MICA: Developing a rectal formulation of ceftriaxone for community-based management of neonatal sepsis in low- and middle-income countries

MICA：开发头孢曲松直肠制剂，用于中低收入国家新生儿败血症的社区管理

• 批准号: MR/W021560/1
• 负责人: Elizabeth Ashley
• 金额: $ 171.62万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW021560%2F1
• 关键词: MICA; Developing; rectal; formulation; ceftriaxone

Neonatal sepsis (life-threatening infection in infants aged below 28 days of age) is the single greatest cause of preventable death in children living in tropical countries, being responsible for more than half a million of the estimated 2.4 million deaths that occur each year. Most deaths occur at or near home. Prompt administration of effective antibiotics by injection is life saving, but is usually not possible in the rural tropics where health centres are frequently several hours' journey away from home. Alternative strategies are needed to deliver effective treatment at the community level.Since 2012 we have worked on the pharmaceutical development of a suppository formulation of ceftriaxone. Ceftriaxone is an antibiotic used to treat severe infections, including meningitis, which has the advantage of being dosed just once day because it is a long-acting medicine. Our goal is to make effective community-based neonatal sepsis treatment feasible at low cost, and therefore used early and widely enough to prevent a substantial proportion of neonatal deaths from sepsis in high-burden low- and middle-income countries. We have developed several prototype suppositories already and we are ready to move testing into humans. We have an industrial partner (Orofino Pharmaceuticals) who has evaluated our candidate formulations for feasibility for industrial production and has lowered the cost of producing the absorption enhancer that will be combined with the antibiotic in the formulation. In this research project we plan to manufacture two different suppositories and assess how well they are absorbed in healthy adults in Thailand first. Based on absorption and safety results from this study we will then select the leading formulation to be tested in babies. We plan to give 60 babies who are in hospital under treatment for an infection one dose of the suppository in addition to their usual treatment and evaluate the absorption of antibiotic in the suppository. If ceftriaxone is absorbed adequately by this route and is well-tolerated, we will assess this formulation in large trials to measure impact on mortality, with the longer term goal of including the treatment in global treatment guidelines. This would pave the way for widespread uptake in high burden low- and middle-income countries.

新生儿败血症（28天以下婴儿的危及生命的感染）是热带国家儿童可预防死亡的最大单一原因，在每年估计发生的240万例死亡中，造成50多万例死亡。大多数死亡发生在家中或附近。及时注射有效抗生素可以挽救生命，但在热带农村通常是不可能的，因为那里的保健中心离家往往要几个小时的路程。需要其他战略在社区一级提供有效治疗。自2012年以来，我们一直致力于头孢曲松栓剂配方的药物开发。头孢曲松是一种用于治疗包括脑膜炎在内的严重感染的抗生素，它的优点是每天只需服用一次，因为它是一种长效药物。我们的目标是使有效的以社区为基础的低成本新生儿败血症治疗成为可能，从而在高负担的低收入和中等收入国家尽早和广泛使用，以防止很大比例的新生儿死于败血症。我们已经开发了几种栓剂原型，并准备在人体上进行测试。我们有一个工业合作伙伴（Orofino Pharmaceuticals），他们已经评估了我们的候选配方的工业生产可行性，并降低了生产吸收促进剂的成本，这种吸收促进剂将与配方中的抗生素结合使用。在这个研究项目中，我们计划首先制造两种不同的栓剂，并评估它们在泰国健康成年人中的吸收情况。根据这项研究的吸收和安全性结果，我们将选择领先的配方进行婴儿试验。我们计划给60名因感染住院治疗的婴儿在常规治疗的基础上再服用一剂栓剂，评估栓剂对抗生素的吸收情况。如果头孢曲松通过这种途径被充分吸收并且耐受性良好，我们将在大型试验中评估该配方，以衡量对死亡率的影响，长期目标是将该治疗纳入全球治疗指南。这将为高负担低收入和中等收入国家的广泛采用铺平道路。