Development of a rectal antibiotic formulation for the community-based management of neonatal sepsis

Organization: 
University of Oxford, Nuffield Dept of Clinical Medicine
Organization Location: 
Oxford, England

Neonatal sepsis is the single greatest cause of preventable death in children living in tropical countries. Most deaths occur in or near home. Prompt parenteral administration of effective antibiotics is life saving, but seldom possible in the rural tropics. We propose to develop a rectal formulation of a third generation cephalosporin antibiotic for reducing mortality through early community-based management of neonatal sepsis. We will carry out pharmaceutical and preclinical studies with the aim of developing a stable rectal formulation of a candidate antibiotic with adequate bioavailability. Selection will depend on activity against causative pathogens, a good safety profile, and central nervous system penetration. The lead compound type now is a 3rd generation cephalosporin. Following preclinical studies, acceptable bioavailability in humans would be confirmed by a Phase 1 study in healthy adult volunteers. If successful, further funding would be sought for a full development program; regulatory Phase 1, Phase 2 trials in infants, then large Phase 3 trials to assess the impact on neonatal mortality. Rectal administration is a simple, safe, and acceptable method of treating sick children. It would be suitable for the community-based management of neonatal sepsis if an appropriate antibiotic could be provided in a stable and adequately bioavailable formulation which could save millions of infant lives each year. We are requesting seed level funding (250 000 USD) over two years in order to conduct pharmaceutical research to develop this formulation, perform preliminary animal studies, and then an exploratory Phase 1 study in healthy normal volunteers.