BioWorld International Correspondent

LONDON - GW Pharmaceuticals plc has negotiated all the legal requirements of the U.S. Drug Enforcement Agency to launch a Phase II/III trial of its cannabis-based medicine Sativex in treating opioid-resistant cancer pain at 40 centers across the country.

"This is a vast undertaking, and it is the first time a trial of such scale has been undertaken in an Class 1 drug in the U.S.," Justin Gover, managing director told BioWorld International. "It is difficult to overestimate the importance of this and the complexity involved in importing a Class 1 drug and setting up [the trial]."

The DEA had to inspect and write a report on all 40 sites. "We had to make specific provisions for the storage and dispensing of the drug in each center, and it all had to be signed off in Washington," Gover said.

Before approaching the DEA, GW Pharma, of Salisbury, UK, had to secure IND approval from the FDA. Gover said the company has been paving the way for this more than seven years, ensuring regulators were aware of the progress of Sativex. "It's part and parcel of building the relationship," he said. "We need to ensure this medicine is properly understood."

The Phase II/III dose-ranging trial will evaluate the efficacy and safety of Sativex in the treatment of pain in patients with advanced cancer, who do not get adequate relief with opioid therapy.

The five-week, placebo-controlled study will recruit 336 patients, with results expected toward the end of 2008. The primary objective is to evaluate the potential role and dose range of Sativex as an adjunct to pre-existing pain medications.

The principal investigator Russell Portenoy, chairman of the department of pain medicine and palliative care at Beth Israel Medical Center in New York City, said, "Studies suggest that more than one-third of patients with cancer, and more than three-quarters of those with advanced disease, have chronic pain. Large surveys indicate that optimal opioid therapy does not yield sufficient relief in a substantial proportion of these patients."

The trial, and the rest of the U.S. development program, is being paid for by GW Pharma's partner Otsuka Pharmaceutical Development and Commercialization Inc., of Tokyo.

Sativex, which is composed primarily of two cannabinoids, cannabidiol and delta 9 tetrahydrocannabinol, will be administered as a metered dose oro-mucosal spray. Although Sativex has completed multiple trials elsewhere, this is the first one to have a dose-ranging element.

"Other studies have been self-titrated, but Otsuka thought it would be prudent to introduce dose ranging," Gover said.

The trial will extend data from a previous, two-week European clinical trial in 177 patients in which 43 percent of those who received Sativex, while remaining on opioids, had at least a 30 percent decrease in their pain score. This compared to 21 percent of patients receiving placebo and opioids.