The pivotal phase 3 efficacy study randomized 322 patients after bunionectomy into one of four treatment groups: placebo, 0.5 mg t.i.d., 0.25 mg t.i.d., or 0.125 mg t.i.d. Sublingual buprenorphine was much more effective in reducing pain and SPID-48 scores, compared with placebo. Patients taking placebo had SPID-48 scores of 93.40, compared with 135.84, 125.75, and 182.81 for the 0.125-mg, 0.25-mg, and 0.5-mg SBS groups, respectively.
The most common adverse events were nausea, vomiting, and hypoxia. Specifically, in the pivotal study, nausea was reported at all three doses of 0.125 mg, 0.25 mg, and 0.50 mg in 43.9%, 58.8%, and 83.3% of patients.
Anne-Michelle Ruha, MD, of the University of Arizona, Phoenix, cited the risk of hypoxia as her biggest concern. “There’s so many factors that we can’t predict, like undiagnosed sleep apnea,” she said. “We just don’t know when the respiratory depression worsens, so I’m uncomfortable with the high rate of hypoxia.”
Although not directly related to this application, INSYS had been the subject of an investigation by the federal government in regard to an illegal marketing scheme that provided incentives for doctors to prescribe Subsys, a powerful and highly addictive synthetic opioid. Documents recently have been unsealed in federal court that prompted the federal government to investigate INSYS. The company has addressed the previous allegations of wrongdoing and states that INSYS has become a “... new and better company in many important respects across the organization,” according to a statement.The FDA usually follows the recommendations of its advisory panels, but they are not binding.