A study to evaluate the processing by the body and safety of pralsetinib in participants with hepatic impairment compared to healthy participants

2021 ◽  
Author(s):  
Clinical Trials
Keyword(s):  
Hepatic Impairment ◽  
The Body ◽  
Healthy Participants

scholarly journals Single-dose pharmacokinetics of BMS-986177/JNJ-70033093 in participants with mild or moderate hepatic impairment compared to healthy participants

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Perera ◽  
G Abelian ◽  
D Li ◽  
Z Wang ◽  
L Zhang ◽  
...  
Keyword(s):  
Single Dose ◽  
Hepatic Impairment ◽  
Hepatic Function ◽  
Moderate Hepatic Impairment ◽  
Funding Source ◽  
Antithrombotic Agents ◽  
Normal Hepatic Function ◽  
Pugh Class ◽  
Healthy Participants ◽  
Mild Hepatic Impairment

Abstract Background According to the scientific evidence accumulated to date (ie, genetic, epidemiological, preclinical, clinical), the modulation of Factor XI (FXI) function may provide a novel mechanism for systemic anticoagulation without increasing the risk of clinically significant bleeding in a variety of conditions predisposing patients to a high risk of thrombotic or bleeding events. BMS-986177/JNJ-70033093 (BMS-177/JNJ-3093) is a small molecule that inhibits the active form of FXI (FXIa) with high affinity and selectivity. Depending on the indication, BMS-177/JNJ-3093 may provide benefit to patients as add-on or potentially replacement therapy to the current standard of care antithrombotic agents. Patients with hepatic impairment may have an increased risk of bleeding when using existing antithrombotic agents and therefore may benefit from drugs with an improved safety profile. Purpose To assess the effect of mild or moderate hepatic impairment on the pharmacokinetic (PK) properties of BMS-177/JNJ-3093. Methods This was a multicenter, open-label, non-randomized, single-dose study. A single 60-mg oral dose of BMS-177/JNJ-3093 was administered to 9 participants with mild hepatic impairment (Child-Pugh class A), 8 participants with moderate hepatic impairment (Child-Pugh class B), and 9 healthy participants with normal hepatic function. Healthy participants were matched to participants with hepatic impairment in each Child-Pugh class with regard to body weight. To assess the effects of hepatic impairment on BMS-177/JNJ-3093 PK, an analysis of variance was performed on the natural log-transformed Cmax, AUC(INF), and AUC(0-T) with hepatic function group as a fixed effect. Results BMS-177/JNJ-3093 was well tolerated when administered as an oral dose of 60 mg in participants with mild or moderate hepatic impairment and healthy participants with normal hepatic function. There were no deaths, serious adverse events (AEs), severe AEs, bleeding AEs, or discontinuations due to an AE reported during the study. The geometric mean ratios (GMRs) (90% CI) comparing mild hepatic impairment to normal hepatic function were 1.180 (0.735, 1.895) and 1.168 (0.725, 1.882) for total BMS-177/JNJ-3093 maximum concentration (Cmax) and area under the curve from time 0 to infinity (AUC(INF)), respectively. The GMRs (90% CI) comparing moderate hepatic impairment to normal hepatic function were 1.140 (0.699, 1.857) and 0.996 (0.609, 1.628) for total BMS-177/JNJ-3093 Cmax and AUC(INF), respectively. Overall, levels of activated partial thromboplastin time (aPTT) increased in an exposure-related manner following single oral doses of 60 mg BMS-177/JNJ-3093 in all groups. Conclusion BMS-177/JNJ-3093 was well tolerated in the normal healthy participants and those with mild or moderate hepatic impairment. The observed changes indicate that a dose adjustment in these populations may not be necessary. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This work was sponsored by Bristol-Myers Squibb and Janssen Research & Development, LLC

scholarly journals Reliability and concurrent validity of the iPhone® Compass application to measure thoracic rotation range of motion (ROM) in healthy participants

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4431 ◽  
Author(s):  
James Furness ◽  
Ben Schram ◽  
Alistair J. Cox ◽  
Sarah L. Anderson ◽  
Justin Keogh
Keyword(s):  
Correlation Coefficient ◽  
Thoracic Spine ◽  
Concurrent Validity ◽  
Measurement Techniques ◽  
Intraclass Correlation ◽  
Smart Phone ◽  
The Body ◽  
Rater Reliability ◽  
Healthy Participants

