Safety, tolerability, and pharmacokinetics of single and multiple ascending Oral doses of DA-8010 in healthy subjects: First-in-human phase I study.

This study assessed the safety, tolerability, and pharmacokinetics of single and multiple oral doses of DA-8010, a muscarinic M receptor antagonist, in healthy subjects. This was a randomized, double-blind, placebo-controlled, ascending single (Part A: 1, 2.5, 5, 20, and 40 mg QD fasted and 10 mg QD fasted and fed) and multiple doses (Part B: 5, 10, and 20 mg QD from Days 1 to 7 fasted), sequential-group study.

Effect of mild or moderate hepatic impairment on the pharmacokinetics of risdiplam.

Aim: This phase I, multicentre, open-label, nonrandomised, parallel-group, two-part study aimed to evaluate the effect of mild to moderate hepatic impairment on the pharmacokinetics (PK), safety and tolerability of a single oral dose of risdiplam.

Methods: Adult subjects (aged 18-70 years) with mild (Child-Pugh Class A; Part 1) or moderate (Child-Pugh Class B; Part 2) hepatic impairment were matched with subjects with normal hepatic function on sex, age, body mass index and smoking status. Each subject received a single oral dose of 5 mg of risdiplam.

Osimertinib Plus Durvalumab in Patients With EGFR-Mutated, Advanced NSCLC: A Phase 1b, Open-Label, Multicenter Trial.

Introduction: EGFR tyrosine kinase inhibitors (TKIs) are recommended for EGFR-mutated NSCLC treatment. EGFR activation up-regulates programmed death-ligand 1 expression and other immunosuppressive factors in NSCLC, causing immune microenvironment remodeling. Osimertinib (an EGFR TKI) plus durvalumab (programmed death-ligand 1 blockade) was evaluated in the TATTON study (NCT02143466).

Human Safety, Tolerability, and Pharmacokinetics of Molnupiravir, a Novel Broad-Spectrum Oral Antiviral Agent with Activity Against SARS-CoV-2.

Molnupiravir, EIDD-2801/MK-4482, the prodrug of the active antiviral ribonucleoside analog ß-d-N4-hydroxycytidine (NHC; EIDD-1931), has activity against a number of RNA viruses including severe acute respiratory syndrome coronavirus 2, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and seasonal and pandemic influenza viruses.Single and multiple doses of molnupiravir were evaluated in this first-in-human, phase 1, randomized, double-blind, placebo-controlled study in healthy volunteers, which included evaluation of the effect of food on pharmacokinetics.EIDD-1931 appeared rapidly in plasma, with a median time of maximum observed concentration of 1.

A phase 1, randomized, open-label, single-dose study to assess the relative bioavailability of a subcutaneous dose of FKB327 when administered using a prefilled syringe, a prefilled auto-injector, or a vial with disposable syringe in healthy subjects.

Background/objective: FKB327 is a biosimilar of the adalimumab reference product (RP). The primary objective was to assess the relative bioavailability of FKB327 after a single subcutaneous (SC) dose via prefilled syringe (PFS), auto-injector (AI), or vial with a disposable syringe (vial), in healthy subjects.

Methods: This randomized, open-label, parallel-group, single SC-dose study was conducted in 195 healthy male and female subjects who were randomized 1:1:1 to receive FKB327 40 mg via PFS, AI, or vial.

Changes in Biomarkers of Exposure on Switching From a Conventional Cigarette to Tobacco Heating Products: A Randomized, Controlled Study in Healthy Japanese Subjects.

Background: Smoking is a leading cause of numerous human disorders including pulmonary disease, cardiovascular disease, and cancer. Disease development is primarily caused by exposure to cigarette smoke constituents, many of which are known toxicants. Switching smokers to modified risk tobacco products (MRTPs) has been suggested as a potential means to reduce the risks of tobacco use, by reducing such exposure.

