French Cannibinoid Phase I Study Gone Wrong Save

Six volunteers were admitted to the University Hospital of Rennes in France last week after partaking in the Phase I trial of a new medication meant to treat mood disorders such as anxiety.

A Portuguese pharmaceutical company, Bial, is developing the product to regulate mood and appetite. BIA 10-2474 is an analgesic endocannibinoids that does not contain the extracts of the cannabis plant. It is an inhibitor of fatty acid amide hydrolase, or FAAH. The enzyme normally degrades and terminates the action of our naturally-occurring biochemicals that include ananadamide, a stimulator of the same receptors as the active components of marijuana. By prolonging the action of ananadamide, FAAH inhibitors have the potential to reduce pain and anxiety, among other neurological conditions.

The study was being conducted by the privately-owned Biotrial company on behalf of the drugmaker Biotrial, the largest pharmaceutical company in Portugal. Biotrial has its French headquarters in Rennes and also has a 150-bed facility in Rennes for such Phase I trials.

The trial began in July 2015; the six men who fell ill started taking the drug on January 7 and the first patient began showing negative symptoms on January 10. Bial halted the trial a day later. Nearly 120 normal healthy subjects were enrolled in the trial – 90 on drug and about 30 on placebo.

As part of the phase I trial, subjects were given varying doses and the six men admitted to the hospital were in the group who were taking the drug “regularly”. Those hospitalized were men, aged between 28 and 49 years. One man was initially reported to be clinically brain dead but has since died on January 17. Three others suffered from irreversible neurological problems. The sixth volunteer had no symptoms but was being monitored.

The study drug molecule had previously been tested on chimpanzees and was now being used in humans.

In a statement, the Portuguese firm insisted it had followed “international best practice” in developing the drug and said it would cooperate with the investigation to “determine in a rigorous and exhaustive manner” what had happened. The Paris prosecutor’s office said an investigation had been opened.

The British Medical Journal reported in a meta-analysis of noncancer Phase 1 drug trials that showed serious adverse events (SAE) occurred in only 0.31 percent of participants, and no deaths.

Nonetheless, the unfortunate reports of this suspended trial in France will raise safety questions for other trials and challenge regulators to develop measures to better protect those participating in clinical trials.