Healthy Volunteer Study

The purpose of this study is to learn about the safety of a new study medicine called PF-08103402 in healthy adults (do not have disease) and or in adults with mild-to-moderate asthma. This is the first time the study medicine is being given to people. For Parts A, B, C, D and F, the study is seeking participants who: * Are healthy (do not have disease) males or females who can no longer have children, * Are 18 to 65 years old, * Have a body mass index (BMI) of 16 to 32 kilograms per meter squared and a body weight of more than 50 kilograms (110 pounds). Body mass index is a way to measure body fat by using a person's height and weight For Part A (optional group or cohort 3: Japanese participants only): * A body weight of more than 45 kilograms (100 pounds). * Have 4 biological Japanese grandparents who were born in Japan. For Part E only: * Adults with a documented history of asthma (confirmed by a doctor) for at least 12 months before entering the study. * Have a body mass index (BMI) of 16 to 35 kilograms per meter squared and a total body weight of more than 50 kilograms (110 pounds). The study has six parts: Part A, Part B, Part C, Part D, Part E and Part F. The study medicine will be taken as a suspension or tablet by mouth 1 time a day (except in Parts B and E where it will be taken 1 time a day for 14 days) at the study clinic. The study will help understand: * how the body processes the study medicine in healthy participants (Parts A and B), * how much of the study medicine gets into the bloodstream and if food affects the amount of study medicine in the blood in healthy participants (Part C), * how the study medicine is broken down and leaves the body in healthy participants (Optional Part D), * how the study medicine is processed in adults with mild-to-moderate asthma (Optional Part E), * if taking the study medicine together with another medicine affects how each medicine is processed by the body in healthy participants (Optional Part F). Participants will take part in the study for about 10 weeks (Parts A and F), 12 weeks (Part B), 9 weeks (Parts C and D), and 16 weeks (Part E). During this time, they will have 2 study visits at the study clinic and up to 28 overnight stays (Part A), 18 overnight stays (Parts B and E), 10 overnight stays (Part C), 11 overnight stays (Part D), and 16 overnight stays (Part F). The study team will also call participants 1 time over the phone at the end of the study to assess how they are doing. Study measurements will be taken by body examination, monitoring side effects, blood and urine tests, heart tests (ECG), vital signs (blood pressure and pulse), questionnaires (Parts C and E), stool samples (Part D only), and breathing tests (Part E only).

Muscle deconditioning, characterized by a loss of muscle mass and strength, is a frequent consequence of prolonged lower limb unloading. Beyond muscle mass loss, reduced neural drive contributes significantly to strength decline, highlighting the need for interventions targeting neuromuscular function during immobilization. Focal muscle vibration (FMV) has shown promise in modulating neuromuscular excitability by activating muscle spindle afferents and inducing cortical adaptations. Chronic use of FMV has been associated with significant strength gains and improved neural command. This makes FMV an effective rehabilitation tool. Its simplicity and non-invasiveness further make it a practical countermeasure.

Preservatives such as m-Cresol are essential components in many subcutaneously injected medications, including insulin or human growth hormone, to prevent bacterial growth. However, clinical reports have suggested that these preservatives may cause local discomfort or pain at the injection site, which can negatively impact treatment adherence. While m-Cresol is widely used, its direct contribution to injection-site pain has not yet been investigated in a prospective clinical trial. This study aims to investigate whether subcutaneous injection of m-Cresol at concentrations commonly used in clinical practice (0.1% and 0.25%) cause significantly more pain than a preservative-free control solution. In a randomized, double-blind crossover design, healthy volunteers will receive three separate injections in a belly fold. Participants will rate their pain every 5 seconds until it subsides. The findings will help determine if m-Cresol is a primary source of injection-site pain and could lead to the development of more comfortable drug formulations.

