Another CV Outcomes Trial Testing Weight-Loss Drug Contrave Terminated Early
Yet another large-scale study testing the cardiovascular safety of the weight loss combination naltrexone-bupropion has been halted prematurely, TCTMD has confirmed.
The trial, known as CONVENE, was initially sponsored by Takeda Pharmaceuticals and was up and running for just a few months—it began on December 18, 2015—but was terminated last week, not long after the announcement Takeda would be selling the US rights of the controversial weight-loss drug, marketed as Contrave, to Orexigen.
CONVENE was designed to assess major adverse cardiovascular events, including cardiovascular death, nonfatal MI, and nonfatal stroke in obese patients with cardiovascular disease. Trial investigators had planned to enroll approximately 8,800 patients, and the results were expected in 2022. An Orexigen spokesperson told TCTMD that the decision to terminate the trial was announced by direct communication with clinical investigators participating in the trial.
It is the second cardiovascular outcomes study testing Contrave stopped before completion. LIGHT, which included 8,900 patients randomized to naltrexone/bupropion or placebo, broke down in 2015 over a premature public leak of interim data that compromised the trial. The disclosure of data from the study sponsors, specifically Orexigen, “fundamentally interfered” with the LIGHT trial, which led investigators to believe it was best to erase the scorecard and start again with a fresh trial.
Although CONVENE is now history, Orexigen is still required to conduct a large-scale cardiovascular outcomes study to satisfy the mandate set by the US Food and Drug Administration (FDA) when they approved the drug in 2014. Contrave was approved on the basis of positive trials showing the drug combination resulted in weight loss in obese or overweight individuals at high cardiovascular risk, but the approval was contingent on an additional outcomes trial being undertaken to prove the drug didn’t increase the risk of adverse cardiovascular events, such as MI or stroke.
More than 18 months since approval, and with two clinical trials already scuppered, that outcomes trial is yet to begin.
Orexigen issued a statement regarding the termination of CONVENE and said they plan to conduct a new cardiovascular outcomes study to satisfy the FDA requirement. As for why this trial was halted, the company said that after acquiring the US rights, which made them responsible for executing postmarketing development programs in the United States and in Europe, they planned to make changes to the postmarketing studies to meet their “global needs.”
“Transfer of the recently initiated multiyear CONVENE trial to Orexigen involves substantial complexity due to the scope, size, and nature of the study,” the statement reads. “In order for this trial to have continued under Orexigen sponsorship, a significant number of operational details would require reinitiation.”
Given the time needed to make these changes, and the few patients enrolled in CONVENE, Orexigen chose to terminate the study and start up a new trial with a revised protocol and new contracts. The company has notified the FDA of these changes and has told the agency they are committed to meeting their postmarketing requirements.