Phase I Clinical Testing. Antimalarial Drugs.

Abstract : The two drugs subjected to Phase I clinical testing were Mefloquine and WR 184806-H3PO4, another quinoline methanol. A chronic safety and tolerance study of mefloquine was initiated. Fifty subjects will receive 500 mg mefloquine or placebo weekly for 52 weeks. Clinical, ophthalmologic, hematologic and biochemical monitoring are performed serially. During the initial weeks of study no adverse reactions have been observed. Studies are also approved to determine the top tolerated single oral dose of mefloquine and the safety and tolerance of mefloquine when administration of a single 'therapeutic' oral dose level is repeated 7 days after the first administration. The first administration of WR 184806-H3PO4 to humans has been made. Single oral doses were well tolerated to the 1000 mg level six subjects receiving 1200 to 1400 mg all developed intolerance manifested by combinations of light-headedness with associated difficulties such as concentrating and focusing, headache, nausea, insomia, and unusual dreams. In all subjects the symptoms were non-incapacitating and lasted less than 24 hours. Multiple oral doses were then tested administering drug or placebo every 8 hours for 72 hours. Intolerance manifestations were similar to those observed in the single dose study and occurred at the 3600 mg total dose level (400 mg/individual dose).