Pyronaridine-artesunate With Low Dose Primaquine for Preventing P. Falciparum Transmission (NECTAR1)

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 3; Phase 2

Conditions: Malaria,Falciparum

Treatments: Drug: Pyronaridine Tetraphosphate/Artesunate; Drug: Primaquine Diphosphate; Drug: Dihydroartemisinin/Piperaquine

Study type: Interventional

Funder types: Other

Identifiers

NCT04049916

17507

INV-002098 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full description

Protocol will be shared on request

Enrollment: 100 patients

Sex: All

Ages: 5 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 4 patient groups

Pyronaridine-artesunate (PA)

Active Comparator group

Description:

Subjects will receive pyronaridine-artesunate (PA) once daily for 3 days.

Treatment:

Drug: Pyronaridine Tetraphosphate/Artesunate

PA with single low dose primaquine (PQ)

Experimental group

Description:

Subjects will receive pyronaridine-artesunate (PA) once daily for 3 days, and a low dose of primaquine (PQ) on the first dat of treatment. PQ dose is at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.

Treatment:

Drug: Primaquine Diphosphate

Drug: Pyronaridine Tetraphosphate/Artesunate

Dihydroartemisinin-piperaquine (DP)

Active Comparator group

Description:

Subjects will receive dihydroartemisinin-piperaquine (DP) once daily for 3 days.

Treatment:

Drug: Dihydroartemisinin/Piperaquine

DP with single low dose primaquine (PQ)

Active Comparator group

Description:

Subjects will receive dihydroartemisinin-piperaquine (DP) once daily for 3 days., and a low dose of primaquine (PQ) on the first dat of treatment. PQ dose is at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.

Treatment:

Drug: Dihydroartemisinin/Piperaquine

Drug: Primaquine Diphosphate