Module 5 Presentations

05/07/2024

France clinical trial - BIA 10-2474 (3)

• For the single dose part of the study, the protocol describes eight groups of eight volunteers who were to receive single doses of BIA 10-2474 at 0.25, 1.25, 2.5, 5.0, 10, 20, 40 and 100 mg, with the possibility of additional groups to be added if no maximum tolerated dose was reached

• 6.1.2016 - 5 th cohort - 6 men received 50 mg dose/day

• 10.1.2016 - the first subject became ill on the evening of the 5th day of dosing and was hospitalized with the symptoms similar to stroke

• 11.1.2016, 8.00 the study team dispense the drug to additional 7 men

• 11.1.2016 in the morning the condition of the first subject deteriorated and he went to coma

• 11.1.2016 in the afternoon the study is suspended

• 17.1.2016 the first subject was declared dead

The Organisation for Professionals in Regulatory Affairs

BIA 10-2474

41

France clinical trial - BIA 10-2474 (4)

• Four subjects in the same cohort were also hospitalized with the similar complaints. • The opinion of the treating neurologist was that in 3 of the 4 men who had toxicity, the condition is such that an irreversible handicap is likely to occur despite of the institution of best possible treatment. • All these patients had hemorrhagic and necrotic lesions as seen on brain magnetic resonance imaging (MRI).

The Organisation for Professionals in Regulatory Affairs

BIA 10-2474

42

21