Pharmacokinetics and safety of a new generic lurasidone: a phase I bioequivalence study in healthy Chinese subjects.

Latuda® is a novel antipsychotic drug for schizophrenia and bipolar depression. A bioequivalence trial was performed to investigate the bioequivalence of Latuda® and its generic drug lurasidone. Two independent trials were carried out, each involving 28 subjects. In the fasting trial, subjects were randomly assigned to two groups (1:1 ratio), receiving either 40 mg of generic lurasidone or Latuda®. After a 7-day washout period, subjects entered the second period with a crossover administration of 40 mg of generic lurasidone or Latuda®. The postprandial study design was similar to that of the fasting study. In the fasting study, the pharmacokinetic (PK) parameter values of generic lurasidone and Latuda® were as follows: the Cmax was 28.84 ± 19.34 ng/ml and 28.22 ± 21.19 ng/ml, respectively; the AUC0-t was 121.39 ± 58.47 h*ng/ml and 118.35 ± 52.24 h*ng/ml, respectively; and the AUC0-∞ was 129.63 ± 63.26 h*ng/ml and 126.59 ± 57.99 h*ng/ml, respectively. The primary pharmacokinetic parameter, Cmax, was assessed for equivalence using reference-scaled average bioequivalence (RSABE), while other parameters (AUC0-t, AUC0-∞) were evaluated using average bioequivalence (ABE). The results indicate that both Cmax and AUC meet the equivalence criteria. In the postprandial study, the PK values of generic lurasidone and Latuda® were as follows: the Cmax was 74.89 ± 32.06 ng/ml and 83.51 ± 33.52 ng/ml, respectively; the AUC0-t was 274.77 ± 103.05 h*ng/ml and 289.26 ± 95.25 h*ng/ml, respectively; and the AUC0-∞ was 302.44 ± 121.60 h*ng/ml and 316.32 ± 109.04 h*ng/ml, respectively. The primary pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞) were assessed for equivalence using ABE, and both met the equivalence criteria. In the study, lurasidone and Latuda® both exhibited acceptable safety and tolerability. The results displayed that lurasidone and Latuda® were bioequivalent and safe in healthy Chinese participants. Clinical Trial Registry: This trial is registered at chinadrugtrials.org.cn (no.: CTR20191717, date: 2019.08.29).

Pharmacokinetics and bioequivalence of sunitinib and Sutent® in Chinese healthy subjects: an open-label, randomized, crossover study.

Purpose: The purpose of this study was to examine the pharmacokinetics (PK), bioequivalence and safety of generic sunitinib and its original product Sutent® in healthy Chinese subjects through a phase-I clinical trial. Methods: The study selected two groups of 24 healthy Chinese subjects in a 1:1 ratio through random allocation. Each participant received either 12.5 mg of sunitinib or Sutent® per cycle. A total of 15 different time points were employed for blood sample collection during each cycle. Furthermore, a comprehensive assessment of the drugs' safety was consistently maintained throughout the trial. Results: The average adjusted geometric mean ratios (GMR) (90% CI) for the primary PK parameters Cmax, AUC0-t and AUC0-∞ were 97.04% (93.06%-101.19%), 98.45% (93.27%-103.91%) and 98.22% (93.15%-103.56%), respectively. The adjusted GMRs for essential pharmacokinetic (PK) parameters all met the requirements for bioequivalence, with values within the acceptable range of 80%-125%. In addition, the two drugs showed comparable results for the other PK parameters. These results indicate that the two drugs were bioequivalent. Furthermore, both drugs showed well safety. Conclusion: The research results proved that the PK and safety profiles of sunitinib in healthy Chinese subjects were comparable to those of Sutent®. These results advocate the clinical application of generic sunitinib as a potential alternative to original product Sutent® in the treatment of certain medical conditions.

A randomized, single-blind, single-dose, parallel-group study in healthy subjects to demonstrate the pharmacokinetic equivalence of trastuzumab and its biosimilar.

