Two pharmaceutical companies terminated a cardiovascular outcomes study earlier at the request of the trial’s steering committee.
The study compared naltrexone hydrochloride and bupropion hydrochloride extended-release tablets (Contrave) with placebo in nearly 9,000 overweight and obese patients. However, Takeda and Orexigen, the manufacturers of naltrexone hydrochloride and bupropion hydrochloride, announced on May 12 that they halted the study.
In 2014, the FDA approved naltrexone hydrochloride and bupropion hydrochloride as an adjunct to diet and exercise in overweight and obese patients. The FDA required the companies conduct a postmarketing study evaluating the drug’s long-term effects on the incidence of major adverse cardiovascular events.
Steven Nissen, MD, of the Cleveland Clinic, was the study’s lead author. In a news release on May 12, the Cleveland Clinic said the FDA found that Orexigen had violated agreements when the company shared preliminary results with individuals and business partners. Orexigen then disclosed the interim analysis in a public filing in March.
The Cleveland Clinic announced more results on May 12 after the study was 50 percent complete. It said that 90 patients in the naltrexone hydrochloride and bupropion hydrochloride group and 102 patients in the placebo group had reached the primary endpoint of cardiovascular death, stroke or MI. The difference was not statistically significant.
During the first 25 percent of the study, 59 cardiovascular events occurred in the placebo treatment group and 35 events in the Contrave group. During the second 25 percent of the study, 43 cardiovascular events occurred in the placebo group and 55 events occurred in the Contrave group, according to the Cleveland Clinic.
“These results show neither benefit nor harm for patients taking the drug, but are consistent with the requirement by the FDA that the Light Trial demonstrate an absence of a doubling of cardiovascular risk for patients taking the drug,” Nissen said in a news release. “The inconsistency of effects on cardiovascular outcomes between the first 25 percent and the second 25 percent of the Light Study clearly illustrates the risks inherent in pre-judgment of clinical trial results based upon an interim analysis and demonstrate why interim results should remain confidential during any ongoing trial.”