Primary objective- To assess the safety of nasal inoculation of healthy volunteers with B. pertussis with antibiotic therapy given to eradicate colonisation at 6 weeks after inoculation or at symptom onset, whichever occurs first Secondary objectives - To measure the rate of natural clearance of carriage of B. pertussis following nasal inoculation * To assess the kinetics of B. pertussis colonisation density following nasal inoculation * To describe the microevolution of B. pertussis and adaptation of the resident microbiome during B. pertussis carriage * To measure B. pertussis-specific antibody and cellular immunological responses in healthy volunteers during colonisation with B. pertussis - To identify biomarkers that correlate with natural clearance of B. pertussis carriage after induced B. pertussis colonisation * To detect transmission of B. pertussis to bedroom contacts of inoculated volunteers during prolonged asymptomatic colonisation

Drug-drug interaction study between Bemnifosbuvir/Ruzasvir (BEM/RZR) and Buprenorphine/Naloxone or Methadone

To Assess the Effect of Severe Hepatic or Renal Impairment on the Pharmacokinetics of Bemnifosbuvir/Ruzasvir After a Single Dose

This is a single-visit non-invasive study of healthy volunteer subjects. Brain activity will be measured with infra-red light sensors attached to a cap worn on the head, while both ears are gently stimulated with plastic filaments.

The goal of this clinical trial is to learn about the processes occurring in the kidneys while under heat stress in healthy volunteers. The main questions it aims to answer are: * How do the chemicals produced by the body change under conditions of higher versus lower heat stress? * What role does a specific area of the body's metabolism, known as NAD+ metabolism, play in the body's response to heat stress, and can this response be modified by taking vitamin B3?

This clinical investigation will assess the self-adhesive properties of two investigational devices compared to a test specimen reference.

The study consists of two parts: dose escalation and expansion. It includes five cohorts in the dose-escalation phase and two expansion cohorts based on pharmacokinetic data.

Gastric content is a key risk factor for aspiration during anesthesia. Although standard fasting times are recommended, various factors-including GLP-1 receptor agonists,-can delay gastric emptying. Gastric ultrasound enables real-time, non-invasive assessment of gastric volume and can help tailor perioperative management. The aim of this study explores the effects of different meal types and physical activity on gastric emptying in healthy individuals.

The goal of this clinical study is to evaluate safety of Xenon gas inhalation in healthy volunteers. This first phase safety clinical study is part of evaluation of the xenon gas inhalation as a therapy for neurodegenerative diseases, such as Alzheimer's disease. The investigators will administer xenon gas in low concentration to people via anesthetic machine, observe participants for sedation and any unexpected side effects, collect blood at each visit and measure the vital signs. There are four treatment groups in the study, which correspond with the duration of xenon gas treatment. Individual participation will last approximately 14 days over five visits: screening visit accompanied by the electrocardiogram, blood, and urine test; treatment visit for xenon gas inhalation treatment; and three follow up visits.

The study evaluates the effectiveness of a theoretical-practical training course for the ultrasound measurement of the optic nerve sheath diameter (ONSD), a non-invasive method used to estimate intracranial pressure (ICP). The optic nerve sheath is continuous with the subarachnoid space, which contains cerebrospinal fluid (CSF). An increase in ICP leads to an increase in CSF within the sheath, enlarging its diameter. ONSD measurement is typically performed by placing an ultrasound probe on the closed eyelid, allowing visualization of the optic nerve behind the eyeball. While the correlation between ONSD enlargement and elevated ICP is well-documented, there is variability in diagnostic cut-off values due to differences in measurement techniques, equipment, and operator experience. Previous studies have shown that even novice operators can achieve clinically acceptable accuracy after brief training. This study aims to assess whether medical students, nursing students, anesthesiology and intensive care residents, and intensive care nurses can learn to perform reliable ONSD measurements after a short training session. Methodology: The study will involve 40 participants unfamiliar with ONSD measurement: 10 medical students, 10 nursing students, 10 anesthesiology and intensive care residents, and 10 experienced intensive care nurses. The training will consist of a four-hour session, including a 30-minute lecture on ocular anatomy and ultrasound techniques, a real-time demonstration, and supervised hands-on practice with at least 20 measurements. Participants must pass a multiple-choice test with at least 70% correct answers to proceed to practical verification, where they will measure ONSD in five healthy volunteers. These measurements will be compared with those taken by an expert tutor. Measurement Technique: The ultrasound technique follows expert consensus guidelines, using a linear probe with a minimum frequency of 7.5 MHz. Volunteers will be positioned semi-seated at a 45° head elevation with closed eyelids. The ONSD measurement will be taken 3 mm behind the retina on the right eye. Care will be taken to avoid pressure on the eyeball, and safety parameters will be monitored to ensure compliance with FDA guidelines. The study aims to demonstrate that various healthcare professionals can achieve accurate and reliable ONSD measurements with proper training, enhancing the utility of this technique in diverse clinical settings.

