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

NCT05938608 | Withdrawn Phase 1

• 1 other identifier: MAL22006
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy; Pharmacokinetic

Keywords

Primaquine; Carboxyprimaquine

Outcome Measures

Primary Outcomes (8)

• Area under the concentration-time curve (AUC0-∞) of oral and intravenous primaquine.

  Approximately 3 months

• Area under the concentration-time curve (AUC0-last) of oral and intravenous primaquine.

  Approximately 3 months

• Area under the concentration-time curve (AUC0-∞) of primaquine and carboxyprimaquine

  Approximately 3 months

• Area under the concentration-time curve (AUC0-last) of primaquine and carboxyprimaquine

  Approximately 3 months

• Maximum concentration (Cmax) of primaquine and carboxyprimaquine

  Approximately 3 months

• Elimination clearance (CL/F) of primaquine and carboxyprimaquine

  Approximately 3 months

• Terminal elimination half-life (t1/2) of primaquine and carboxyprimaquine

  Approximately 3 months

• Apparent volume of distribution (Vd) of primaquine and carboxyprimaquine

  Approximately 3 months

Secondary Outcomes (1)

• The characteristics of genetic polymorphisms of potential enzymes involved in drug metabolism in the case of unusual metabolizer

  Approximately 3 months

Study Arms (1)

Regimen 1 (Oral primaquine), 2(IV primaquine phosphate), 3(IV carboxyprimaquine)

EXPERIMENTAL

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

Drug: Regimen 1 (Oral primaquine); Drug: Regimen 2 (IV primaquine phosphate); Drug: Regimen 3 (IV carboxyprimaquine)

Interventions

Regimen 1 (Oral primaquine) DRUG

Primaquine 15 mg base orally once

Regimen 1 (Oral primaquine), 2(IV primaquine phosphate), 3(IV carboxyprimaquine)

Regimen 2 (IV primaquine phosphate) DRUG

Primaquine 7.5 mg base in normal saline 500 mL infused over 30 minutes intravenously

Regimen 1 (Oral primaquine), 2(IV primaquine phosphate), 3(IV carboxyprimaquine)

Regimen 3 (IV carboxyprimaquine) DRUG

Carboxyprimaquine 7.93 mg base in normal saline 500 mL infused over 30 minutes intravenously

Regimen 1 (Oral primaquine), 2(IV primaquine phosphate), 3(IV carboxyprimaquine)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy as judged by a responsible physician with no significant abnormality identified on a medical evaluation including medical history and physical examination.
• Male or female aged between 18 years to 60 years.
• A female is eligible to enter and participate in this study if she is:
• of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy
• postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels \>40 milli-international units per milliliter (mIU/mL) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy
• of childbearing potential, has a negative serum pregnancy test at screening and urine pregnancy test prior to start the study drug in each period, and agrees to abstain from sexual intercourse or use effective contraceptive methods (e.g., intrauterine device, tubal ligation or female barrier method with spermicide except hormonal contraceptive) during the study until completion of the follow-up procedures
• Willingness and ability to comply with the study protocol for the duration of the trial.
• Subject is willing and able to give written informed consent for full participation in the study

You may not qualify if:

• Females who are pregnant, trying to get pregnant, or are lactating.
• Known to have any clinically significant disease or to have a clinically significant disease or disorder at this screening time
• Donated more than 300 mL of whole blood within the previous 3 months
• Non-smokers and non-tobacco user (i.e. having no past history of smoking and tobacco consuming for at least 3 months prior to study)
• Consume alcohol or other alcohol containing products within 48 hours prior to the first dose of study drug and throughout the study
• History or evidence of alcohol or substance abuse or dependence within 6 months before and throughout the study
• Consume grapefruit and grapefruit containing products within 7 days prior to the first dose of study drug and throughout the study
• Use of prescription drugs including but not limited to drugs with antimalarial activities and any drug contraindicated with the investigational drugs e.g. quinacrine, mefloquine or non-prescription drug, including, vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication and for the duration of the trial including follow-up will be prohibited
• Have taken part in research involving an investigational drug within the past 8 weeks
• Use of medications known to have a potentially clinically significant interaction with primaquine
• History of allergy to primaquine
• Hb \< 11 g/dL
• Having malaria infection
• Abnormal CYP2D6 genotype
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency by screening test

Sponsors & Collaborators

• University of Oxford: lead
• Mahidol Oxford Tropical Medicine Research Unit: collaborator
• Mahidol University: collaborator

Study Sites (1)

Faculty of Tropical Medicine, Mahidol University

Bangkok, Thailand

Location

MeSH Terms

Interventions

Primaquine; 8-(3-carboxy-1-methylpropylamino)-6-methoxyquinoline

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Borimas Hanboonkunupakarn, Asst. Prof

  Mahidol Oxford Tropical Medicine Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label pharmacokinetic study in 20 healthy adult subjects. Subjects will be admitted in the hospital and will receive 3 regimens of primaquine and its metabolite. Every subject will have 1 screening and 3 admissions in the hospital.

Study Record Dates

• First Submitted: June 22, 2023
• First Posted: July 10, 2023
• Study Start: March 1, 2024
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: May 6, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Access to study data will be provided following the MORU data sharing policy.

Locations

TH (1)