BACKGROUND: Trastuzumab is a humanized anti-HER2 monoclonal antibody used in the treatment of breast cancer. This study compared the pharmacokinetics (PK), immunogenicity and safety of trastuzumab (Roche Pharma AG) and its biosimilar (Chia Tai Tianqing Pharmaceutical Group Co. Ltd) in healthy Chinese subjects. RESEARCH DESIGN AND METHODS: A randomized, parallel, double-blind, single-dose study was conducted. Healthy male subjects were randomized to receive trastuzumab (n = 43) or its biosimilar (n = 43) intravenously at a dose of 4 mg. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and PK parameters were statistically analyzed. Safety and immunogenicity were also evaluated. RESULTS: The geometric mean ratios (GMRs) of AUC0-t, Cmax and AUC0-∞ for trastuzumab and its biosimilar were 92.3%, 100.77% and 92.2%, respectively. The 90% CIs were all within 80%-125%, meeting the bioequivalence standards. No serious adverse events or immunogenicity were reported, and all the adverse events reported were mild and similar between the two treatment groups. CONCLUSIONS: Trastuzumab was well tolerated, showed a similar safety profile to its biosimilar, and demonstrated PK equivalence. CLINICAL TRIAL REGISTRATION: This trial was registered at the [anonymized].

Comparing the bioequivalence and safety of liraglutide in healthy Chinese subjects: an open, single-dose, randomized, repeated, two-sequence, two-cycle phase I clinical trial.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone. Liraglutide, a GLP-1 receptor agonist, can lower blood sugar by increasing insulin production and inhibiting the production of glucagon. This study researched the bioequivalence and safety of the test and reference drugs in healthy Chinese subjects. RESEARCH DESIGN AND METHODS: Subjects (N = 28) were randomly divided into group A and group B at a ratio of 1:1 for a two-cycle cross-over study. There was single dose per cycle with subcutaneous injection of the test and reference drugs, respectively. The washout was set at 14 days. Plasma drug concentrations were detected by specific liquid chromatography and tandem mass spectrometry (LC-MS/MS) assays. Statistical analysis of major pharmacokinetic (PK) parameters was conducted to assess drug bioequivalence. In addition, we evaluated the safety of the drugs throughout the trial. RESULTS: The geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ for the test and reference drugs were 107.11%, 106.56%, 106.09%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both had good safety in this study. CONCLUSION: The study shows that the two drugs had similar bioequivalence and safety. CLINICAL TRIAL REGISTRATION: DCTR: CTR20190914; ClinicalTrials.gov: NCT05029076.

Pharmacokinetics and safety of dasatinib and its generic: a phase I bioequivalence study in healthy Chinese subjects.

BACKGROUND: Dasatinib (Sprycel®) is a tyrosine kinase inhibitor for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. RESEARCH DESIGN & METHODS: We designed a clinical study to demonstrate that the dasatinib tablet (YiNiShu®) (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Dasatinib (Bristol Myers Squibb) were bioequivalent under fasting and fed conditions. The whole study was structured into the fasting trial and the postprandial trial. Each period, subjects were given 50 mg dasatinib or its generic. The RSABE (reference scale average bioequivalence) and ABE (average bioequivalence) methods were employed to assess bioequivalence by pharmacokinetics (PK) parameters for a highly variable drug. RESULTS: 32 and 24 eligible volunteers were enrolled in the fasting and postprandial trials, respectively. In the fasting trial, the RSABE method was performed, and point estimates of Cmax, AUC0-t, and AUC0-∞ met the bioequivalence criteria. In the postprandial trial, the ABE method was performed, and the 90% CI of the geometric mean ratio (GMR) for PK parameters met the requirements of bioequivalence standards. CONCLUSION: The results proved that the PK parameters of the two drugs were similar and bioequivalent, indicating that both drugs had a good safety profile. CLINICAL TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov (Number: NCT05640804) and Drug Clinical Trial Registration and Information Disclosure Platform (Number: CTR20181708).

A randomized, open-label, two-cycle, two-crossover phase I clinical trial comparing the bioequivalence and safety of afatinib and Giotrif® in healthy Chinese subjects.