This study aims to investigate the long-term impact of a non-pharmacological intervention including several activities (e.g., physical activity, choir, learning programs, horticulture, etc.) to prevent cognitive impairment in community-dwelling elderly individuals with aspects of frailty. The main questions it aims to answer are: * Does engaging in multiple activities, including music, slow the degeneration of perceptual and cognitive functions? * Is it possible to foster beneficial brain changes even during aging? * Can regularly attending social contexts reduce the risk of loneliness and provide fulfillment in later life? Researchers will compare participants involved in the multidomain intervention, including music, to another active group carrying out several activities but without music, and to a passive control group. Participants will: * Participate in the programs for 9 months; * Be tested three times (before and after the intervention, and at a 6-month follow-up); * Keep a weekly diary of the actual time spent in their activities.

A randomized, double-blind, placebo-controlled, parallel group, dose escalation study in healthy subjects to evaluate the safety, tolerability, pharmacokinetics and initial effectiveness of a novel intravenous CT contrast material (CZ10). This first-in-human clinical phase 1 trial will test the safety of escalating doses of CZ10 that has shown high safety and efficacy as a intravenous contrast agent in preclinical trials. The subjects for this study will be healthy adult volunteers, including obese but otherwise healthy subjects up to 450 lbs or the maximum allowable weight of the CT scanner, whichever is lighter. Subjects will be recruited and randomly assigned to cohort and test article. A total of 24 subjects will be evaluated with 18 subjects randomized to receive active drug and 6 subjects randomized to receive placebo control in a double blind manner. A total of three cohorts of 8 subjects will be enrolled. The first cohort subjects will receive a low dose, then if less than 2 subjects show severe adverse events, the second cohort will receive the expected clinical dose, then if less than 2 subjects show severe adverse events, the last cohort will receive a high dose of the intravenous test article. For each cohort, six subjects will be randomized to receive CZ10 and two to placebo. To increase subject safety, two initial subjects from each cohort will be randomized one to receive CZ10 and the other to receive placebo. If there are no serious adverse events through 3 days post dosing, then the remainder of the cohort will be enrolled. Subjects will be screened and enrolled up to 30 days prior to the day of test article dosing. Inclusion criteria are adult subjects willing to consent for the trial. Exclusion criteria are persons: (a) who are pregnant (as determined by a urine pregnancy test at the time of consent); (b) who have significant cardiovascular, respiratory, hepatic, gastrointestinal, hematological, neurological, psychiatric or other disease that may interfere with the objectives of the study and/or pose safety concerns; (c) Have evidence of moderate to severe renal insufficiency or renal failure (defined as an estimated glomerular filtration rate \<60 ml/minute); (d) who have an allergy to iodinated CT or other medical intravenous contrast material; (e) who are more than 450 pounds which would result in inability to be scanned on CT; or (f) have poor venous access such that an 18g venous cannula cannot be placed into the antecubital or other large superficial arm vein. Exclusion criteria also include women who are breastfeeding and women of childbearing age who are not using double protection birth control. Safety assessments will include monitoring of adverse events, vital signs (blood pressure, pulse rate, respiratory rate and oral temperature), clinical laboratory findings, 12-lead ECGs, subject reporting of symptoms, and physical examination findings. A physical examination will be performed at screening and on Day 2 and Day 7. A resting 12-lead ECG will be performed at screening, pre-dose and on Day 1 at 4 hours, Day 2, and Day 7. Vitals signs will be assessed at screening, at admission to the clinical research unit the day of dosing, then at 2, 4, and 7 hours after dosing, and on Day 2 and Day 7. Clinical laboratory tests (chemistry and hematology) will be performed at screening, pre-dose, at 7 hours after start of oral dosing, and Day 2 and 7 after dosing. A phone call interview to assess for symptoms will occur on day 15. In particular subjects will be monitored for possible allergic reaction, contrast material extravasation, and possible renal injury. If any adverse events are seen, the subject will be return to the clinical research unit for further assessment and possible treatment. Tentatively, the doses of CZ10 are expected to be 400, 800, and 1200 mg / kg of CZ10 but final doses will depend on preclinical and manufacturing data. The dose of test article will likely be limited by volume of material that can be bolus injected (maximum feasible dose). The placebo will be given at the same dose volume as the CZ10 drug product. At the conclusion of the study, the necessary safety data will be available to decide on whether and how to proceed with clinical phase 2 studies on patients with suspected or known vascular disease.