Trial designs for multicentre clinical studies of investigational phases I B to III with praziquantel.

Following very promising results with 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a] isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide) in animal experiments on toxicity and efficacy and after confirming excellent tolerability in healthy volunteers, WHO could be won over to the further clinical development of this compound. In close cooperation trial protocols and case report sheets standardised as far as possible were set up for intercontinental multicentre trials in investigational phases II A, II B, and III, respectively. Thus, in investigational phase II A, studies were conducted simultaneously in Africa, Asia and South America. In all those endemic areas not only good tolerability in patients but also high efficacy against local Schistosoma species could be confirmed in double blind trials. In the extended phase II B, patients were allotted to 3 strata of different intensity of infection in order to find out if differentiating dosages would be necessary according to degree of worm burden, patient's age, and occurrence of more frequent and/or severe adverse reactions in patients with hepatolienal complications. There is not yet a satisfactory answer to all of these questions. In the investigational phase III already under way we hope to fill those gaps and also to find the optimum dosage for large scale use under field conditions. The profile of praziquantel, however, has already been established to an extent that first community health projects have been successfully started and others are in an advanced stage of planning.