Ziln, Czech Republic

A Study of TAK-279 in Participants With Moderate-to-Severe Plaque Psoriasis

This study consists of 2 parts: Part A and Part B. Part A: Participants who did not participate in either parent study (TAK-279-3001 [NCT06088043] or TAK-279-3002 [NCT06108544]) may be enrolled and will be treated for up to 52 weeks. Participants who successfully complete Part A of the study are eligible to continue in Part B, but investigators must confirm their eligibility to continue in Part B. Part B: Participants who complete the treatment period of TAK-279-3001 (NCT06088043) or TAK-279-3002 (NCT06108544) parent studies or who complete Part A are eligible to enroll directly into open label extension treatment in Part B and will be treated for up to 156 weeks.

Measuring Upper Airway Cross Sectional Areas During Residual Neuromuscular Blockade and After Reserval

Introduction Postoperative residual neuromuscular can cause severe respiratory complications. One of these is pharyngeal dilator muscle weakness, which can lead to airway obstruction. One way to prevent this is to have objective neuromuscular monitors to track the degree of muscle relaxation and use the measurements to guide the the suspension of neuromuscular block. Monitoring the muscle relaxant effect is not a mandatory component of anaesthesia and is therefore often omitted in anaesthesiologists. In our study, the investigators investigated whether, at the end of surgery, only patients extubated at the end of surgery, based on clinical signs, have an airway diameter reduction and how this relates to the degree of residual muscle relaxation. Our single-centre, prospective study included 20 patients. The patients' narcosis by the anaesthetist, as is often done in routine anaesthesia work, is without monitoring neuromuscular block and on the basis of clinical signs deciding on extubation. Sample size calculation In a previous study, Eikermann and associates (Eikermann M, Vogt FM, Herbstreit F, Vahid-Dastgerdi M, Zenge MO, Ochterbeck C, de Greiff A, Peters J. The predisposition to inspiratory upper airway collapse during partial neuromuscular blockade. Am J Respir Crit Care Med. 2007;175(1):9-15.) using MRI technique described a minimal retroglossal diameter after a total neuromuscular recovery of 20.2±5.2 mm and a 20% decrease of this diameter at TOFR=0.8. the investigators hypothesised that in the present study, the decrease of the retroglossal cross-section area during inspiration will decrease by 30% in patients with residual neuromuscular block of any severity. Using and alpha of 0.05 and a power of 90%, 8 patients were calculated to be necessary to prove our hypothesis. In a previous study, it was found that in our working group the amount of residual neuromuscular block (as defined TOFR &lt;90%) during spontaneous recovery at the end of surgery approximates 45% of all cases (Nemes R, Fülesdi B, Pongrácz A, Asztalos L, Szabó- Maák Z, Lengyel S, Tassonyi E. Impact of reversal strategies on the incidence of postoperative residual paralysis after rocuronium relaxation without neuromuscular monitoring: A partially randomised placebo controlled trial. Eur J Anaesthesiol. 2017;34(9):609-616.). With respect to this, the investigators planned to include 18 patients. the investigators also calculated with eventual dropouts and finally included 20 patients. Procedure of the investigation During the operation, the anaesthetist will routinely administer anaesthesia, including the selection of muscle relaxant and the timing of extubation. The latter is based solely on clinical signs and the anaesthetist performing narcosis does not use a neuromuscular monitor. However, the patients are not left without monitoring of the effect of the muscle relaxant, as an independent anaesthesiologist performs continuous electromyographic neuromuscular monitoring of the anaesthetised patients, the actual values of which are not known to the anaesthetist. Medication of the patient, surgical procedure As part of the balanced anaesthesia routinely used at the institute, the patient is first premedicated with 7.5 mg midazolam 60 minutes before the onset of anaesthesia. A peripheral vein is secured in one arm of the patient and infusion with Ringer's lactate solution is started. The other arm is left completely free for the independent anaesthetist, on which neuromuscular monitoring is performed throughout the operation. Continuous monitoring of the patient's physiological parameters is ensured by the use of