Assessing the tolerability of a potentially safer radical curative regimen of primaquine in healthy volunteers with glucose 6 phosphate dehydrogenase deficiency in Thailand
- Conditions
- MalariaPrimaquine radical cureglucose 6 phosphate dehydrogenase deficiency
- Registration Number
- TCTR20170830002
- Lead Sponsor
- niversity of Oxford
- Brief Summary
In Part 1, haemoglobin concentrations fell by a median of 3.7 g/dL (-2.1 to -5.9; relative fall of -26% [range: -15 to -40%]). Primaquine doses up to 0.87 mg/kg/day were tolerated subsequently without clinically significant further falls in haemoglobin. In Part 2, the median haemoglobin fall was 1.7 g/dL (range -0.9 to -4.1; relative fall of -12% [range: -7 to -30%]). The ascending dose primaquine regimens gave 7 times more drug but resulted in double the haemoglobin fall.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Male
- Target Recruitment
- 24
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method