Pharmacokinetics, Safety, and Tolerability of Tenapanor in Healthy Chinese and Caucasian Volunteers: A Randomized, Open-Label, Single-Center, Placebo-Controlled Phase 1 Study.

Background: Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium/phosphorus and fluid overload in various cardiac-renal diseases, which has been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects.

Methods: This randomized, open-label, single-center, placebo-controlled phase 1 study (https://www.

Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults.

Background And Objectives: This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor.

Methods: This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal.

Model-informed dose selection for an investigational human epidermal growth factor receptor 2 antibody-drug conjugate FS-1502 in patients with human epidermal growth factor receptor 2-expressing advanced malignant solid tumours.

Aims: The dose-escalation phase (phase Ia study) of a novel human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) FS-1502 included a dose range from 0.1 to 3.5 mg/kg in HER2-expressing advanced malignant solid tumours.

Avatrombopag for adult chronic primary immune thrombocytopenia: a randomized phase 3 trial in China.

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder with decreased platelet counts and increased bleeding risk.

Objectives: To evaluate the efficacy and safety of avatrombopag, a second-generation oral thrombopoietin receptor agonist, for the treatment of Chinese patients with chronic primary ITP.

Methods: This multicenter, randomized, double-blind, placebo-controlled phase 3 study (CTR20210431) consisted of a 6-week double-blind core treatment phase followed by a 20-week, open-label extension phase.

Phase 1 dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of FCN-159 in adults with neurofibromatosis type 1-related unresectable plexiform neurofibromas.

Background: Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN.

Effect of Food (Low and High Fat) on Pharmacokinetics of FCN-159, a Selective MEK Inhibitor, in Healthy Chinese Males.

Introduction: FCN-159 is a novel, oral, potent, selective MEK1/2 inhibitor in clinical development for the treatment of NRAS-mutant advanced melanoma and neurofibromatosis type 1. We investigated the effect of food on the pharmacokinetics (PK), safety, and tolerability of FCN-159.

Methods: In this single-center, open-label, phase 1 study with a three-period, three-sequence, crossover design, healthy Chinese male subjects (n = 24) were randomized (1:1:1) to receive a single, oral 8 mg dose of FCN-159 in the fasted state (overnight, > 10 h), and with a low-fat and a high-fat meal, separated by a 10-day washout.

A Phase I Dose-Escalation and Dose-Expansion Study of FCN-437c, a Novel CDK4/6 Inhibitor, in Patients with Advanced Solid Tumors.

A phase I study evaluated the safety, tolerability, and maximum-tolerated dose (MTD)/recommended phase II dose (RP2D) of FCN-437c, a novel, orally available cyclin-dependent kinase inhibitor (CDK4/6i), in participants with advanced/metastatic solid tumors (aSTs). FCN-437c was escalated from 50 mg (once daily [QD] on days 1-21 of 28-day cycles) to the MTD/RP2D. In the dose-expansion phase, patients with CDK4/6i-treated breast cancer, or -mutant () non-small-cell lung cancer (NSCLC) received the MTD.

Immunogenicity and safety of BNT162b2 mRNA vaccine in Chinese adults: A phase 2 randomised clinical trial.

Background: BNT162b2, an mRNA vaccine against COVID-19, is being utilised worldwide, but immunogenicity and safety data in Chinese individuals are limited.

Methods: This phase 2, randomised, double-blind, placebo-controlled trial included healthy or medically stable individuals aged 18-85 years enrolled at two clinical sites in China. Participants were stratified by age (≤55 or >55 years) and randomly assigned (3:1) by an independent randomisation professional to receive two doses of intramuscular BNT162b2 30 μg or placebo, administered 21 days apart.

A first-in-human, phase 1a dose-escalation study of the selective MEK1/2 inhibitor FCN-159 in patients with advanced NRAS-mutant melanoma.

Background: A phase 1a first-in-human study evaluated the safety/tolerability, preliminary antitumour activity and pharmacokinetics of the oral MEK1/2 inhibitor FCN-159 in Chinese patients with advanced, NRAS-mutant melanoma.