Background Several water-based sports (swimming, surfing and stand up paddle boarding) require adequate thoracic mobility (specifically rotation) in order to perform the appropriate activity requirements. The measurement of thoracic spine rotation is problematic for clinicians due to a lack of convenient and reliable measurement techniques. More recently, smartphones have been used to quantify movement in various joints in the body; however, there appears to be a paucity of research using smartphones to assess thoracic spine movement. Therefore, the aim of this study is to determine the reliability (intra and inter rater) and validity of the iPhone® app (Compass) when assessing thoracic spine rotation ROM in healthy individuals. Methods A total of thirty participants were recruited for this study. Thoracic spine rotation ROM was measured using both the current clinical gold standard, a universal goniometer (UG) and the Smart Phone Compass app. Intra-rater and inter-rater reliability was determined with a Intraclass Correlation Coefficient (ICC) and associated 95% confidence intervals (CI). Validation of the Compass app in comparison to the UG was measured using Pearson’s correlation coefficient and levels of agreement were identified with Bland–Altman plots and 95% limits of agreement. Results Both the UG and Compass app measurements both had excellent reproducibility for intra-rater (ICC 0.94–0.98) and inter-rater reliability (ICC 0.72–0.89). However, the Compass app measurements had higher intra-rater reliability (ICC = 0.96 − 0.98; 95% CI [0.93–0.99]; vs. ICC = 0.94 − 0.98; 95% CI [0.88–0.99]) and inter-rater reliability (ICC = 0.87 − 0.89; 95% CI [0.74–0.95] vs. ICC = 0.72 − 0.82; 95% CI [0.21–0.94]). A strong and significant correlation was found between the UG and the Compass app, demonstrating good concurrent validity (r = 0.835, p < 0.001). Levels of agreement between the two devices were 24.8° (LoA –9.5°, +15.3°). The UG was found to consistently measure higher values than the compass app (mean difference 2.8°, P < 0.001). Conclusion This study reveals that the iPhone® app (Compass) is a reliable tool for measuring thoracic spine rotation which produces greater reproducibility of measurements both within and between raters than a UG. As a significant positive correlation exists between the Compass app and UG, this supports the use of either device in clinical practice as a reliable and valid tool to measure thoracic rotation. Considering the levels of agreement are clinically unacceptable, the devices should not be used interchangeably for initial and follow up measurements.

scholarly journals Subjective Hunger, Gastric Upset, and Sleepiness in Response to Altered Meal Timing during Simulated Shiftwork

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1352 ◽  
Author(s):  
Charlotte C Gupta ◽  
Stephanie Centofanti ◽  
Jillian Dorrian ◽  
Alison M Coates ◽  
Jacqueline M Stepien ◽  
...  
Keyword(s):  
Energy Intake ◽  
Mixed Model ◽  
The Body ◽  
Subjective Responses ◽  
Male Age ◽  
Macronutrient Content ◽  
Meal Timing ◽  
Desire To Eat ◽  
The Impact ◽  
Healthy Participants

Shiftworkers report eating during the night when the body is primed to sleep. This study investigated the impact of altering food timing on subjective responses. Healthy participants (n = 44, 26 male, age Mean ± SD = 25.0 ± 2.9 years, BMI = 23.82 ± 2.59kg/m2) participated in a 7-day simulated shiftwork protocol. Participants were randomly allocated to one of three eating conditions. At 00:30, participants consumed a meal comprising 30% of 24 h energy intake (Meal condition; n = 14, 8 males), a snack comprising 10% of 24 h energy intake (Snack condition; n = 14; 8 males) or did not eat during the night (No Eating condition; n = 16, 10 males). Total 24 h individual energy intake and macronutrient content was constant across conditions. During the night, participants reported hunger, gut reaction, and sleepiness levels at 21:00, 23:30, 2:30, and 5:00. Mixed model analyses revealed that the snack condition reported significantly more hunger than the meal group (p < 0.001) with the no eating at night group reporting the greatest hunger (p < 0.001). There was no difference in desire to eat between meal and snack groups. Participants reported less sleepiness after the snack compared to after the meal (p < 0.001) or when not eating during the night (p < 0.001). Gastric upset did not differ between conditions. A snack during the nightshift could alleviate hunger during the nightshift without causing fullness or increased sleepiness.

