Phase III clinical trials with praziquantel in S. japonicum infections in the Philippines.

ABSTRACT

Following successful Phase II clinical studies with praziquantel (2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino [2,1-a]isoquinolin-4-one, EMBAY 8440, Biltricide), expanded field trials of Phase III were conducted in Mindoro Oriental, Leyte and Davao Norte, to reassess efficacy, safety and acceptability of the drug on a larger scale. A total of 6,134 cases were treated with the best tolerated and effective dose of 60 mg/kg bwt which for practical purposes was given in 2 instead of 3 divided doses as applied in the earlier trials. Two aliquots of one stool from each individual were examined quantitatively by a modification of the thick smear method one week before, six and twelve months after treatment. Although 67.8% were noted to have drug-related side effects, most were mild to moderate, with only 1.2% considered as severe. Severe reactions consisted mainly of colicky abdominal pain, occurring about 1 h after drug intake, usually accompanied by fever, sweating, urge to defecate, and occasionally by discharge of bloody stool. These reactions, however, required only symptomatic treatment with antispasmodics and antipyretics. Stool follow-up 6 months after treatment showed 89.2% of EPG (eggs per gram of faeces) negativity, with an overall egg reduction of 91.1%. Twelve months after treatment, practically the same results were obtained with 87.5% still negative cases and an egg reduction of 90.5%. This study confirms safety and efficacy of the drug as well as its acceptability when given on a community wide scale.