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Idiopathic pulmonary fibrosis is characterized by rapid loss of vital capacity, disability, and death. There are no effective treatments. Although this study failed to meets its primary end point, the data show therapeutic efficacy at a cost of substantial GI toxicity. Idiopathic pulmonary fibrosis is a debilitating disease characterized by destruction of the gas-exchanging regions of the lung. 1 Its pathogenesis is thought to involve aberrant wound healing mediated by multiple signaling pathways, resulting in progressive lung injury and scarring. 1 Symptoms, including cough and dyspnea, limit physical activity and reduce the patient's quality of life and independence. 2 The course of the disease is difficult to predict, but it generally involves progressive deterioration, with a median survival time of 2.5 to 3.5 years after diagnosis. 3 Unpredictable acute exacerbations occur in some patients and are often fatal. 3 , 4 BIBF 1120 is a potent intracellular . . .

Clinical research increasingly recognizes the role and value of patient-centric data incorporation in trial design, aiming for more relevant, feasible, and engaging studies for participating patients. Despite recognition, research on analytical models regarding qualitative patient data analysis has been insufficient. This pilot study aims to explore and demonstrate the analytical framework of the \"patient feasibility\" concept-a novel approach for integrating patient-centric data into clinical trial design using psychometric latent class analysis (LCA) and interval response theory (IRT) models. A qualitative survey was designed to capture the diverse experiences and attitudes of patients in an oncological indication. Results were subjected to content analysis and categorization as a preparatory phase of the study. The analytical phase further employed LCA and hybrid IRT models to discern distinct patient subgroups and characteristics related to patient feasibility. LCA identified three latent classes each with distinct characteristics pertaining to a latent trait defined as patient feasibility. Covariate analyses further highlighted subgroup behaviors. In addition, IRT analyses using the two-parameter logistic model, generalized partial credit model, and nominal response model highlighted further distinct characteristics of the studied group. The results provided insights into perceived treatment challenges, logistic challenges, and limiting factors regarding the standard of care therapy and clinical trial attitudes.

ABSTRACT Purpose To develop a semi-mechanistic population pharmacokinetic/pharmacodynamic (PKPD) model for the selective bradycardic agent cilobradine describing simultaneously the heart rate (HR) measured at rest and just after the end of exercise sharing the same set of PKPD parameters. Methods Healthy subjects received cilobradine orally once daily over 2 weeks at 0.25–5 mg doses or placebo. Plasma drug concentrations and HR were measured at rest and following 3 min of exercise over the entire study period. PK and HR data were analyzed using the population approach with NONMEM VII. Results Plasma disposition of cilobradine was described with a three compartment model. Cilobradine showed dose proportional and time independent pharmacokinetics. HR response was drug concentration dependent and appeared with a significant delay with respect to PK profiles, a phenomenon modeled using two transit compartments. Perturbation in HR at rest as a consequence of exercise was described assuming that physiological processes controlling cardiac frequency were constantly increased over the period of exercise only. Conclusions The selected model provides a useful modeling tool for cases where the PD response measured is the result of a temporal experimental induced perturbation.