The Rennes university hospital announced the man's death on Sunday.
He had been admitted a week earlier suffering from side-effects incurred during a trial for a pain and mood disorder medication developed by a Portuguese company, Bial, and tested at the Biotrial private laboratory in the western French city.
The five other men who had taken the highest dose of the drug remained in hospital on Sunday.
Three of them were suffering a "handicap that could be irreversible" and another had neurological problems, the neurology department head, Pierre-Gilles Edan, said on Friday.
The other had shown no symptoms but was being monitored.
The 84 other volunteers exposed to the drug have all been contacted and 10 came to the hospital for check-ups but did not show the same "anomalies" as the hospitalised patients, a statement said.
Bial is cooperating with the investigation and vows it followed "international best practice" in developing the drug.