Tetlow, Michelle, Simon, Francois, Dumont, Etienne, Cota, Glaucia, Lyon, Rebecca, Dixon, Jan, Dickinson, Laura 
ORCID: 0000-0001-5557-9396, Else, Laura, Gibney, Jennifer, Stackpoole, Michael et al (show 18 more authors)
(2026)
A phase I double-blind, placebo-controlled (Part B only), randomised trial to evaluate the safety, tolerability, and pharmacokinetics of single dose in fed state, and repeat doses of DNDI-6899 in healthy participants
Wellcome Open Research, 11.
430-.
ISSN 2398-502X, 2398-502X
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DNDI-6899 Protocol Manuscript v1.0, 29th May 2026.pdf - Submitted version Download (456kB) | Preview |
Abstract
Background Visceral Leishmaniasis (VL) – also known as Kala-azar – is a disease caused by obligate intracellular protozoan parasites, particularly the species Leishmania donovani and Leishmania infantum. VL causes fever, weight loss, severe haematological damage, spleen and liver enlargement, and, if left untreated, cases of VL are typically fatal. Despite the significant change in the epidemiology of the disease in recent years, VL remains a major problem in Africa but also in the Americas. The main barrier to the elimination goal refers to the difficulty in offering accessible, effective and safe treatments. While therapies are available to treat the disease, none are ideal for use in resource poor settings where the disease is endemic, due to the unfavourable safety profile of drugs, logistical complexity and cost. As such there is a real unmet medical need for new, short course oral drugs for the treatment of this disease. DNDI-6899 is a novel pyrazolopyrimidine derivative that has the potential to be effective against VL. Methods This is a first in human clinical investigation with Food Effect (Part A) and Double-Blind Multiple Ascending Dose (Part B) in healthy participants. In Part A, 12 participants will be randomised to fed or fasted conditions (treatment period 1) and dosed with DNDI-6899. The same participants will then be treated under opposite conditions (treatment period 2) after an appropriate washout period. In Part B, participants will be randomised to either DNDI-6899 or placebo in either fed or fasted conditions. Treatment conditions in Part B will depend on the results in Part A. All participants will provide written informed consent. Conclusions This trial will assess the safety, tolerability, and pharmacokinetics of single and repeat doses of DNDI-6899 in healthy participants. International Standard Randomised Control Trial Number (ISRCTN) registration: https://www.isrctn.com/ISRCTN31974125
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 32 Biomedical and Clinical Sciences, 3202 Clinical Sciences, Infectious Diseases, Clinical Trials and Supportive Activities, Clinical Research, Vector-Borne Diseases, Rare Diseases, Orphan Drug, 6.1 Pharmaceuticals, Infection, 3 Good Health and Well Being |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology (T&R Staff) Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > SMIB Professional Services Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Pharmacology & Therapeutics |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 13 Aug 2026 09:52 |
| Last Modified: | 13 Aug 2026 09:52 |
| DOI: | 10.12688/wellcomeopenres.26924.1 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3199921 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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