%) in the 100-mg group tested positive. Three mild adverse events were reported (infected sebaceous cyst, upper respiratory tract infection, and headache), all in the 50-mg group; none were considered to be related to the study agent. Golimumab exhibited linear pharmacokinetics at dose levels of 50 and 100 mg following a single SC administration in healthy Chinese subjects. Single SC administrations of golimumab 50 or 100 mg were considered to be generally well tolerated. The results from this study indicate that there are no apparent ethnic differences in the pharmacokinetics of golimumab between Chinese and Caucasian subjects.

Nivolumab (Opdivo®) is the first anti-PD-1 antibody approved in the world. LY01015 is a potential biosimilar of nivolumab. This phase I study aimed to establish the pharmacokinetic equivalence between LY01015 and the original investigational nivolumab (Opdivo®) in healthy Chinese male subjects. Additionally, safety and immunogenicity were assessed. A randomized, double-blind, parallel-controlled, phase I trial was conducted with 176 healthy male adults receiving a single intravenous infusion of LY01015 or nivolumab at 0.3mg/kg. Pharmacokinetics, safety, and immunogenicity were evaluated over a 99-day period. The primary pharmacokinetics endpoint was AUC0-∞, and the secondary pharmacokinetic endpoints included AUC0-t and Cmax. Pharmacokinetic bioequivalence was confirmed using standard equivalence margins of 80.00-125.00%. This study is the first to report on the pharmacokinetics, safety, and immunogenicity of Opdivo® in healthy individuals. The pharmacokinetics profiles of LY01015 and Opdivo® were found to be comparable. The geometric mean ratios (90% confidence intervals) for the AUC0-∞, AUC0-t, and Cmax of LY01015 to Opdivo® were 94.49% (90.29-98.88%), 94.92% (88.73-101.54%), and 96.55% (93.32-99.90%), respectively, falling within the conventional bioequivalence criteria of 80.00-125.00%. The safety and immunogenicity were also comparable between the two groups. LY01015 demonstrated highly similar pharmacokinetics to nivolumab in healthy Chinese male subjects. Both drugs exhibited comparable safety and immunogenicity profiles. This trial is registered at the Chinese Clinical Trial Registry website ( https://www.chictr.org.cn/ #ChiCTR2200064771).

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 C max, 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.

Influence of genetic polymorphisms on the pharmacokinetics of celecoxib and its two main metabolites in healthy Chinese subjects

Pharmacokinetic and Pharmacodynamic Interactions Between Henagliflozin, a Novel Selective SGLT-2 Inhibitor, and Warfarin in Healthy Chinese Subjects