OBJECTIVE: Afatinib is an oral, irreversible ErbB family blocker. It binds covalently to the kinase domains of epidermal growth factor (EGFR), HER2 and HER4, resulting in irreversible inhibition of tyrosine kinase autophosphorylation. Our trial compared the bioequivalence and safety between afatinib produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. and Giotrif® produced by Boehringer Ingelheim. METHODS: Healthy Chinese subjects (N = 36) were randomly divided into two groups at a ratio of 1:1. There was a single dose per period of afatinib and Giotrif®. The washout was set as 14 days. Plasma drug concentrations of afatinib and Giotrif® were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Statistical analysis of major pharmacokinetic (PK) parameters was conducted to assess drug bioequivalence. In addition, we evaluated the safety of the drugs throughout the trial. RESULTS: The geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ for afatinib and Giotrif® were 102.80%, 101.83%, and 101.58%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both drugs showed a good safety profile during the trial. CONCLUSION: This study showed that afatinib was bioequivalent to Giotrif® in healthy Chinese subjects with well safety. CHINESE CLINICAL TRIAL REGISTRY: This trial is registered at the Chinese Clinical Trial website ( http://www.chinadrugtrials.org.cn/index.html # CTR20171160).

Pharmacokinetics and safety of the two oral cefaclor formulations in healthy chinese subjects in the fasting and postprandial states.

We conducted a phase I bioequivalence trial in healthy Chinese subjects in the fasting and postprandial states. The goal of this trial was to compare the pharmacokinetics and safety of the test preparation Cefaclor granule (Disha Pharmaceutical Group Co., Ltd.) and the reference preparation Cefaclor suspension (Ceclor®, Eli Lilly and Company). In this trial, 24 subjects were selected in the fasting and postprandial states, respectively. Enrolled subjects randomly accepted a single dose of 0.125 g Cefaclor granule or Cefaclor suspension. The washout period was set as 2 days. Blood samples were collected within 8 h after administration in the fasting state and within 10 h after administration in the postprandial state. Plasma concentrations were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters (AUC, Cmax) were used to evaluate bioequivalence of the two drugs. In the fasting trial, the geometric mean ratios (90% confidence intervals CIs) for Cmax, AUC0-t, and AUC0-∞ were 93.01% (85.96%-100.63%), 97.92% (96.49%-99.38%) and 97.95% (96.52%-99.41%), respectively. The GMR (90% CIs) for Cmax, AUC0-t, and AUC0-∞ in postprandial state were 89.27% (81.97%-97.22%), 97.31% (95.98%-98.65%) and 97.31% (95.93%-98.71%), respectively. The 90% CIs of AUC and Cmax in the fasting and postprandial states were within the 80-125% bioequivalence range. Therefore, Cefaclor granule and Cefaclor suspension were bioequivalent and displayed similar safety profiles. Furthermore, food intake affected the pharmacokinetic parameters of both drugs.

A randomized, double-blind, single-dose, parallel phase I clinical trial to compare the bioequivalence, immunogenicity, and safety of bevacizumab biosimilar and bevacizumab in healthy Chinese subjects.

BACKGROUND: Bevacizumab, a humanized monoclonal antibody against VEGF, can be used as a target therapy for colorectal cancer. A phase I clinical trial was conducted to compare the bioequivalence, immunogenicity, and safety of bevacizumab biosimilar (Chia Tai Tianqing Pharmaceutical Group Co., Ltd.) and Bevacizumab (Roche Diagnostics GmbH) in healthy Chinese males. RESEARCH DESIGN & METHOD: Healthy Chinese subjects (N = 98) were randomly divided into two groups. A single-dose bevacizumab biosimilar or Bevacizumab was given per cycle. Plasma drug concentrations were detected by liquid chromatography-tandem mass spectrometry (LC-MC/MS) assay. We detected the levels of anti-drug antibody (ADA) to evaluate drug immunogenicity and the safety of drugs throughout the study. RESULTS: The geometric mean ratios (GMRs) of AUC0-t, Cmax, and AUC0-∞ for bevacizumab biosimilar and Bevacizumab were 96.27%, 93.69%, and 97.01%, respectively. The 90% CIs were all within 80-125%, meeting the bioequivalence standards. The levels of ADA were similar. In addition, the two drugs both demonstrated excellent safety in the trial. CONCLUSION: This study showed that bevacizumab biosimilar and Bevacizumab had similar pharmacokinetics (PK) parameters and safety in healthy Chinese subjects.

A randomized, crossover, phase I clinical study to evaluate bioequivalence and safety of tofacitinib and Xeljanz® in Chinese healthy subjects.

