BACKGROUND AND OBJECTIVE: Omecamtiv mecarbil (OM) is a cardiac myosin activator under clinical development for the treatment of heart failure. Two modified-release (MR) novel OM minitablet formulations were developed to support the planned investigation of chronic heart failure in pediatric patients. The primary objective of this study was to determine the bioavailability of the minitablets relative to the adult matrix MR formulation tablets. METHODS: In a randomized, 5-period, crossover study, 20 healthy subjects received each of the following treatments orally: one 25-mg adult matrix MR tablet, 25 1-mg slow-release minitablets, 25 1-mg fast-release minitablets, six 1-mg slow-release minitablets, or six 1-mg fast-release minitablets after an overnight fast of at least 10 h with a minimum washout of 7 days between treatments. Blood samples were collected for up to 168 h. OM pharmacokinetic parameters were estimated using non-compartmental methods. RESULTS: When OM was administered as 25 1-mg OM slow-release minitablets, AUClast, AUCinf, and Cmax were 0.998-, 1.00-, and 1.29-fold of a single 25-mg OM matrix MR tablet, respectively. When OM was administered as 25 1-mg OM fast-release minitablets, AUClast, AUCinf, and Cmax were 1.26-, 1.25-, and 2.21-fold of a single 25-mg OM matrix MR tablet, respectively. The slow- and fast-release minitablets display approximately dose-proportional pharmacokinetics. There were no serious adverse events or treatment-emergent adverse events leading to discontinuation from the study. CONCLUSIONS: Relative bioavailability of slow-release minitablets was demonstrated to be similar to the adult matrix MR formulation.
RCT Entities:
BACKGROUND AND OBJECTIVE: Omecamtiv mecarbil (OM) is a cardiac myosin activator under clinical development for the treatment of heart failure. Two modified-release (MR) novel OM minitablet formulations were developed to support the planned investigation of chronic heart failure in pediatric patients. The primary objective of this study was to determine the bioavailability of the minitablets relative to the adult matrix MR formulation tablets. METHODS: In a randomized, 5-period, crossover study, 20 healthy subjects received each of the following treatments orally: one 25-mg adult matrix MR tablet, 25 1-mg slow-release minitablets, 25 1-mg fast-release minitablets, six 1-mg slow-release minitablets, or six 1-mg fast-release minitablets after an overnight fast of at least 10 h with a minimum washout of 7 days between treatments. Blood samples were collected for up to 168 h. OM pharmacokinetic parameters were estimated using non-compartmental methods. RESULTS: When OM was administered as 25 1-mg OM slow-release minitablets, AUClast, AUCinf, and Cmax were 0.998-, 1.00-, and 1.29-fold of a single 25-mg OM matrix MR tablet, respectively. When OM was administered as 25 1-mg OM fast-release minitablets, AUClast, AUCinf, and Cmax were 1.26-, 1.25-, and 2.21-fold of a single 25-mg OM matrix MR tablet, respectively. The slow- and fast-release minitablets display approximately dose-proportional pharmacokinetics. There were no serious adverse events or treatment-emergent adverse events leading to discontinuation from the study. CONCLUSIONS: Relative bioavailability of slow-release minitablets was demonstrated to be similar to the adult matrix MR formulation.
Authors: John R Teerlink; G Michael Felker; John J V McMurray; Piotr Ponikowski; Marco Metra; Gerasimos S Filippatos; Justin A Ezekowitz; Kenneth Dickstein; John G F Cleland; Jae B Kim; Lei Lei; Beat Knusel; Andrew A Wolff; Fady I Malik; Scott M Wasserman Journal: J Am Coll Cardiol Date: 2016-03-29 Impact factor: 24.094
Authors: John R Teerlink; Cyril P Clarke; Khalil G Saikali; Jacqueline H Lee; Michael M Chen; Rafael D Escandon; Lyndsey Elliott; Rachel Bee; Mohammad Reza Habibzadeh; Jonathan H Goldman; Nelson B Schiller; Fady I Malik; Andrew A Wolff Journal: Lancet Date: 2011-08-20 Impact factor: 79.321
Authors: John R Teerlink; G Michael Felker; John J V McMurray; Scott D Solomon; Kirkwood F Adams; John G F Cleland; Justin A Ezekowitz; Assen Goudev; Peter Macdonald; Marco Metra; Veselin Mitrovic; Piotr Ponikowski; Pranas Serpytis; Jindrich Spinar; János Tomcsányi; Hans J Vandekerckhove; Adriaan A Voors; Maria Laura Monsalvo; James Johnston; Fady I Malik; Narimon Honarpour Journal: Lancet Date: 2016-12-01 Impact factor: 79.321
Authors: Rameshraja Palaparthy; Christopher Banfield; Paco Alvarez; Lucy Yan; Brian Smith; Jessica Johnson; Maria Laura Monsalvo; Fady Malik Journal: Int J Clin Pharmacol Ther Date: 2016-03 Impact factor: 1.366
Authors: John R Teerlink; Rafael Diaz; G Michael Felker; John J V McMurray; Marco Metra; Scott D Solomon; Kirkwood F Adams; Inder Anand; Alexandra Arias-Mendoza; Tor Biering-Sørensen; Michael Böhm; Diana Bonderman; John G F Cleland; Ramon Corbalan; Maria G Crespo-Leiro; Ulf Dahlström; Luis E Echeverria Correa; James C Fang; Gerasimos Filippatos; Cândida Fonseca; Eva Goncalvesova; Assen R Goudev; Jonathan G Howlett; David E Lanfear; Mayanna Lund; Peter Macdonald; Vyacheslav Mareev; Shin-Ichi Momomura; Eileen O'Meara; Alexander Parkhomenko; Piotr Ponikowski; Felix J A Ramires; Pranas Serpytis; Karen Sliwa; Jindrich Spinar; Thomas M Suter; Janos Tomcsanyi; Hans Vandekerckhove; Dragos Vinereanu; Adriaan A Voors; Mehmet B Yilmaz; Faiez Zannad; Lucie Sharpsten; Jason C Legg; Siddique A Abbasi; Claire Varin; Fady I Malik; Christopher E Kurtz Journal: Eur J Heart Fail Date: 2020-10-27 Impact factor: 15.534