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Model‐Supported Development of CS‐8635: A Fixed‐Dose Combination of Olmesartan, Amlodipine, and Hydrochlorothiazide
Author(s) -
Song SaeHeum,
Carrothers Timothy J.,
Moore Helen,
Green Michelle,
Miller Raymond,
Rohatagi Shashank,
Lee James,
Wang Antonia,
Melino Michael,
Patel Manini,
Heyrman Reinilde,
Salazar Daniel E.
Publication year - 2013
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.17
Subject(s) - olmesartan , hydrochlorothiazide , medicine , amlodipine , blood pressure , fixed dose combination , pharmacology , urology
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.