precordial ECG, pulse oximetry, blood pressure measurement, central body temperature measurement, end-expiratory oxygen and CO2 measurement throughout the duration of the operation. Induction of anaesthesia and maintenance of narcosis is achieved with total intravenous anaesthesia, propofol anaesthesia, TCI perfusion using the Schnider model. During induction, the propofol plasma concentration is set at 4-6 micrograms/ml. Before the administration of opioids and muscle relaxants, a control pharyngoscopy is performed, at which time the BIS index ranges between 60-70%. Patients are then asleep but spontaneous breathing is maintained. Once the recording is complete, the patient is given the type and dose of muscle relaxant chosen by the anaesthetist, fentanyl is administrated and the anethesist intubate the trachea. Subsequently, anaesthesia is deepened for the duration of the operation, with a BIS index of between 40-60%. The target concentration is then changed to 2.5-4 µg/ml to maintain narcosis. At the end of the operation, the non-monitoring anaesthetist performing the anaesthesia extubates the patient by observing the clinical signs, at which time the independent anaesthetist records the TOF value at the time of extubation. Fentanyl is antagonised while the patient is asleep. Pharyngoscopy is performed on the extubated patient. If necessary, i.e. when the TOF rate is below 90%, rescue medication is administered. Neuromuscular monitoring The anaesthetist did not monitor the patient, but the independent anaesthetist monitored the effects of the muscle relaxant throughout the operation. To do this, he uses a Tetragraph® electromyograph, which stimulates the ulnar nerve and detects the direct action potential of the adductor pollicis muscle. The application of the measuring instrument is facilitated by self-adhesive electrodes: the stimulating electrodes are placed on the volar surface of the wrist according to the course of the nerve mentioned above, and the sensing electrodes are placed towards the adductor pollicis muscle. The device is started with the patient already asleep, thus avoiding any discomfort due to stimulation. Once started, the device performs an autocalibration to determine the supramaximal excitation current to ensure muscle contraction. The electromyography uses the train of four -TOF stimulation pattern. Offline analysis of pharnygoscopy and airway areas During the examination of a patient, two pharyngoscopies are performed. The first one (called control pharnygoscopy) is performed under propofol but before the administration of opioid and muscle relaxant to ensure that the patient is breathing spontaneously. This is also to exclude the negative effect of opiate analgesia on the pharyngeal muscles. The second admission is performed after extubation. During the pharnygoscopy, a continuous chin lift, Escmarch-Heiberg manoeuvre, is used to guide the Ambu® aScope™ 4 Rhino Laryngo Slim rhino-laryngoscope down the nose to the vocal cord. The vocal fold was used as a landmark. From here, the camera was carefully retracted to locate the narrowest part of the pharynx, which corresponded to the retroglossal region. The found position is marked on the instrument with a marker, making it easier to find the same part of the pharynx for the second recording. During the pharyngoscopic examinations, moving images were also taken during the inhalation and exhalation phases, and these are analysed offline. Using the online available software Image J (Rasband WS, U.S. National Institutes of Health, Bethesda, Maryland, USA, https://imagej.net/ij/), the size of the airway areas is determined in pixels. From the resulting data set, the investigators can compare the data from control and end-of-operation pharyngoscopies and subsequently perform statistical calculations. Whenever possible, the investigators use analysis of variance (ANOVA) to estimate the parametric tests. Otherwise, the non-parametric Kruskal-Wallis test is used to compare each group. The significance level is defined as usual, p<0.05. Continuous variables are characterized by means and standard deviations. Rescue medication After pharyngoscopy, rescue medication is given if necessary, i.e. below 90% TOF, depending on the type of muscle relaxant used. If an aminosteroid muscle relaxant is used, the patient is given 2 mg/kg sugammadex, while if a benzylisoquinoline muscle relaxant is used, 0.05 mg/kg neostigmine and 0.015 mg/kg atropine are administrated to antagonise the drug effect.

