NCT05938608

A Study to Assess the Availability of Oral Primaquine and Its Inert Metabolite, Carboxyprimaquine, in the Body

An Open-Label Pharmacokinetic Study to Evaluate the Bioavailability of Oral Primaquine and the Pharmacokinetics of Carboxyprimaquine in Healthy Adult Subjects

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

An open-label pharmacokinetic study. This study will enroll 20 healthy adult subjects (10 males and 10 females aged 18-60 years) at the Clinical Therapeutics Unit or inpatient ward, Faculty of Tropical Medicine, Mahidol University, Thailand. The investigator propose to conduct a definitive bioavailability and pharmacokinetic study in healthy adult volunteers, both male and female, with normal CYP2D6 genotypes to assess oral primaquine bioavailability by the administration of intravenous and oral primaquine on different days and calculate the proportion of drug converted to its inactive metabolite, carboxyprimaquine, in order to estimate the proportion of its active metabolites. The intravenous injection of the known amount of carboxyprimaquine will allow the calculation of carboxyprimaquine's volume of distribution.

Detailed description

This study will enroll 20 healthy adult subjects (10 males and 10 females aged 18-60 years). Subjects will be admitted in the hospital and will receive 3 regimens of primaquine and its metabolite as described below. Every subject will have 1 screening and 3 admissions in the hospital. Regimen 1: Primaquine 15 mg base orally once Regimen 2: Primaquine 7.5 mg base in normal saline 500 mL infused over 30 minutes intravenously Regimen 3: Carboxyprimaquine 7.93 mg base in normal saline 500 mL infused over 30 minutes intravenously Washout period will be at least 2 weeks between each regimen. The pharmacokinetic blood samples, 2 mL, will be collected at the scheduled times relative to when the subject was dosed for each regimens as follow. Regimen 1: 16 blood samples collected from day 1 at 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose, day 1 at 24 hours post-dose, day 2 at 48 hours post-dose and only 1 sampling at any time on day 3, 5 and 7. Regimen 2 and 3: 17 blood samples collected from day 1 at 0 (pre-dose), 0.25 (during), 0.5 (immediately after), 0.75, 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose, day 1 at 24 hours post-dose, day 2 at 48 hours post-dose and only 1 sampling at any time on day 3, 5 and 7. Plasma samples will be assayed by a validated Liquid Chromatography-Mass Spectrometer (LCMS/MS) method developed at Mahidol Oxford Tropical Medicine Research Unit (MORU), which is specific for the determination of primaquine and its metabolite, carboxyprimaquine. Individual concentration-time data will be evaluated using a non-compartmental analysis approach. Pharmacokinetic parameters (i.e. Area under the concentration-time curve (AUC0-LAST, AUC0-∞), Maximum concentration (CMAX), Time to maximum concentration (TMAX), elimination clearance (CL/F), apparent volume of distribution (VD/F), and terminal elimination half-life (t1/2)) will be described using means (SD or 95% CI) and medians (range) as appropriate. Bioavailability of oral primaquine will be calculate based on the dose-normalised exposure (AUC0-LAST and AUC0-∞) to primaquine after oral and intravenous administration.

Conditions

• Healthy
• Pharmacokinetic

Interventions

Type	Name	Description
DRUG	Regimen 1 (Oral primaquine)	Primaquine 15 mg base orally once
DRUG	Regimen 2 (IV primaquine phosphate)	Primaquine 7.5 mg base in normal saline 500 mL infused over 30 minutes intravenously
DRUG	Regimen 3 (IV carboxyprimaquine)	Carboxyprimaquine 7.93 mg base in normal saline 500 mL infused over 30 minutes intravenously

Timeline

• Start date: 2024-03-01
• Primary completion: 2025-03-01
• Completion: 2025-03-01
• First posted: 2023-07-10
• Last updated: 2024-05-06

Locations

1 site across 1 country: Thailand