Model-Supported Development of CS-8635: A Fixed-Dose Combination of Olmesartan, Amlodipine, and Hydrochlorothiazide.
CS-8635, a fixed-dose triple combination of olmesartan, amlodipine, and hydrochlorothiazide, was developed to address the growing need for additional blood pressure (BP) reduction in patients not controlled with dual-combination therapies. Prior to Phase III, modeling and simulation (M&S) was conducted to estimate the additional BP lowering effect of CS-8635 compared to the respective dual combinations. The Phase III study evaluated CS-8635 BP lowering effects only at the highest dose strength among the five dose strengths to be developed. Post-trial M&S was performed using an integrated dataset from three Phase III programs; CS-8635 plus two prior dual combinations. M&S robustly estimated and described the BP lowering effects of CS-8635 evaluated in a clinical setting. Furthermore, M&S evaluated BP lowering effects of the additional four dose strengths not studied. In summary, M&S aided the development of the clinical study and full characterization of the BP lowering effects of CS-8635 across intermediate doses.
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
SaeHeum
S
Song
Pharsight, a Certara Company, Sunnyvale, CA, USA.
Timothy J
TJ
Carrothers
Pharsight, a Certara Company, Sunnyvale, CA, USA.
Helen
H
Moore
Pharsight, a Certara Company, Sunnyvale, CA, USA.
Michelle
M
Green
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Raymond
R
Miller
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Shashank
S
Rohatagi
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
James
J
Lee
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Antonia
A
Wang
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Michael
M
Melino
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Manini
M
Patel
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Reinilde
R
Heyrman
Daiichi Sankyo Pharma Development, Edison, NJ, USA.
Daniel E
DE
Salazar
amlodipine; angiotensin inhibitor; hydrochlorothiazide; hypertension; modeling and simulation; olmesartan