A randomised, controlled, two-Centre open-label study in healthy Japanese subjects to evaluate the effect on biomarkers of exposure of switching from a conventional cigarette to a tobacco heating product.

Background: Smoking is a leading cause of numerous human disorders including lung cancer, chronic obstructive pulmonary disease, and atherosclerotic cardiovascular disease. The development of modified risk tobacco products (MRTPs) has been suggested as a possible way to reduce the risks of tobacco smoking by reducing exposure to cigarette smoke toxicants. This study is designed to investigate whether biomarkers of such exposure are reduced when smokers switch from smoking commercial cigarettes to using either a novel or a commercially-available tobacco heating product (THP).

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis.

Background: Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC).

Aim: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC.

Methods: Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days.

Clinical implications of the pharmacology of sertraline.

Sertraline is slowly absorbed after oral administration, with peak plasma concentrations at 6-8 h. Plasma concentrations are linearly related to dose. The elimination half-life is about 32 h; metabolism is by demethylation to an inactive metabolite.

Ethics of evaluation of new drugs in human volunteers.

Experiments in human volunteers are a vital part of the evaluation of most new drugs. Are such experiments ethical? This question is discussed in the light of four ethical principles: justice, beneficence, non-maleficence and respect for autonomy. Problem areas include recruitment of volunteers, obtaining consent, payment for participation and special groups such as students and staff of research institutions, the poor, women of child-bearing potential, children and elderly volunteers.

Piroxicam-beta-cyclodextrin: effects on gastrointestinal blood loss and gastric mucosal appearance in healthy men.

Thirty-six healthy men aged 20-31 years took part in a randomized, double-blind, double-dummy, parallel-group study to compare the effects of repeated doses of piroxicam-beta-cyclodextrin, piroxicam and placebo on faecal blood loss and the endoscopic appearances of gastric and duodenal mucosa. After an initial endoscopy, subjects received on day 0 autologous erythrocytes labelled with 51Cr. Complete daily faecal collections were then made from days 6 to 12.

Lornoxicam, indomethacin and placebo: comparison of effects on faecal blood loss and upper gastrointestinal endoscopic appearances in healthy men.

Forty-five healthy men aged 21-34 years took part in a double-blind, parallel-group, placebo-controlled study of the effects of 28 days' treatment with lornoxicam 4 mg twice daily or indomethacin 50 mg twice daily on faecal blood loss and the endoscopic appearances of gastric and duodenal mucosa. After an initial endoscopic examination, subjects received, intravenously, on day 0, autologous erythrocytes labelled with 51Cr. Complete daily faecal collections were then made from days 6-12, 20-26 and 34-40.

Bisoprolol: studies of potential interactions with theophylline and warfarin in healthy volunteers.

Many patients receiving bisoprolol treatment might also require warfarin or theophylline therapy. Two studies were carried out in healthy volunteers to investigate the possibility that bisoprolol might interact with warfarin or theophylline, both of which have low therapeutic ratios. In a balanced, two-way, crossover study, eight men and four women took bisoprolol 10 mg daily for 14 days.

Renal and gastrointestinal tolerability of lornoxicam, and effects on haemostasis and hepatic microsomal oxidation.

Three separate studies were carried out to assess the renal and gastrointestinal tolerability of lornoxicam, and its effects on haemostasis and hepatic microsomal oxidation. Haemostasis and hepatic microsomal oxidation. Six men and 6 women had salivary antipyrine half-life determined before and on the last day of 14 days' treatment with lornoxicam 4 mg twice daily.

Trazodone conventional and controlled-release formulations: pharmacodynamic effects after single and repeated administration.

In a double-blind study, the pharmacodynamic effects of single and repeated doses of two formulations of trazodone were compared in 14 healthy young volunteers (6 men and 8 women). They received either 100 mg trazodone conventional capsules or 150 mg controlled-release tablets daily at 08.00 hours for two 7-day periods separated by a 'wash-out' period of 2 weeks.