scholarly journals Pharmacokinetic/pharmacodynamic modeling for dose selection for the first‐in‐human trial of the activated Factor XII inhibitor garadacimab (CSL312)

2021 ◽  
Author(s):  
Dipti Pawaskar ◽  
Xi Chen ◽  
Fiona Glassman ◽  
Frauke May ◽  
Anthony Roberts ◽  
...  
Keyword(s):  
Pharmacodynamic Modeling ◽  
Factor Xii ◽  
Dose Selection ◽  
Human Trial ◽  
Selection For

Population Pharmacokinetic and Pharmacodynamic Modeling of AZD4901 and Simulation to Support Dose Selection for the Phase 2a Study

2016 ◽  
Vol 56 (8) ◽  
pp. 999-1008 ◽  
Author(s):  
Hongmei Xu ◽  
Jianguo Li ◽  
Lorraine Webber ◽  
Rahul Kakkar ◽  
Yingxue Chen ◽  
...  
Keyword(s):  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Dose Selection ◽  
Selection For

scholarly journals Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529

2016 ◽  
Vol 60 (5) ◽  
pp. 2782-2789 ◽  
Author(s):  
Ishani Landry ◽  
Li Zhu ◽  
Malaz Abu Tarif ◽  
Matthew Hruska ◽  
Brian M. Sadler ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Clinical Investigation ◽  
Central Compartment ◽  
Pharmacodynamic Modeling ◽  
Dose Selection ◽  
Phase 3 ◽  
Viral Attachment ◽  
First Order ◽  
Selection For ◽  
Hiv 1

ABSTRACTBMS-663068 is an oral prodrug of the HIV-1 attachment inhibitor BMS-626529, which prevents viral attachment to host CD4+T cells by binding to HIV-1 gp120. To guide dose selection for the phase 3 program, pharmacokinetic/pharmacodynamic modeling was performed using data from two phase 2 studies with HIV-1-infected subjects (n= 244). BMS-626529 population pharmacokinetics were described by a two-compartment model with first-order elimination from the central compartment, zero-order release of prodrug from the extended-release formulation into a hypothetical absorption compartment, and first-order absorption into the central compartment. The covariates of BMS-663068 formulation type, lean body mass, baseline CD8+T-cell percentage, and ritonavir coadministration were found to be significant contributors to intersubject variability. Exposure-response analyses showed a relationship between the loge-transformed concentration at the end of a dosing interval (Ctau) normalized for the protein binding-adjusted BMS-626529 half-maximal (50%) inhibitory concentration (PBAIC50) and the change in the HIV-1 RNA level from the baseline level after 7 days of BMS-663068 monotherapy. The probability of achieving a decline in HIV-1 RNA level of >0.5 or >1.0 log10copies/ml as a function of the loge-transformed PBAIC50-adjustedCtauafter 7 days of monotherapy was 99 to 100% and 57 to 73%, respectively, for proposed BMS-663068 doses of 400 mg twice daily (BID), 600 mg BID (not studied in the phase 2b study), 800 mg BID, 600 mg once daily (QD), and 1,200 mg QD. On the basis of a slight advantage in efficacy of BID dosing over QD dosing, similar responses for the 600- and 800-mg BID doses, and prior clinical observations, BMS-663068 at 600 mg BID was predicted to have the optimal benefit-risk profile and selected for further clinical investigation. (The phase 2a proof-of-concept study AI438006 and the phase 2b study AI438011 are registered at ClinicalTrials.gov under numbers NCT01009814 and NCT01384734, respectively.)

Variation in Severity Assessment and Initial Mesalamine Dose Selection for Ulcerative Colitis in Community Practice

2006 ◽  
Vol 40 (7) ◽  
pp. 587-591 ◽  
Author(s):  
Bruce E. Sands ◽  
Karl M. Kilgore ◽  
Richard S. Bloomfeld ◽  
William J. Sandborn
Keyword(s):  
Ulcerative Colitis ◽  
Severity Assessment ◽  
Community Practice ◽  
Dose Selection ◽  
Selection For

scholarly journals Pharmacokinetic-Pharmacodynamic (PK-PD) Target Attainment (TA) Analyses Supporting Lefamulin Dose Selection for the Treatment of Patients With Community-Acquired Bacterial Pneumonia (CABP)

2015 ◽  
Vol 2 (suppl_1) ◽  
Author(s):  
Sujata M. Bhavnani ◽  
Paul G. Ambrose ◽  
Wolfgang W. Wicha ◽  
Zrinka Ivezic-Schoenfeld ◽  
William T. Prince ◽  
...  
Keyword(s):  
Bacterial Pneumonia ◽  
Target Attainment ◽  
Dose Selection ◽  
Selection For
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