27 research outputs found
Randomized Controlled Trial of RTS,S/AS02D and RTS,S/AS01E Malaria Candidate Vaccines Given According to Different Schedules in Ghanaian Children
Background:The target delivery channel of RTS,S candidate malaria vaccines in malaria-endemic countries in Africa is the World Health Organisation Expanded Program on Immunization. As an Adjuvant System, age de-escalation and schedule selection step, this study assessed 3 schedules of RTS,S/AS01E and RTS,S/AS02D in infants and young children 5–17 months of age in Ghana.Methodology:A Phase II, partially-blind randomized controlled study (blind to vaccine, not to schedule), of 19 months duration was conducted in two (2) centres in Ghana between August 2006 and May 2008. Subjects were allocated randomly (1:1:1:1:1:1) to one of six study groups at each study site, each defining which vaccine should be given and by which schedule (0,1-, 0,1,2- or 0,1,7-months). For the 0,1,2-month schedule participants received RTS,S/AS01E or rabies vaccine at one center and RTS,S/AS01E or RTS,S/AS02D at the other. For the other schedules at both study sites, they received RTS,S/AS01E or RTS,S/AS02D. The primary outcome measure was the occurrence of serious adverse events until 10 months post dose 1.Results:The number of serious adverse events reported across groups was balanced. One child had a simple febrile convulsion, which evolved favourably without sequelae, considered to be related to RTS,S/AS01E vaccination. Low grade reactions occurred slightly more frequently in recipients of RTS,S/AS than rabies vaccines; grade 3 reactions were infrequent. Less local reactogenicity occurred with RTS,S/AS01E than RTS,S/AS02D. Both candidate vaccines were highly immunogenic for anti-circumsporozoite and anti-Hepatitis B Virus surface antigen antibodies. Recipients of RTS,S/AS01E compared to RTS,S/AS02D had higher peak anti-circumsporozoite antibody responses for all 3 schedules. Three dose schedules were more immunogenic than 2 dose schedules. Area under the curve analyses for anti-circumsporozoite antibodies were comparable between the 0,1,2- and 0,1,7-month RTS,S/AS01E schedules.Conclusions:Both candidate malaria vaccines were well tolerated. Anti-circumsporozoite responses were greater with RTS,S/AS01E than RTS,S/AS02D and when 3 rather than 2 doses were given. This study supports the selection of RTS,S/AS01E and a 3 dose schedule for further development in children and infants
Formulation And Evaluation of a Combined Chloroquine Phosphate and Chlorpheniramine Maleate Product
Chloroquine phosphate granules (B1) and chlorpheniramine maleate granules (B2) were separately formulated with maize starch and lactose with polyvinylpyrrolidone (10% w/v) as binder. B1 was coated with 5% w/v ethylcellulose to varying degrees by increasing the spray time of the coating solution by 2 minutes between successive batches to produce B1A, B1B, B1C, B1D, B1E, B1F, B1G, B1H and B1I of increasing coat thickness. B2 was not coated. The release profiles of the coated and uncoated granules were studied using the US Pharmacopoeia XXIV (2000) dissolution apparatus II. The release profiles showed a significant and progressive retardation of the release of chloroquine phosphate from B1A to B1I as the coating time was increased. Batch B1I which gave the most desired release profile was selected and combined with the chlorpheniramine maleate granules, encapsulated and the release profiles studied. Each capsule contained granules equivalent to 4mg chlorpheniramine maleate (uncoated) and 250mg chloroquine phosphate (coated). Almost all the chlorpheniramine (97.4%) in the combined product (capsule) was released in 35 min while only about a quarter (24.4%) of the chloroquine component was released in the same period. The combined formulation appears to possess the ability to protect susceptible patients from chloroquine-induced itching by releasing a greater amount of the antihistamine before the chloroquine is released. Journal of Science and Technology Vol. 26 (3) 2003: pp. 32-3