The once-a-day tablet called Red heart pill combines four different medicines - aspirin, a statin to lower cholesterol, and an ACE inhibitor and a thiazide to counter high blood pressure in one tablet.
Seven hundred volunteers have been recruited in six countries for a 12-week pilot trial. If all goes well, the main trial with 5,000 to 7,000 volunteers will begin at the end of next year.
Anthony Rodgers, co-director of the clinical trials unit at the University of Auckland, leader of the project, said it had been a struggle to get the polypill this far.
"The chances of mainstream pharmaceutical industry taking this on are slim," the Guardian quoted him as saying.
"We spent a few years around about 2000-2002 trying to persuade a number of companies to do this, but got nowhere. Basically, their whole business model is around people paying a few hundred pounds a year for the latest blockbuster drug.
"A pill with established medicines that halved cardiovascular risk and could be available for ?20 a year could be seen as a threat," he added.
"There are particular groups in our community who are not getting the required preventive therapy, both among those at modest cardiovascular risk who are not being evaluated and those at pretty serious risk who have already had a heart attack," said Professor Simon Thom, from the international centre of circulatory health at Imperial College London, where the UK arm of the trial is taking place and where the first volunteer will begin taking the tablets this week.
The research teams, with the backing in the UK of the Wellcome Trust and the British Heart Foundation, are just a few years away from making the polypill an accessible reality.