FDA Approves Liquid Formulation of THC-Containing Drug for CINV

The U.S. Food and Drug Administration (FDA) approved Syndros (dronabinol oral solution) on Tuesday for the treatment of patients experiencing chemotherapy-induced nausea and vomiting (CINV) who have not responded to conventional antiemetic therapies. The agent is also indicated for treating anorexia associated with weight loss in patients with AIDS.

Insys Therapeutics, Inc., the pharmaceutical company developing the drug, announced in a press release that Syndros would be available “in the second half of 2016.”

Syndros is a liquid version of Marinol (dronabinol) soft gel capsules and contains tetrahydrocannabinol (THC), the primary active compound in cannabis (marijuana). Marinol is developed by AbbVie Inc.

“Syndros is the first and only FDA-approved dronabinol solution for oral use. It is a liquid that is easy to swallow and allows for the dosage to be titrated to clinical effect,” John N. Kapoor, chairman, CEO and president of Insys, said in a statement, adding that, “once Syndros has been opened, it does not need to be refrigerated for 28 days.”

Syndros’ approval was based on a phase 1 trial looking at the bioequivalence and pharmacokinetics of the drug compared with Marinol. In the study, over 50 healthy volunteers received both the new oral formulation and capsules in different sequences. The effects of food and fasting on both formulations were analyzed.

The two formulations were determined to be bioequivalent in several areas among patients receiving the agent after fasting overnight. Detectable plasma dronabinol levels were seen after 15 minutes in 100 percent of patients receiving the oral formulation compared with less than 25 percent of patients receiving the capsule formulation. Further, variability among patients was lower (13.5 percent) with the oral formulation compared with capsules (36.8 percent).

Among patients who had eaten, initial dronabinol absorption was also more rapid with the oral solution (9 minutes) compared with capsules (about two hours). After 30 minutes, 100 percent of individuals receiving the liquid formulation had detectable plasma dronabinol levels, compared with 15 percent of those receiving the capsule formulation.

These trial findings were reported at the recent annual meeting of the American Society of Clinical Oncology, with the researchers noting that the new oral solution, “may provide a more flexible administration option as well as a more rapid absorption and lower intra-patient variability compared with the capsule formulation.”

According to the company’s press release following Syndros’ approval, the agent “may cause psychiatric and cognitive effects and impair mental and/or physical abilities. Patients with cardiac disorders may experience hypotension, hypertension, syncope or tachycardia.”

Further, this safety information states that physicians should assess patients for risk of abuse or misuse in patients with a history of substance abuse or dependence.

Insys first submitted a New Drug Application (NDA) for Syndros in August 2014, but was rejected two months later for providing an inadequate plan to study the safety and efficacy of the agent in pediatric patients. In June 2015, the company submitted an NDA again, which was accepted by the FDA in August 2015. In late March 2016, the FDA announced that it had received new, non-clinical information from Insys and would extend its decision date three months, from April 1 to July 1, 2016.