A Phase III, Randomised Study of Adjuvant Dato-DXd in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Standard of Care, Following Complete Tumour Resection, in Participants With Stage I Adenocarcinoma NSCLC Who Are ctDNA-positive or Have High-risk Pathological Features

The primary objective of the study is to assess the efficacy and safety of adjuvant Dato-DXd in combination with rilvegostomig relative to SoC, after complete surgical resection (R0) in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive, as determined by the Sponsor-designated ctDNA assay, or have at least one high-risk pathological feature.

A Phase 3, Placebo-controlled, Double-blind Study Assessing Rocatinlimab in Prurigo Nodularis

Investigation of the Respiratory Profile of Patients With Obstructive Pulmonary Disease (ASTHMA, COPD)

Study Title: Assessment of the Relationship Between Inhalation Therapy Effectiveness and Breathing Profiles in Patients with Obstructive Pulmonary Diseases (OPTIPULM) The primary goal of this observational cross-sectional study is to analyze the relationship between patients' breathing characteristics and the effectiveness of their inhaled therapies. The study targets adult patients diagnosed with asthma or chronic obstructive pulmonary disease (COPD). Background and Rationale: Asthma and COPD are chronic obstructive airway diseases with increasing prevalence worldwide. Despite the availability of a wide range of inhaled medications and delivery devices, therapy is often suboptimal due to patient-specific factors such as improper inhalation technique or mismatch between inhaler resistance and the patient's inspiratory capacity. Emerging data suggest that aerosol deposition in the lungs-and therefore the efficacy of treatment-can be significantly influenced by the individual's breathing profile and the inhalation device used. However, this is rarely taken into account in routine clinical practice. Study Objectives: Primary Objective: To evaluate individual pulmonary function test (PFT) data and, based on this, to model and estimate drug deposition in the lungs using computer simulation for various inhaler-drug combinations. Secondary Objectives: To assess the inhalation techniques of patients. To recommend device optimization strategies based on flow-resistance matching. To identify which device (among commercially available options) is most likely to deliver the highest lung deposition for the individual patient.

Diagnostic Feasibility of 100 Hz Tetanic Stimulation

The aim of the present study is to investigate the applicability of 100 Hz tetanic stimulation with an electromyography (EMG) device. The aim is to determine whether fatigue develops with 100 Hz tetanic stimulation in anaesthetized, non-relaxed patients with normal or abnormal baseline electroneurographic (ENG) findings. Electric responses of the musculus digiti minimi elicited by supramaximal stimulation of the ulnar nerve at the carpal tunnel are monitored. Alpine Biomed ENG-EMG device with Keypoint software version 5.11 is used for the examinations. The exposed arm is fixed on the armboard, the skin is degreased and then the electrodes for monitoring are mounted lege artis. After the anesthesia has been induced, ENG of the ulnar nerve is examined. Based on the results of the ENG test, patients are divided into separate groups (normal or abnormal ENG). During the ENG test, the supramaximal current is determined. Afterwards, repetitive tetanic stimulation of the defined frequency (60 and 100 Hz) and duration (5 sec) is applied to the two test groups at the current according to the test plan. The clinical utilities of the study results are: - Determination of the "safety margin" of neuromuscular junction, which is not provided by routine monitoring. - To investigate how comorbid status (especially chronic conditions affecting peripheral nerves such as polyneuropathy) influences the feasibility of tetanic stimulation in the diagnostics of residual neuromuscular block and safety margin.

Investigation of Fixed Triple Inhaled Combination in Asthmatic Patients, in a Real-life Setting