OBJECTIVE: Tofacitinib is an oral Janus kinase (JAK) inhibitor that has been marketed and approved in the USA for the clinical treatment of rheumatoid arthritis, psoriasis and other inflammatory and autoimmune diseases. A phase I clinical trial was conducted to compare the bioequivalence and safety of tofacitinib (Chia Tai Tianqing Pharmaceutical Group Co., Ltd.) and Xeljanz® (Pfizer Inc.) in healthy Chinese subjects, providing basis for the clinical application of tofacitinib. METHODS: Healthy Chinese subjects (N = 32) were randomly assigned to two groups at a 1:1 ratio. Subjects orally took 5 mg tofacitinib or Xeljanz® per cycle in random sequence. Blood samples were collected at 15 sampling points per cycle, and plasma drug concentrations of tofacitinib or Xeljanz® were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and statistical analysis for the pharmacokinetic (PK) parameters. Subjects' physical indicators were monitored during the whole process to evaluate drug safety. RESULTS: The adjusted geometric mean ratios (GMRs) of the peak concentration (Cmax), area under the curve (AUC) from time zero to the last measurable concentration (AUC0-t) and AUC from time zero to observed infinity (AUC0-∞) were all within the range of 80-125%. The other PK parameter values were similar. The above values were all meeting the bioequivalence criteria with well safety. CONCLUSION: The pharmacokinetic parameters and safety profile of tofacitinib were similar to those of Xeljanz® in healthy Chinese subjects. Therefore, tofacitinib can be considered bioequivalent to Xeljanz®, and the findings of this trial will promote the clinical application of tofacitinib.

A randomized, open-label, single-dose, two-cycle crossover study to evaluate the bioequivalence and safety of lenvatinib and Lenvima® in Chinese healthy subjects.

BACKGROUND: Lenvatinib is a tyrosine kinase receptor inhibitor that inhibits vascular and endothelial growth factor receptor kinase activity. This study evaluated the bioequivalence and safety of lenvatinib with Lenvima® . RESEARCH DESIGN AND METHODS: The fasting and postprandial groups were two independent trials. Subjects were randomly divided into two sequences at a ratio of 1:1 for two-cycle crossover administration. Subjects took 10 mg lenvatinib or Lenvima® once per cycle. The wash-out period was 14 days. Detected the plasma drug concentrations and assessed the bioequivalence of two drugs. Besides, we evaluated the safety of the drugs throughout the trial. RESULTS: In the fasting state, the GMRs of Cmax, AUC0-t, and AUC0-∞ were 99.89%, 102.98% and 103.19%, respectively. The 90% CIs were all within 80%-125%. In the postprandial state, the GMRs of Cmax, AUC0-t, and AUC0-∞ were 98.96%, 94.25% and 95.27%, respectively. The 90% CIs were all within 80%-125%. All results met the bioequivalence criteria. Both drugs had good safety and tolerance in this trial. CONCLUSION: This study showed that lenvatinib and Lenvima® had similar bioequivalence and safety in healthy Chinese subjects under fasting and postprandial conditions. CLINICAL TRIAL REGISTRATION: This trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html # CTR20191172).

A randomized, double-blind, single-dose, single-center, parallel phase I clinical study comparing the pharmacokinetics, immunogenicity, safety, and tolerance of pertuzumab injection and Perjeta® in healthy Chinese male subjects.

BACKGROUND: Perjeta® is a recombinant, humanized monoclonal antibody that has been marketed and approved for the targeted therapy of human epidermal growth factor receptor (HER2) positive breast cancer in the United States. This study compared the bioequivalence, immunogenicity, and safety of pertuzumab injection (a biosimilar of Perjeta® produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Perjeta® (produced by Roche Pharma AG) in healthy Chinese males. RESEARCH DESIGN AND METHODS: Healthy Chinese male subjects (N = 87) were randomly given intravenous injection of 5 mg/kg pertuzumab or Perjeta® at a 1:1 ratio. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay, and primary pharmacokinetic parameters were statistically analyzed. We detected the levels of anti-drug antibody (ADA) and neutralizing antibody (nAb) to evaluate drug immunogenicity and safety of the drugs throughout the study. RESULTS: The geometric mean ratios of AUC0-t, Cmax, and AUC0-∞ for pertuzumab and Perjeta® were 100.42%, 96.71%, and 101.47%, respectively. The 90% CIs were all within 80%-125%, meeting the bioequivalence standards. The levels of ADA and nAb were similar. In addition, both had good safety in the study. CONCLUSION: The study shows that pertuzumab injection and Perjeta® had similar bioequivalence, immunogenicity, and safety.