Pyronaridine-artesunate With Low Dose Primaquine for Preventing P. Falciparum Transmission

London School of Hygiene and Tropical Medicine100 enrolled

Overview

The purpose of this study is to assess the gametocytocidal and transmission reducing activity of pyronaridine-artesunate (PA) and dihydroartemisinin-piperaquine (DP) with and without a single low dose of primaquine (PQ; 0.25mg/kg). Outcome measures will include infectivity at 2 and 7 days after treatment, the duration of infectivity in the artemisinin combination therapy (ACT) only arms, and the production and detectability of histidine rich protein II.

Protocol will be shared on request

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

100

Conditions

Malaria,Falciparum

Interventions

Pyronaridine Tetraphosphate/ArtesunateDRUG

Adults: Tablets containing 180 mg pyronaridine-tetraphosphate/60mg artesunate (Pyramax, Shin Poong Pharmaceutical Co.), administered according to weight. Children: Granules containing 60 mg pyronaridine-tetraphosphate/20mg artesunate, administered according to weight.

Dihydroartemisinin/PiperaquineDRUG

Tablets containing 40 mg dihydroartemisinin/320 mg piperaquine tablets (Eurartesim, Sigma Tau), administered according to weight.

Primaquine DiphosphateDRUG

Extemporaneous preparation of 1mg/mL primaquine phosphate solution, from tablets containing 30mg primaquine (A-PQ 30®, ACE pharmaceuticals, NL) dissolved in 30mL water with a non-interacting fruit-flavoured syrup. Solution will be given at 0.25mg/kg.

Eligibility

Sex: ALLMin age: 5 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 5 years and ≤ 50 years * Absence of symptomatic falciparum malaria, defined by fever on enrolment * Presence of ≥16 gametocytes/µL (i.e. ≥1 gametocytes recorded in the thick film against 500 white blood cells) * No allergies to study drugs * Use of antimalarial drugs over the past 7 days (as reported by the participant) * Hemoglobin ≥ 9.5 g/dL * Individuals weighing \>\< 80 kg * No evidence of severe or chronic disease * Written, informed consent Exclusion Criteria: * Age \< 5 years or \> 50 years * Pregnancy * Previous reaction to study drugs/known allergy to study drugs * Signs of severe malaria * Taking drugs which may be metabolized by cytochrome enzyme CYP2D6 (e.g., flecainide, metoprolol, imipramine, amitriptyline, clomipramine) * Blood transfusion within the last 90 days * Patients with clinical signs or symptoms of hepatic injury (such as nausea and/or abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child-Pugh stage B or C). * Patients with clinical signs or symptoms of renal impairment or known renal impairment * Family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to prolong the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease. * Taking drugs that are known to influence cardiac function and to prolong QTc interval, such as class IA and III: neuroleptics, antidepressant agents, certain antibiotics including some agents of the following classes - macrolides, fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics (terfenadine, astemizole) and cisapride. * Consent not given

Locations (2)

Malaria Research and Training Centre

Bamako, Mali

Radboud university medical center

Nijmegen, Netherlands

Outcomes

Primary Outcomes

Change in mosquito infectivity assessed through membrane feeding assays (day 2)

The proportion of mosquitoes infected, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 2 post feed, compared to baseline

Time frame: 2 days (day 0 & 2)

Secondary Outcomes

Change in mosquito infectivity assessed through membrane feeding assays (day 7)

The proportion of mosquitoes infected, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 7 post feed, compared to baseline

Time frame: 2 days (day 0 & 7)

Mosquito infectivity assessed through membrane feeding assays - inter arm

Mosquito infection prevalence and density, assessed through membrane feeding and measured as oocyst prevalence/density in mosquitoes dissected on day 2 and 7 post feed, compared between study arms

Time frame: 3 days (day 0, 2 & 7)

Duration of infectivity

Non PQ arms only: Duration of infectivity will be determined from measures of mosquito infection prevalence, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 0, 2, 7, 10 and 14 post treatment, and then weekly until 2 sequential negative feeds or until day 49.

Time frame: 5-10 days (as described)

Area under the curve (AUC) of infectivity/time

Non PQ arms only: AUC will be determined from measures of mosquito infection prevalence and density, assessed through membrane feeding and measured as oocyst prevalence/density in mosquitoes dissected on day 0, 2, 7, 10 and 14 post treatment, and then weekly until 2 sequential negative feeds or until day 49.

Time frame: 5-10 days (as described)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.