Study design Multicentre, national, non-interventional, prospective study evaluating the effectiveness of Trimbow 172/5/9 μg pMDI on symptom scores in 6 months after switch from previous LABA-high dose ICS containing treatment in asthmatics. Dosage regimen and administration Name of the product: Trimbow 172 micrograms/5 micrograms/9 micrograms pressurised inhalation, solution (henceforth abbreviated as Trimbow 172/5/9 μg pMDI). Each delivered dose (the dose leaving the mouthpiece) contains 172 μg of beclometasone dipropionate, 5 μg of formoterol fumarate dihydrate and 9 μg of glycopyrronium (as 11 μg glycopyrronium bromide). Each metered dose (the dose leaving the valve) contains 200 μg of beclometasone dipropionate, 6 μg of formoterol fumarate dihydrate and 10 μg of glycopyrronium (as 12.5 μg glycopyrronium bromide). The recommended dose is two inhalations twice daily. The maximum dose is two inhalations twice daily. 1. Aim of the study (research objective) Primary objective: The main objective is to assess the effectiveness of BDP/FF/G 172/5/9 μg fixed triple combination in a real-world setting, with regards to improvements in symptom scores (ACT). 2. Test sample and method, recruitment principle No patient recruitment will be performed. Eligible patients will be enrolled during the participating physicians' regular asthma patient management and patients' written informed consent. Patient inclusion will take place among patients having severe asthma and attending pulmonology outpatient clinics (the chosen study sites are attached as annexes to the study protocol), strictly at the time of the patients' visit. The planned number of patients is 800. 3. Structure of the study In accordance with the requirements of non-interventional studies, the assignment of patients to Trimbow 172/5/9 μg pMDI therapy should be made independently of the study, and patients should only be considered for inclusion in the study after a prior therapeutic decision has been made by a pulmonologist. Patient enrolment can take place after the patient has been fully informed about the purpose of the study and all of its details, and the patient has read and signed the patient information leaflet and patient consent form, including any questions they may have. Once this has taken place, the data that would have been generated anyway during the outpatient examination of the patient in accordance with daily practice can be recorded. This is considered the first visit of the study (Visit 1). During this visit, the patient's main demographic data, information on comorbidities and concomitant medications, previous and current asthma therapies, asthma specific assessment (including ACT), exacerbation history, post-dose lung function values (if spirometry data is available), laboratory results (if a laboratory test is performed during the visit or was performed recently), results of other medical examinations (e.g., chest X-ray) if performed regardless of the study, maintenance and reliever inhaled & non-inhaled therapies (former and new) baseline quality of life based on the asthma quality of life (EQ-5D-5L) questionnaire, and adherence to therapy based on Test of Adherence to Inhalers® (TAI-12) questionnaire are recorded. Patients will then attend two additional visits 30 days and 6 months after enrolment as per routine clinical practice (Visits 2 and 3). During these visits, data will also be recorded, once again, according to routine clinical practice. Assessing the usage of rescue medications and patient adherence are also planned with the use of electronic health record system (EESZT)-verified prescription dispensations (optional for investigators). Visit 4 will be a long-term follow-up to assess the exploratory endpoint of exacerbations rates. If the patient's maintenance therapy changes during the study as decided by the treating pulmonologist, and the patient is no longer receiving Trimbow 172/5/9 μg pMDI, the patient will be automatically excluded from this NIS. The fact of the therapy modification and its exact date must be recorded on the "current medication" form in the eCRF (electronic Case Report Form) of the next visit. If the change in therapy is related to a suspected adverse reaction, it should be reported separately on the eCRF platform in accordance with section 9 of this protocol ('Collection, recording and reporting of medication safety data'). This NIS is open to all eligible patients according to the inclusion and exclusion criteria. Permitted concomitant treatments: allowed all medications according to local clinical practice (any non-inhalation therapy for asthma or other diseases) and reliever (short-acting bronchodilators) inhaled therapies for asthma. The data to be recorded will be detailed in the study data sheet that forms part of the protocol. The data is recorded in the eCRF (MrAgent - Medisol Development Ltd., see also at 10.1.) system, with consideration to the current professional and legal regulations. 4. Start and duration of the study The first patient enrolment will take place after receiving approval from the National Public Health Center (NPHC), based on a beneficial assessment of the Medical Research Council of Hungary. The study is planned to start on September 16, 2024. Accordingly, first patient first visit (FPFV) is also planned to take place in September, 2024. The launch of the participating centres is planned in two waves, in the autumn of 2024 and in the spring of 2025. Each centre will have 12 months to enrol patients. After the last visit of the last patient (LPLV), centres will have one month to collect all missing data / correct any data flagged as queries during monitoring. Thus, the LPLV will take place on Oct 31, 2026 (primary endpoint) and 30 April, 2027 (exploratory endpoint), respectively. The study is planned to be concluded on August 31, 2027. 5. Data to be recorded during the visits A total of 4 visits will be performed for the assessment of the primary and secondary endpoints during the study. The table below summarises the data collection to be carried out during the visits separately. The patient may be enrolled in the study and their data may only be recorded, if these data would also have been recorded in accordance with standard medical practice. - Visit 1: Time of enrolment - a normal visit, according to routine clinical practice. Informed consent and baseline patient characteristics will be collected. - Visit 2: 1 month after enrolment (± 2-3 workdays) - Visit 3: 6 months after enrolment (± 5-7 workdays) - Visit 4: 12 months after enrolment (± 10-15 days)

Comparison of Adductor Pollicis and Abductor Digiti Minimi Muscles (Thumb Vs. Fifth Digit) As Sites for Neuromuscular Monitoring with Electromyography