Illusion as a Research Tool for Inter-analyzer Interaction (Iai) Characteristics in a Psychiatric Clinic

2017 ◽  
Vol 41 (S1) ◽  
pp. S634-S634
Author(s):  
M. Kovyazina ◽  
K. Fomina ◽  
N. Varako
Keyword(s):  
Brain Activity ◽  
Cognitive Activity ◽  
Biological Significance ◽  
The Body ◽  
Psychiatric Clinic ◽  
Research Subjects ◽  
Competing Interest ◽  
Significant Patterns ◽  
Healthy Participants ◽  
Qualitative And Quantitative Characteristics

IntroductionIAI does not only play a functional role but also has qualitative and quantitative characteristics. Biological significance of IAI consists in mobilization of some sensory functions and demobilization of others as a response to a stimulus signaling changes in the environment. This constitutes one of the manifestations of body's preparatory reactions for action in the forthcoming situation. It has been established that in patients with psychic pathology such preparation of the body systems is affected, which may manifest through changes in illusion frequency.ObjectivesTo apply Charpentier illusion to research IAI characteristics with the purpose of further detection of abnormalities in the sphere of intermodal interaction.MethodsOne of the IAI research methods, is illusion research, e.g. Charpentier illusion, since it is based on interaction between visual and proprioceptive analyzers. Changes in preparatory reaction in subjects with psychic pathology is characterized by decline in illusion frequency, patients in these conditions should evaluate stimuli more correctly than healthy participants. Pre-experimental research design included two subjects: with white matter pathology (patient G., male, 27, full agenesis of CC, based on MRI results) and with IDD (subject A., male, 30).ResultsResearch subjects demonstrated absence of illusions, which is indicative of functional weakness of IAI, which results in inconsistency of sensory systems and meaningless perception. IAI plays an important role in formation of human psyche by enabling the development of significant patterns underlying human cognitive activity.ConclusionIllusion research is relevant for clinical psychological diagnosis of diseases associated with integrative brain activity disorders.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals When Me Is Mine: An Embodied Origin of Psychological Ownership?

2020 ◽  
Author(s):  
Aurora De Bortoli Vizioli ◽  
Anna M. Borghi ◽  
Luca Tummolini
Keyword(s):  
The Body ◽  
Psychological Ownership ◽  
Matching Task ◽  
Cognitive Mechanisms ◽  
Rubber Hand ◽  
Indirect Measure ◽  
Long Time ◽  
Perceptual Matching ◽  
Cascade Effects ◽  
Healthy Participants

Neurological evidence has shown that brain damages canselectively impair the ability to discriminate between objectsbelonging to others and those that we feel are our own. Despite the ubiquity and relevance of this sense of object ownership for our life, the underlying cognitive mechanisms are still poorly understood. Here we ask whether psychological ownership of an object can be based on its incorporation in one’s body image. To explore this possibility with healthy participants, we employed a modified version of the rubber-hand illusion in which both the participant and the rubber hand wore a ring. We used the self-prioritization effect in a perceptual matching task as an indirect measure of the sense of (dis)ownership over objects. Results indicate that undermining the bodily self has cascade effects on the representation of owned objects, at least for those associated with the body for a long time.

scholarly journals Anterior insular cortex plays a critical role in interoceptive attention

2018 ◽  
Author(s):  
Xingchao Wang ◽  
Qiong Wu ◽  
Laura Egan ◽  
Xiaosi Gu ◽  
Pinan Liu ◽  
...  
Keyword(s):  
Critical Role ◽  
Insular Cortex ◽  
The Body ◽  
Physiological Signals ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Discrimination Accuracy ◽  
Anterior Insular Cortex ◽  
Interoceptive Accuracy ◽  
Healthy Participants

AbstractAlthough accumulating evidence indicates that the anterior insular cortex (AIC) mediates interoceptive attention, which refers the attention towards physiological signals arising from the body, the necessity of the AIC in this process has not been demonstrated. Using a novel task that directs attention toward breathing rhythm, we assessed the involvement of the AIC in interoceptive attention in healthy participants using functional magnetic resonance imaging and examined the necessity of the AIC in interoceptive attention in patients with AIC lesions. We found that interoceptive attention was associated with greater AIC activation, as well as enhanced coupling between the AIC and somatosensory area along with reduced coupling between AIC and visual sensory areas. AIC activation and connectivity were predictive of individual differences in interoceptive accuracy. Importantly, AIC lesion patients showed disrupted interoceptive discrimination accuracy and sensitivity. Together, these results provide compelling evidence that AIC plays a critical role in interoceptive attention.

Sign in / Sign up

Export Citation Format

Share Document