Assessing the tolerability of a single dose of 45 mg of primaquine as an extension to assessing a potentially safer radical curative regimen of primaquine in healthy volunteers with glucose-6-phosphate dehydrogenase deficiency in Thailand

Phase 1

Completed

• Conditions: Malariaglucose 6 phosphate dehydrogenase deficiency; glucose 6 phosphate dehydrogenase deficiency; Primaquine; Malaria

• Registration Number: TCTR20220317004
• 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

Study Timeline

• Study Start: 2022-03-17
• Study Completion: 2022-09-29
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Male
• Target Recruitment: 16

Inclusion Criteria

1. Male aged between the age of 18 and 65 years
2. Hb more than and/or equal to 11 g/dL
3. Healthy as judged by the history taking and examining physician
4. Written informed consent provided by the volunteer. Witnessed consent is required, if the individual cannot read or write.

Exclusion Criteria

1. Known to have any clinically significant disease or to have a clinically significant disease or disorder at this screening time
2. Received a blood transfusion in the past 3 months
3. Donated more than 300 mL of whole blood within the previous 3 months
4. Taking or taken within the past 3 weeks any drug known to cause haemolysis in G6PD deficiency
5. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) > 1.5 times the upper limit of normal (ULN)
6. A serum creatinine (Scr) above the upper limit of normal (> 1.2 mg/dL) and an eGFR < 70 mL/min/1.73 m2 *
7. Conjugated bilirubin > 1.5 x ULN
8. Unconjugated bilirubin > 1.5 x ULN
9. Methaemoglobin (MetHb) level > 5% determined by oximetry
10. Have taken part in research involving an investigational drug within the past 8 weeks.
11.Subject who is likely to be unable to follow with the study procedures

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Assess the haematological effect of a single dose of primaquine in healthy G6PD deficient hemizygous males Day 0 to Day 14 Haemoglobin concentrations and reticulocyte counts over time

Secondary Outcome Measures

Name	Time	Method
Assess tolerability 1 year Adverse events,Document the disposition of primaquine and carboxyprimaquine Day 0 over 24 hour Concentrations of primaquine and carboxyprimaquine ,Define the relationships between primaquine pharmacokinetics and fall in haemoglobin and rise in reticulocyte counts Day 0 to Day 14 Haemoglobin and reticulocyte profiles derived from a pharmacokinetic pharmacodynamic model,Attempt to identify primaquine's oxidative metabolites in blood and urine Day 0 to Day 14 Measure 2, 3, 4 & 5 hydroxyprimaquine and 5, 6-orthoquinone in whole blood, plasma, red cells and urine.