Patients And Methods: Patients received a single FCN-159 dose at assigned levels, proceeding to continuous dosing (once daily [QD] for 28-day cycles) if no dose-limiting toxicities (DLTs) occurred within the next 3 days. Dose escalation was initiated after review of data for the previous dose level.

The Delivery of mRNA Vaccines for Therapeutics.

mRNA vaccines have been revolutionary in combating the COVID-19 pandemic in the past two years. They have also become a versatile tool for the prevention of infectious diseases and treatment of cancers. For effective vaccination, mRNA formulation, delivery method and composition of the mRNA carrier play an important role.

Avatrombopag ethnic sensitivity analysis in chronic liver disease and thrombocytopenia patients: individual-level pooled analysis.

Introduction: Few data have been published on the ethnic sensitivity of effectiveness, pharmacokinetics (PK), and pharmacodynamics (PD) of avatrombopag for the management of thrombocytopenia in patients with chronic liver disease (CLD).

Methods: An ethnic sensitivity analysis was performed based on the results from two phase III studies (ADAPT-1 and ADAPT-2), with a primary endpoint of the proportion of patients without the requirement of platelet transfusion or rescue treatment for bleeding after randomization to 7 days following a scheduled procedure, and three phase I studies in healthy subjects. Cochran-Mantel-Haenszel and Fisher's exact tests were used to compare the differences in effectiveness in different ethnicities and overall population.

Immune Persistence and Safety After SARS-CoV-2 BNT162b1 mRNA Vaccination in Chinese Adults: A Randomized, Placebo-Controlled, Double-Blind Phase 1 Trial.

Introduction: BNT162b1 is a lipid nanoparticle-formulated, nucleoside-modified mRNA SARS-CoV-2 vaccine. Here, we report safety and immune persistence data following a primary two-dose vaccination schedule administered 21 days apart.

Methods: Immune persistence was determined at month 3 in 72 younger participants (aged 18-55 years) and at month 6 in 70 younger and 69 older participants (aged 65-85 years).

Ethnicity evaluation of ferric pyrophosphate citrate among Asian and Non-Asian populations: a population pharmacokinetics analysis.

Purpose: To evaluate the potential ethnic differences of ferric pyrophosphate citrate (FPC, Triferic) in healthy subjects and patients with hemodialysis-dependent stage 5 chronic kidney disease (CKD-5HD) and identify covariates that may influence pharmacokinetics (PK) of FPC.

Methods: Data were collected from 2 Asian and 4 non-Asian clinical studies involving healthy subjects and CKD-5HD patients. Three population PK models were developed: M1 for intravenous (IV) administration of FPC in healthy subjects; M2 for dialysate administration of FPC in CKD-5HD patients; M3 for pre-dialyzer administration of FPC in CKD-5HD patients.

Safety and pharmacokinetic profile of pretomanid in healthy Chinese adults: Results of a phase I single dose escalation study.

We investigated the safety, tolerability and pharmacokinetic (PK) profile of pretomanid (formerly PA-824) in healthy Chinese volunteers. This was a single-center, double-blind, placebo-controlled, phase I dose escalation study, in which healthy volunteers were consecutively allocated to increasing pretomanid dose groups (50, 100, 200, 400, 600, 800, or 1000 mg) and randomized to receive pretomanid or matching placebo. The primary objective was to evaluate the safety, tolerability and PK profile of pretomanid.

The paradigm shift in treatment from Covid-19 to oncology with mRNA vaccines.

mRNA vaccines have gained popularity over the last decade as a versatile tool for developing novel therapeutics. The recent success of coronavirus disease (COVID-19) mRNA vaccine has unlocked the potential of mRNA technology as a powerful therapeutic platform. In this review, we apprise the literature on the various types of cancer vaccines, the novel platforms available for delivery of the vaccines, the recent progress in the RNA-based therapies and the evolving role of mRNA vaccines for various cancer indications, along with a future strategy to treat the patients.

Pharmacokinetics and Safety of Ferric Pyrophosphate Citrate in Chinese Subjects with and without Hemodialysis-Dependent Stage 5 Chronic Kidney Disease.

