Single Low-dose Primaquine Efficacy and Safety.

NCT03352843 | Completed Phase 4 DMC

• 1 other identifier: TMA2016CDF-1555
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 1

Brief 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

Malaria

Outcome Measures

Primary Outcomes (1)

• Safety of single low-dose primaquine.

  Proportion of participants with adverse and or serious adverse events between days 0 and 28 of follow up following treatment with a single low-dose primaquine in individuals with reduced/null compared to those with normal/increased CYP450 2D6 isoenzyme activity.

  6 months after the start of recruitment

Secondary Outcomes (2)

• Sterilization of gametocytes

  6 months after the start of recruitment

• Gametocytes carriage on day 7

  12 months after the start of recruitment

Study Arms (1)

Single arm

EXPERIMENTAL

Drug: Primaquine

Interventions

Primaquine DRUG

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.

Single arm

Eligibility Criteria

• Age: 1 Year - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age from 1 to 10 years
• Weight ≥ 10 kg
• Body temperature ≥ 37.5°C or history of fever in the last 24 hours
• Microscopy confirmed P. falciparum mono-infection
• Parasitemia level of 2000 - 200000/µL
• Ability to swallow oral medication
• Ability and willingness to abide by the study protocol and the stipulated follow up visits
• Written proxy informed consent from a parent/guardian.

You may not qualify if:

• Evidence of severe malaria or danger signs
• Known allergy to trial medicines
• Reported antimalarial intake ≤ 2 weeks
• Hemoglobin \< 5 g/dL
• Blood transfusion within last 90 days
• Febrile condition other than malaria
• Known underlying chronic or severe disease

Sponsors & Collaborators

• Tropical Pesticides Research Institute, Tanzania: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (1)

Tropical Pesticides Research Institute (TPRI)

Arusha, Tanzania

Location

Related Publications (1)

• Mwaiswelo RO, Ngasala B, Msolo D, Kweka E, Mmbando BP, Martensson A. A single low dose of primaquine is safe and sufficient to reduce transmission of Plasmodium falciparum gametocytes regardless of cytochrome P450 2D6 enzyme activity in Bagamoyo district, Tanzania. Malar J. 2022 Mar 12;21(1):84. doi: 10.1186/s12936-022-04100-1.

  PMID: 35279143 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Primaquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Richard O Mwaiswelo, PhD

  Tropical Pesticides Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Scientist

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 24, 2017
• Study Start: June 11, 2019
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2020
• Last Updated: February 24, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

TA (1)