FDA Approves Dronabinol Solution to Treat CINV

John N. Kapoor, PhD

A dronabinol oral solution (Syndros) has been approved by the FDA as a treatment for patients with chemotherapy-induced nausea and vomiting (CINV) in those who have not responded to conventional antiemetic therapies, according to an announcement by Insys Therapeutics, Inc., the manufacturer of the drug.

The company estimates that the new oral solution formulation, which is a liquid version of Marinol (dronabinol) soft gel capsules and contains tetrahydrocannabinol (THC), the primary active compound in cannabis, will be available in the second half of 2016. Marinol is developed by AbbVie.

“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, PhD, 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.”

The approval of dronabinol oral solution was based on a phase I trial looking at the bioequivalence and pharmacokinetics of the drug compared with Marinol.^1,2 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% of patients receiving the oral formulation compared with less than 25% of patients receiving the capsule formulation. Further, variability among patients was lower (13.5%) with the oral formulation compared with capsules (36.8%).

Among patients who had eaten, initial dronabinol absorption was also more rapid with the oral solution (9 minutes) compared with capsules (about 2 hours). After 30 minutes, 100% of individuals receiving the liquid formulation had detectable plasma dronabinol levels, compared with 15% of those receiving the capsule formulation.

These trial findings were reported at the 2016 ASCO Annual Meeting, and the researchers noted 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.

References

1. Parikh N, Kramer WG, Khurana V, et al. A single-dose comparative bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers. J Clin Oncol. 2016; 34(suppl; abstr e21595).
2. Oh DA, Parikh N, Kramer WG, et al. Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers. J Clin Oncol. 2016; 34(suppl; abstr e21593).