Background And Objective: Anemia caused by iron depletion is common in patients with hemodialysis-dependent stage 5 chronic kidney disease (CKD-5HD) patients. To maintain the iron levels, external administration of iron is essential. Ferric pyrophosphate citrate (FPC) is a novel, water-soluble complex iron salt.

A phase I study of FCN-411, a pan-HER inhibitor, in EGFR-mutated advanced NSCLC after progression on EGFR tyrosine kinase inhibitors.

Background: There are no approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-small cell lung cancer (NSCLC) without EGFR T790M mutation after progression on first- or second-generation EGFR-TKIs.

Methods: We conducted this phase I, open-label, multicenter, dose-escalation/dose-expansion study to evaluate the safety, tolerability, antitumor activity, and pharmacokinetics of FCN-411, a TKI targeting EGFR, HER2, and HER4, in patients with EGFR-mutated advanced NSCLC whose disease had progressed during treatment of EGFR-TKIs. Adult patients with stage IIIB-IV NSCLC harboring EGFR mutations (exon 18/19/20/21) who had progressed on prior EGFR-TKIs were enrolled.

Review of Ribosome Interactions with SARS-CoV-2 and COVID-19 mRNA Vaccine.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causing pathogen of the unprecedented global Coronavirus Disease 19 (COVID-19) pandemic. Upon infection, the virus manipulates host cellular machinery and ribosomes to synthesize its own proteins for successful replication and to facilitate further infection. SARS-CoV-2 executes a multi-faceted hijacking of the host mRNA translation and cellular protein synthesis.

Pharmacokinetics, Pharmacodynamics, and Tolerability of Opicapone in Healthy Chinese and Caucasian Subjects: An Open-Label, Single-Center, Phase 1 Study.

Introduction: This study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple doses of opicapone (OPC) in healthy Chinese and Caucasian subjects.

Methods: In this open-label, single-center, phase 1 study, eligible Chinese subjects received one of three OPC doses (25, 50, or 100 mg), and Caucasian subjects received either 25 or 50 mg of OPC. All subjects were administered a single dose of OPC, whereas subjects in the 50-mg OPC group continued to receive once-daily doses of 50 mg OPC for 10 days.

The Development of mRNA Vaccines for Infectious Diseases: Recent Updates.

mRNA-based technologies have been of interest for the past few years to be used for therapeutics. Several mRNA vaccines for various diseases have been in preclinical and clinical stages. With the outbreak of the COVID-19 pandemic, the emergence of mRNA vaccines has transformed modern science.

Phase 1a study of the CDK4/6 inhibitor, FCN-437c, in Chinese patients with HR + /HER2- advanced breast cancer.

Purpose This phase 1a, first-in-human study assessed the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), and antitumor activity of FCN-437c, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Methods The study enrolled female patients with HR + /HER2- advanced breast cancer (BC) who failed standard of care therapy. A 3 + 3 dose-escalation design was utilized with a starting dose of 50 mg daily for 3 weeks on and 1 week off treatment in 28-day cycles.

BNT162b2 Vaccine Encoding the SARS-CoV-2 P2 S Protects Transgenic hACE2 Mice against COVID-19.

BNT162b2 is a highly efficacious mRNA vaccine approved to prevent COVID-19. This brief report describes the immunogenicity and anti-viral protective effect of BNT162b2 in hACE2 transgenic mice. Prime-boost immunization with BNT162b2 elicited high titers in neutralizing antibodies against SARS-CoV-2, which correlated with viral clearance and alleviated lung lesions in these mice after viral challenge.

Safety and immunogenicity of the SARS-CoV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomized, placebo-controlled, double-blind phase 1 study.

An effective vaccine is needed to end the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we assess the preliminary safety, tolerability and immunogenicity data from an ongoing single-center (in Jiangsu province, China), parallel-group, double-blind phase 1 trial of the vaccine candidate BNT162b1 in 144 healthy SARS-CoV-2-naive Chinese participants. These participants are randomized 1:1:1 to receive prime and boost vaccinations of 10 µg or 30 µg BNT162b1 or placebo, given 21 d apart, with equal allocation of younger (aged 18-55 years) and older adults (aged 65-85 years) to each treatment group (ChiCTR2000034825).