Orexigen submitted a
New Drug Application (NDA) for the combination to the FDA in March 2010. Having paid a fee under the
Prescription Drug User Fee Act, Orexigen was given a deadline for the FDA to approve or reject the drug of January 2011. In December 2010, an FDA Advisory Committee voted 13-7 for the approval of Contrave and voted 11-8 for the conduct of a post-marketing cardiovascular outcomes study. Subsequently, on 2 February 2011, the FDA rejected the drug and it was decided that an extremely large-scale study of the long-term cardiovascular effects of Contrave would be needed, before approval could be considered. It was ultimately approved in the United States in 2014. In December 2014, the
Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency endorsed the combination for licensure as an obesity medication when used alongside diet and exercise. Authorization was granted in March 2015. In May 2015, Orexigen prematurely ended the trial that was intended to test whether naltrexone/bupropion increased the risk of
major adverse cardiovascular events in obese patients with cardiovascular disease because an independent panel of experts said that the drug maker "inappropriately" compromised the trial by prematurely releasing interim data. The early data release reported a reduction in heart attacks, but that advantage was no longer observed when a more complete view of the data was analyzed. The company then initiated a second trial (CONVENE) designed to test this outcome in 2016, but it was terminated in 2016 shortly after Takeda announced that it would sell its rights to the drug in the USA to Orexigen. In 2018, Orexigen sold its assets, including Contrave, to Nalpropion Pharmaceuticals. ==Society and culture==