Abstract Background Risankizumab (RZB) is a high-affinity humanized IgG1 monoclonal antibody that selectively binds to the p19 subunit of human IL-23 cytokine, thereby inhibiting its interaction with receptor.1 RZB was intentionally designed modifications could contribute prolonged half-life, low immunogenicity, and increased stability bioavailability.1 The objective this post-hoc analysis characterise pharmacokinetic (PK) pharmacodynamic (PD) effects following withdrawal in patients...

Integrating digital health technologies (DHTs), such as wearable sensors and mobile device applications, into model-informed drug development offers unprecedented opportunities by collecting continuous patient data remotely objectively assessing behavior. This study aims to showcase the benefits challenges of integrating biomarkers enhance evaluation efficacy safety, using a case on sleep parameter monitoring in Phase 2 clinical trial. In this study, was collected from 35...

Data from phase IIb/III and III studies were used to characterize the population pharmacokinetics of risankizumab its exposure-response relationships for efficacy safety in ulcerative colitis (UC) patients. A two-compartment model with first-order absorption elimination accurately described pharmacokinetics. Although certain covariates, namely, body weight, serum albumin, fecal calprotectin, sex, corticosteroid use, advanced therapy inadequate response, pancolitis, statistically correlated...

Exposure–response analyses of upadacitinib (UPA) key efficacy and safety end points (3,685 4,577 subjects for safety, respectively) using data from phase II III rheumatoid arthritis (RA) studies were conducted to support benefit–risk assessment. Percentage achieving American College Rheumatology (ACR)20/50/70, disease activity score 28 (C‐reactive protein) (DAS28‐CRP) ≤ 3.2, DAS28‐CRP < 2.6 increased with increasing UPA plasma exposures. With the small number observed events, no clear...

Elagolix is a novel oral gonadotropin releasing hormone receptor antagonist, that can suppress estradiol in dose-dependent manner. It indicated for management of moderate-to-severe pain associated with endometriosis. A population exposure-response model describing the relationship between elagolix exposure and changes bone mineral density (BMD) was developed using data from four phase III studies premenopausal women endometriosis-associated pain. pharmacokinetic exposure-dependent BMD were...

Aim Elagolix, a gonadotropin‐releasing hormone receptor antagonist, was recently approved for heavy menstrual bleeding associated with uterine fibroids (UF, Oriahnn) at dose of 300 mg twice daily (BID) in combination add‐back therapy (oestradiol 1 mg/norethindrone acetate 0.5 [E2/NETA] once daily) 24 months use. The limited duration treatment is related to elagolix dose‐ and duration‐dependent decrease oestrogen that mechanistically linked changes bone mineral density (BMD). work herein...

Abstract Decline of bone mineral density (BMD) during menopause is related to increased risk fractures in postmenopausal women, however, this relationship premenopausal women has not been established. To quantify relationship, real‐world data (RWD) from the National Health and Nutrition Examination Survey (NHANES), longitudinal elagolix phase III clinical trials were modeled across a wide age range, covariates evaluated. The natural changes femoral neck BMD (FN‐BMD) well‐described by...

Abstract Elagolix is a novel, oral gonadotropin‐releasing hormone receptor antagonist indicated for the management of moderate to severe pain associated with endometriosis and heavy menstrual bleeding uterine fibroids. Consistent its mechanism action, elagolix exhibited dose‐dependent suppression estradiol (E2) in clinical studies. A dose‐response model that describes relationship between dosages average E2 levels was combined previously published quantitative systems pharmacology (QSP)...

Selection of a personalized dose for an individual patient can be informed by the patient's preferences, translated as weights on each clinically relevant safety and efficacy drug attributes, based results from brief preference elicitation questionnaire. In this analysis, weighted attributes were simulated to represent various endometriosis profiles. Exposure-response simulations performed elagolix, approved management moderate severe pain associated with endometriosis, across range plasma...

Elagolix is an orally active, gonadotropin-releasing hormone receptor antagonist approved for the management of endometriosis-associated pain and heavy menstrual bleeding associated with uterine fibroids. population pharmacokinetics factors affecting elagolix exposure in healthy women endometriosis have been reported previously. The purpose this study was to extend model additional modifications incorporate data from phase III studies hormonal add-back therapy Data 13 clinical (a total 2168...

Abstract Background Risankizumab (RZB) has been evaluated in subjects with moderately to severely active ulcerative colitis (UC) the INSPIRE and COMMAND trials. Population pharmacokinetic (PPK) exposure-response (ER) analyses were conducted at end of Phase 2b following 3 characterize RZB PK its relationship clinical efficacy safety support induction dose selection, final recommendations for maintenance treatment. Methods PPK UC used a previously developed model Crohn’s disease additional...

Elagolix is an oral gonadotropin‐releasing hormone antagonist approved by the US Food and Drug Administration (FDA) for management of moderate‐to‐severe pain associated with endometriosis in combination estradiol/norethindrone acetate heavy menstrual bleeding uterine leiomyomas (fibroids) premenopausal women. The objective this work was to characterize relationships between elagolix exposures clinical efficacy response rates dysmenorrhea (DYS) nonmenstrual pelvic (NMPP) women enrolled...

Dissolution specifications are often essential in assuring the quality and consistency of therapeutic benefits drug lots released to market as vitro dissolution is considered be a surrogate for bioavailability. Despite importance demonstrating clinical relevance specifications, it challenging achieve this goal. In case study, modeling simulation approach was utilized support upadacitinib extended-release tablets. A level vivo correlation developed predicting plasma exposures formulations...

<h3>Background</h3> Upadacitinib (UPA), an oral selective JAK1 inhibitor, demonstrated favorable efficacy and acceptable safety in two Phase 2 five 3 global studies subjects with moderately to severely active rheumatoid arthritis (RA). <h3>Objectives</h3> To characterize relationships between UPA plasma exposures different endpoints using data from RA studies. <h3>Methods</h3> Analyses were conducted 3685 (for efficacy) 4577 safety) enrolled the Relationships concentrations selected...