MedTrace Logo

Single Low-dose Primaquine Efficacy and Safety.

NCT03352843 · Status: COMPLETED · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 157

Last updated 2023-02-24

No results posted yet for this study

Summary

Background: The World Health Organization has recommended addition of a 0.25 mg/kg single-dose primaquine (PQ) to standard artemisinin-based combination therapy (ACT) for elimination of malaria in low transmission-settings and for containment in areas threatened by artemisinin resistance. However, PQ metabolism is dependent on a highly polymorphic cytochrome P450 (CYP) 2D6 isoenzyme which probably compromises the drugs' safety and efficacy, particularly in individuals with reduced isoenzyme activity. This trial therefore, aims to assess the safety and efficacy of 0.25 mg/kg single-dose PQ when added to standard artemether-lumefantrine regimen for clearance and sterilization of Plasmodium falciparum gametocytes in patients with CYP450 2D6 reduced/null activity as compared to those with normal/increased enzyme activity.

Methods: On hundred and fifty-five children aged between 1 and 10 years and with uncomplicated P. falciparum malaria will be enrolled, treated with standard artemether-lumefantrine regimen plus a 0.25 mg/kg single-dose of PQ and then followed up on days 0, 1, 2, 3, 7, 14, 21 and 28 for clinical and laboratory assessment. Primaquine will be administered together with the first dose of artemether-lumefantrine. Safety assessment will be performed using the Primaquine Roll Out Monitoring Pharmacovigilance Tool (PROMPT). Gametocytes will be detected and quantified by microscopy and Pfs25 mRNA quantitative nucleic acid sequence based amplification (QT-NASBA) on days 0 and 7. For a subset of 100 participants, post-treatment infectiousness will be assessed by mosquito feeding assays on day 7. The CYP2D6 status will be determined using a polymerase chain reaction (PCR) followed by a restriction fragment length polymorphism (RFLP). The primary outcome will be the safety of single low-dose primaquine in patients with CYP2D6 reduced/null compared to those with normal/increased activity.

Expected outcomes: The findings will provide the much-needed information on the safety and efficacy of single low-dose primaquine for clearance and sterilization of P. falciparum gametocytes in individuals with reduced/null compared to those with normal/increased CYP450 2D6 isoenzyme activity prior to the implementation of the treatment policy particularly in Africa.

Conditions

Interventions

DRUG

Primaquine

All patients will be administered with a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen, and then followed-up for 28 days for clinical and laboratory assessment to assess safety and efficacy.

Sponsors & Collaborators

  • European and Developing Countries Clinical Trials Partnership (EDCTP)

    collaborator OTHER_GOV

  • Tropical Pesticides Research Institute, Tanzania

    lead OTHER_GOV

Principal Investigators

  • Richard O Mwaiswelo, PhD · Tropical Pesticides Research Institute

Study Design

Allocation
NA
Purpose
PREVENTION
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
1 Year
Max Age
10 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-06-11
Primary Completion
2020-02-28
Completion
2020-02-28

Countries

  • Tanzania

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03352843 on ClinicalTrials.gov