Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers

Author:

Sinxadi Phumla12,Donini Cristina3,Johnstone Hilary4,Langdon Grant5,Wiesner Lubbe1ORCID,Allen Elizabeth12,Duparc Stephan3ORCID,Chalon Stephan3,McCarthy James S.6,Lorch Ulrike7,Chibale Kelly8,Möhrle Jörg3ORCID,Barnes Karen I.12ORCID

Affiliation:

1. Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

2. UCT MRC Collaborating Centre for Optimising Antimalarial Therapy, University of Cape Town, Cape Town, South Africa

3. Medicines for Malaria Venture, Geneva, Switzerland

4. HJ-Clinical Trial Consultancy, George, South Africa

5. PTx Solutions Limited, London, United Kingdom

6. QIMR Berghofer Medical Research Institute, Brisbane, Australia

7. Richmond Pharmacology, London, United Kingdom

8. Drug Discovery and Development Centre (H3D) and South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Cape Town, South Africa

Abstract

MMV390048 is a novel antimalarial compound that inhibits Plasmodium phosphatidylinositol-4-kinase. The safety, tolerability, pharmacokinetic profile, and antimalarial activity of MMV390048 were determined in healthy volunteers in three separate studies. A first-in-human, double-blind, randomized, placebo-controlled, single-ascending-dose study was performed. Additionally, a volunteer infection study investigated the antimalarial activity of MMV390048 using the Plasmodium falciparum induced blood-stage malaria (IBSM) model.

Funder

Technology Innovation Agency of the South African Department of Science and Technology

Medicines for Malaria Venture

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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