At the 26th North American ISSX and 39th JSSX Meeting in September 2024, Quotient Sciences presented three posters showcasing significant advancements in the pharmacokinetics and metabolism research of acoziborole. Acoziborole is a potentially transformative investigational treatment for Human African trypanosomiasis (HAT), commonly known as sleeping sickness.
This is an illness caused by protozoan parasites transmitted by infected tsetse flies. It is endemic in sub-Saharan Africa and without treatment is typically fatal. Most people impacted by HAT live in rural areas and depend on agriculture, fishing, animal husbandry or hunting.
Continue reading to see how Quotient Sciences supported the radiosynthesis and GMP repurification of 14C drug substance of oxaborole-6 carboxamide, followed by the ADME studies in healthy subjects.
Poster 1: Mass Balance Recovery, Absorption, Metabolism, and Excretion of [14C]Acoziborole – Preparation of GMP [14C]Acoziborole Drug Substance
This poster outlines the radiolabelling and purification process for [14C]acoziborole, a radiolabelled drug produced under GMP standards to support human metabolism studies. It outlines the synthesis process, including the initial non-GMP preparation from barium [14C]carbonate and the subsequent GMP repurification conducted in a dedicated radiosynthesis laboratory. This process ensures that the final product meets regulatory standards through thorough quality control and assurance measures. As a result of the careful synthesis and purification, the final product is a GMP-compliant [14C]acoziborole, now ready for use in human studies.
Access the full poster for more on the process and outcomes.
Poster 2: A Single Dose Study to Assess the Mass Balance Recovery, Absorption, Metabolism, and Excretion of [14C]Acoziborole in Healthy Male Subjects
A Phase 1 open-label clinical study was conducted to examine the mass balance, pharmacokinetics, metabolism, and excretion of acoziborole. The study involved six healthy male participants and provided key insights into how the drug is processed in the body. This study was funded and sponsored by DNDi in Geneva, Switzerland, and conducted by Quotient Sciences at our integrated drug product formulation development, drug product manufacturing, and clinical pharmacology facility in Nottingham, UK.
In this study, participants received a single oral dose of 960 mg [14C]-acoziborole. Over the next 120 days, researchers collected samples of blood, plasma, urine, and faeces to evaluate the drug's absorption and elimination. However, the study encountered challenges due to the COVID-19 pandemic, which restricted urine collections to just 16 days post-dose.
Key findings indicate that acoziborole was well tolerated, demonstrating good absorption with predominantly slow biliary-faecal elimination and minimal urinary excretion. Notably, acoziborole was the most abundant circulating component in plasma. This poster describes the mass balance and clinical safety assessments from the human ADME study.
Download the full poster to explore the detailed methodology and findings.
Poster 3: Investigation of the Metabolite Profile of Acoziborole in Plasma, Urine, and Fecal Homogenate Samples Using UPLC-MS Fractionation Followed by AMS Analysis
This poster focuses on the analysis of metabolites following a human ADME study that used a microdose of [14C]-acoziborole. To accurately assess the metabolites present at such low doses, Accelerator Mass Spectrometry (AMS) was employed. The research involved preparing pools of plasma, urine, and faeces homogenates to investigate the metabolites. Using a sophisticated analysis method called data-dependent acquisition, the study detected metabolites in these samples and assigned them to specific fractions where their activity exceeded baseline levels, based on their molecular mass. This research contributes to our understanding of the drug’s metabolic pathway, its safety profile in humans, and its potential as an effective treatment for HAT.
For a breakdown of the methodology and results, access the full poster.
