Malaria Primaquine radical cure glucose 6 phosphate dehydrogenase deficiency
Conditions
Interventions
Primaquine daily dose starting with 1) 7.5 mg 5 days,
2) 15 mg 5 days,
3) 22.5 mg 5 days,
and 4) 30 mg 5 days
Experimental Drug
Sponsors
University of Oxford
Eligibility
Sex/Gender
Male
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Male aged between the age of 18 and 65 years 2. Healthy as judged by the examining physician 3. Hb >= 11 g/dL 4. G6PD activity < 30% of the population median of 11.5 U/g Hb 5. Written informed consent provided by the volunteer. Witnessed consent is required, if the individual cannot read or write. 6. Willing to participate in this study
Exclusion criteria
Exclusion criteria: 1. BMI >= 35 2. G6PD Mediterranean variant 3. Known to have any clinically significant disease or to have a clinically significant disease or disorder discovered by the investigator requiring treatment or further investigation 4. Malaria or other febrile illness (e.g. viral hepatitis, typhoid fever) in the previous month that could result in haemolysis in G6PDd 5. Positive blood film for malaria (asexual or sexual parasites) 6. History of haemolysis not related to primaquine in the past 8 weeks 7. Being rhesus negative 8. Received a blood transfusion in the past 3 months 9. Subject who has donated more than 300 mL of whole blood within the previous 3 months 10. Taking or taken within the past 3 weeks any herbal medicine 11. Taking or taken within the past 3 weeks any drug known to cause haemolysis in G6PD deficiency 12. AST and ALT and LDH > 1.5 times the upper limit of normal (ULN) 13. A serum creatinine above the upper limit of normal (>1.2 mg/dL) and an eGFR < 70 mL/min/1.73m2 (the eGFR for males is calculated based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation: 13.1 eGFR = 141 x min(Scr/k, 1)power alpha x max(Scr/k, 1)power -1.209 x 0.993 power Age 13.2 where Scr is serum creatinine, k = 0.9 for males, alpha = -0.411 for males 13.3 min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1) 13.4 the eGFR can be calculated online: https://qxmd.com/calculate/calculator_251/egfr-using-ckd-epi) 14. Urine analysis (UA) reveals the chronic renal disease defined as RBC >= 5 and/or Proteinuria; trace or above 15. Conjugated bilirubin > 1.5 x ULN 16. Unconjugated bilirubin > 1.5 x ULN 17. Methaemoglobin level > 5% determined by oximetry 18. Allergic to primaquine 19. Have taken part in research involving an investigational drug within the past 8 weeks. 20. Subject who, in the opinion of the investigator, have a risk of non-compliance with study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety and tolerability of a 20 day, ascending dose of primaquine in healthy volunteers with G6PD de 1 year The proportion of subjects able to complete the study without having their primaquine stopped | — |
Secondary
| Measure | Time frame |
|---|---|
| To determine markers of haemolysis over time 1 year Validation of within-host model predictions of heamoglobin and reticulocyte dynamics over time,To determine markers of haemolysis over time 1 year Factors affecting Hb changes over time ,To determine markers of haemolysis over time 1 year Time to nadir Hb concentration,To determine markers of haemolysis over time 1 year Nadir Hb concentration,To determine markers of haemolysis over time 1 year absolute and fractional fall in Hb on day of nadir Hb vs. baseline,Pharmacokinetic (PK) properties of primaquine (PQ) and carboxyPQ 1 year Pharmacokinetic (PK) properties of primaquine (PQ) and carboxyPQ,G6PD enzyme activity and genotype and the presence of other inherited blood disorders 1 year G6PD phenotype,G6PD enzyme activity and genotype and the presence of other inherited blood disorders 1 year G6PD genotype,Rates of acute kidney injury 1 year incidence of grade 3 & 4 clinical adverse events,Rates of acute kidney injury 1 year incidence of laboratory adverse events,To determine markers of haemolysis over time 1 year changes in biochemical markers of haemolysis over time,Primaquine metabolite activity on in vitro cultured Plasmodium gametocytes 1 year Primaquine metabolite | — |
Countries
Thailand
Contacts
Public ContactNick White
Mahidol Oxford Tropical Medicine Research unit
Outcome results
None listed