COSMIC-HF A dose escalation study in patients with heart failure

• Research type

  Research Study

• Full title

  A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose Escalation Study to Select and Evaluate an Oral Modified Release Formulation of Omecamtiv Mecarbil in Subjects with Heart Failure and Left Ventricular Systolic Dysfunction

• IRAS ID

  117514

• Contact name

  Iain Squire

• Sponsor organisation

  Amgen Inc.

• Eudract number

  2012-000327-40

• ISRCTN Number

  N/A

• Research summary

  The study is a randomised, placebo-controlled, multicentre, phase 2 study in patients with heart failure and left ventriculareasystolic dysfunction. There are two phases to this study. The first phase, known as the dose escalation phase will involve 3 different oral formulations of AMG423 (omecamtiv mecarbil) all three of which will be taken in two doses. From this first phase an oral formulation that provides the optimal availability of AMG423 in the blood will be chosen. Two doses will also be chosen from this phase. These two doses in the optimal formulation will be used in the second phase of the study, the dose expansion phase. In this second expansion phase the two doses will be compared with placebo.The first patients to be enrolled onto the study will take part in the dose escalation phase. Once this phase is fully recruited and the dose and formulation has been chosen this escalation phase will close to patient entry. Subsequent patients will take part in the dose expansion phase. patientscan only take part in one phase of the study. The first dose escalation phase will require patients to take AMG423 or placebo orally twice daily for 7 days. Participation in the study will last 35 days. The first patients to enter the study in the dose escalation phase will start at the lowest dose of 25mg twice daily or the equivalent placebo. Pharmacokinetics data (a study of the way the body absoris, distributes, and gets rid of a drug) and safety data will be reviewed at the end of this dosing cohort before another cohort of patients opened. The next group of patientsrecruited will receive a higher dose of 50mg twice daily or the equivalent placebo. If optimal dose levels in patients are not achieved by these two cohorts, then the next set of patients will be entered at a dose level of 75mg twice daily or equivalent placebo. Data will be reviewed from each cohort by an independent committee before opening a higher dose cohort. patients who are enrolled following the closure of the first phase (the escalation phase) will be enrolled into the expansion phase of the study. One optimal formulation from the dose escalation phase and the optimal two doses will be compared versus placebo in approximately 300 patients patients will receive study product (AMG423 or placebo) for 12 weeks following screening. Total duration for a patient will be 16 weeks with a follow up call at 6 months.

• REC name

  South Central - Berkshire B Research Ethics Committee

• REC reference

  13/SC/0073

• Date of REC Opinion

  20 Mar 2013

• REC opinion

  Further Information Favourable Opinion