Single Low-dose Primaquine Efficacy and Safety.

Malaria Clinical Trial

— ESSLDPQP4502D6  

Official title:

Single Low-dose Primaquine Efficacy and Safety for Treatment of Uncomplicated Plasmodium Falciparum Malaria Based on Cytochrome P450 2D6 Activity in Bagamoyo District, Tanzania.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03352843
• Other study ID #: TMA2016CDF-1555
• Status: Completed
• Phase: Phase 4
• Start date: June 11, 2019
• Est. completion date: February 28, 2020

Study information

• Verified date: February 2023
• Source: Tropical Pesticides Research Institute, Tanzania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: February 28, 2020
• Est. primary completion date: February 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 10 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Malaria

Intervention

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.

Locations

Country	Name	City	State
Tanzania	Tropical Pesticides Research Institute (TPRI)	Arusha

Sponsors (2)

Lead Sponsor	Collaborator
Tropical Pesticides Research Institute, Tanzania	European and Developing Countries Clinical Trials Partnership (EDCTP)

Country where clinical trial is conducted

Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Sterilization of gametocytes	Proportion of participants with infected mosquitoes following membrane feeding experiment on day 7.	6 months after the start of recruitment
Secondary	Gametocytes carriage on day 7	Proportion of participants with gametocytes carriage measured by QT-NASBA on day 7	12 months after the start of recruitment