scholarly journals Population Exposure-Response Modeling Supported Selection of Naloxegol Doses in Phase III Studies in Patients With Opioid-Induced Constipation

2017 ◽  
Vol 6 (10) ◽  
pp. 705-711 ◽  
Author(s):  
Nidal Al-Huniti ◽  
Hongmei Xu ◽  
Diansong Zhou ◽  
Sergey Aksenov ◽  
Robert Fox ◽  
...  
Keyword(s):  
Phase Iii ◽  
Population Exposure ◽  
Exposure Response ◽  
Response Modeling ◽  
Phase Iii Studies ◽  
Selection Of

scholarly journals Dose/Exposure-Response Modeling to Support Dosing Recommendation for Phase III Development of Baricitinib in Patients with Rheumatoid Arthritis

2017 ◽  
Vol 6 (12) ◽  
pp. 804-813 ◽  
Author(s):  
Xin Zhang ◽  
Laiyi Chua ◽  
Charles Ernest ◽  
William Macias ◽  
Terence Rooney ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Phase Iii ◽  
Exposure Response ◽  
Response Modeling

Alectinib exposure-response (ER) in ALK-inhibitor naïve ALK-positive NSCLC patients: Pooled analysis across phase III studies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20575-e20575
Author(s):  
Kevin Smart ◽  
Joy C Hsu ◽  
Felix Jaminion ◽  
Elena Guerini ◽  
Alice Tsang Shaw ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Alk Inhibitor ◽  
Exposure Response ◽  
Alk Positive ◽  
Nsclc Patients ◽  
Phase Iii Studies

e20575 Background: Alectinib superiority to crizotinib has been demonstrated in ALK-inhibitor naïve ALK-positive NSCLC patients (pts) in Phase III studies conducted in Japanese (J-ALEX; JapicCTI-132316) pts receiving alectinib 300 mg BID and global (ALEX; NCT02075840) and Asian (ALESIA; NCT02838420) pts receiving alectinib 600mg BID. ER analyses are undertaken to confirm the appropriate alectinib dosing regimen for the global population. Methods: A previous population PK analysis (Hsu et al, ASCO 2016) assessed PK of alectinib and major metabolite, M4, to identify factors influencing PK variability. ER analyses across the 3 Phase III studies investigated the relationship between alectinib and progression-free survival (PFS) by a Cox proportional hazards (CPH) analysis. PK simulations for alectinib 300 mg and 600 mg BID doses were conducted to determine the proportion of pts falling above and below an identified optimal PK threshold for PFS. ER for key safety events were investigated for alectinib 600 mg BID using logistic regression. Results: Alectinib PK is influenced only by body weight and not by race/ethnicity. CPH analysis demonstrated a statistically significant relationship between alectinib exposure and PFS across the 3 Phase III studies, with an improved PFS above an identified optimal PK threshold (Table). PK simulations indicate 49% and 7% of global alectinib treated patients would fall below the optimal PK threshold for 300 and 600mg BID, respectively. Alectinib 600mg BID ensures a distribution of exposures that maximize the PFS benefit while lower alectinib doses/exposures could result in reduced efficacy. Baseline tumor size (BSIZ) was shown to negatively impact PFS with larger BSIZ seen in global pts. No significant exposure-safety relationships were identified for alectinib 600mg BID. Conclusions: Alectinib 600mg BID is the most appropriate dose in the global ALK-inhibitor naïve population. Clinical trial information: NCT02075840; JapicCTI-132316; NCT02838420. [Table: see text]

scholarly journals Population Exposure‐Response Modeling of Naloxegol in Patients With Noncancer‐Related Pain and Opioid‐Induced Constipation

2016 ◽  
Vol 5 (7) ◽  
pp. 359-366 ◽  
Author(s):  
N Al‐Huniti ◽  
JC Nielsen ◽  
MM Hutmacher ◽  
J Lappalainen ◽  
K Cantagallo ◽  
...  
Keyword(s):  
Population Exposure ◽  
Exposure Response ◽  
Response Modeling

Selection of Patients with Hepatocellular Carcinoma for Sorafenib

2009 ◽  
Vol 7 (4) ◽  
pp. 397-403 ◽  
Author(s):  
Ghassan K. Abou-Alfa
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Phase Iii ◽  
Vegf Receptor ◽  
Raf Kinase ◽  
Advanced Cirrhosis ◽  
Phase Iii Studies ◽  
Selection Of Patients ◽  
Selection Of

Sorafenib, a multitargeted anti-VEGF receptor and raf kinase inhibitor, was recently approved by the FDA for treating unresectable hepatocellular carcinoma (HCC) based on 2 randomized phase III studies. In addition, a phase II study evaluating sorafenib in patients with HCC and Child-Pugh A and B and a phase I study evaluating sorafenib in patients with organ dysfunction have provided insight about the safety and efficacy of sorafenib in patients with HCC and more advanced cirrhosis, and any difference in outcome based on etiology of HCC. The lack of objective responses observed in the sorafenib arm in the SHARP study also raises practical issues about how to assess response or efficacy of the therapy and thus how long a patient should receive sorafenib. This article addresses these questions on the use of sorafenib in HCC, both in the locally advanced and metastatic settings, in addition to the potential future applications and uses of sorafenib.

Population Exposure-Response Modeling of Metformin in Patients With Type 2 Diabetes Mellitus

2008 ◽  
Vol 48 (6) ◽  
pp. 696-707 ◽  
Author(s):  
Ying Hong ◽  
Shashank Rohatagi ◽  
Bahru Habtemariam ◽  
Joseph R. Walker ◽  
Sherwyn L. Schwartz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Population Exposure ◽  
Exposure Response ◽  
Response Modeling

Population exposure-response modeling of oral Nepadutant administration in Colicky infants

2015 ◽  
Vol 37 (8) ◽  
pp. e115
Author(s):  
P. Mazzei ◽  
E.N. Jonsson ◽  
S. Jönsson ◽  
S. Bouchene ◽  
M.O. Karlsson ◽  
...  
Keyword(s):  
Population Exposure ◽  
Exposure Response ◽  
Response Modeling
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