Introduction Residual neuromuscular blockade is a common occurrence in the post-anesthesia care unit (PACU) when neuromuscular blocking agents (NMBAs) have been used in the operating room. The only method of reliably detecting residual neuromuscular blockade is through the use of quantitative neuromuscular monitors. Unfortunately, several barriers exist that have prevented the widespread use of these devices. For instance, there is a paucity of quantitative neuromuscular monitors commercially available. Also, two modalities of quantitative monitoring, kinemyography and acceleromyography, rely on movement of the muscles of interest, a characteristic frequently compromised during patient positioning for surgical procedures in which the patient's arms are secured under surgical drapes (laparoscopic, bariatric, robotic, spine, and neurosurgical procedures) or in uncooperative awake patients in the PACU or intensive care unit (ICU). The aim of this investigation is to determine the different muscle sensitivities to NMBA and reversal agents by comparing responses at two different monitoring sites as measured with a new quantitative monitor. EMG measures electrical activity within the muscle following peripheral nerve stimulation and is unaffected by involuntary patient motion or by restricted muscle movements from surgical positioning. We plan to compare measurements obtained with two TetraGraph devices, one monitoring the adductor pollicis (thumb) muscle and the other monitoring adductor digiti minimi (5th digit) muscle, during onset, maintenance, and recovery of neuromuscular blockade. This will include monitoring every 20 sec for onset of blockade (defined as time from Train-of-Four ratio, TOFR=1.0 until Train-of-four count, TOFC=0) following rocuronium administration, during maintenance of neuromuscular block as required by surgical conditions, and following reversal administration until adequate recovery is documented (train-of-four ratio, TOFR ≥0.9). Medication of the patient, surgical procedure Upon entering the operating room, all patients underwent monitoring using electrocardiograms, noninvasive blood pressure measurements, and pulse oximetry. An intravenous catheter was inserted into either the forearm or the dorsal vein. Anesthesia was initiated with intravenous fentanyl (2.0 mg/kg) and propofol (1.5 to 2.5 mg/kg) and was maintained using sevoflurane (end-tidal concentration of 1.0 to 1.3%) in an air-oxygen mixture, with additional fentanyl given as needed. Before tracheal intubation, the patients were manually ventilated with 100% oxygen via facemask. Oxygen saturation was kept above 96%, and normocapnia was maintained. A forced air warming system (Bair Hugger, Arizant Healthcare Inc., Eden Prairie, Minnesota, USA) was used to keep the body temperature at or above 36°C. Intraoperative hypotension was treated with ephedrine, norepinephrine, or a fluid bolus, according to clinical indications. Ondansetron 4mg IV was routinely administered to prevent postoperative nausea and vomiting. Neuromuscular Management Before the induction of anesthesia, after appropriate skin cleaning, single-use surface TetraGraph electrodes were placed over the ulnar nerve and thumb to assess the adductor pollicis response on one hand, and over the ulnar nerve and fifth digit to assess the abductor digiti minimi response on the other hand. Following the induction of anesthesia, train-of-four (TOF) stimulation was applied to both muscle groups at a frequency of 2 Hz for 1.5 seconds every 15 seconds, after the automated calibration of supramaximal current and responses. Once stable baseline TOF responses were established, all patients received 0.6 mg/kg of rocuronium intravenously. Measurements were taken every five minutes during the intraoperative period until the administration of sugammadex. After that, we monitored the spontaneous recovery of the rocuronium-induced neuromuscular block until three consecutive TOF counts of 2 (TOFC2) were observed at both monitoring sites. Additional doses of rocuronium (0.1-0.2 mg/kg) were administered as necessary to maintain a Train of Four (TOF) count of ≤2. At the end of the surgery, sugammadex was given at a dose of 2 mg/kg. After administering sugammadex, measurements were taken every 20 seconds until the patient was extubated. Following the measurements obtained with both devices at the specified intervals, and once the TOF ratio exceeded 0.9, the devices were disconnected, and the patients continued along the standard recovery pathway. Rescue medication After pharyngoscopy, rescue medication is given if necessary, i.e. below 90% TOF, depending on the type of muscle relaxant used. If an aminosteroid muscle relaxant is used, the patient is given 2 mg/kg sugammadex, while if a benzylisoquinoline muscle relaxant is used, 0.05 mg/kg neostigmine and 0.015 mg/kg atropine are administrated to antagonise the drug effect.

A Study in Patients With Moderate to Severe Plaque Psoriasis to Evaluate the Efficacy and Safety of ESK-001

LIDRISE Study: A Phase 3 Study on the Efficacy and Safety of STN1013800 (Oxymetazoline HCl 0.1% Eye Drops, Single Dose) in the Treatment of Acquired Blepharoptosis.

This is a randomised, double-masked, placebo-controlled Phase 3 study of the safety and efficacy of STN1013800 in the treatment of acquired blepharoptosis. Subjects diagnosed with acquired blepharoptosis who meet eligibility criteria at Visit 1 (Screening) will return within 8 days for Visit 2 (Baseline, Day 1). At Visit 2 (Baseline, Day 1) they will be randomised to receive double-masked treatment for 6 weeks, with study visits completed at Week 2 (Day 14) and Week 6 (Day 42), and a post-treatment visit completed 2 weeks (± 3 days) after last study drug administration. Approximately 234 adult subjects with blepharoptosis who meet all the eligibility criteria will be randomised in a 1:1 ratio to receive: - STN1013800 BID - Placebo BID Note that: - On study visits Day 1 and Day 42, the AM dose is administered at 08:00 (at site) and the PM dose is administered at 16:00 (self-administered at home) - On study visit Day 14, the AM dose is administered at 06:00 (self-administered at home), the PM dose is administered at 14:00 (at site)