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

NCT ID: NCT04049916

Last Updated: 2020-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-12
• Study Completion Date: 2020-01-07

Brief Summary

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.

Detailed Description

Protocol will be shared on request

Conditions

Malaria,Falciparum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Pyronaridine-artesunate (PA)

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

Group Type: ACTIVE_COMPARATOR

Pyronaridine Tetraphosphate/Artesunate

Intervention Type: DRUG

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.

PA with single low dose primaquine (PQ)

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.

Group Type: EXPERIMENTAL

Pyronaridine Tetraphosphate/Artesunate

Intervention Type: DRUG

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.

Primaquine Diphosphate

Intervention Type: DRUG

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.

Dihydroartemisinin-piperaquine (DP)

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

Group Type: ACTIVE_COMPARATOR

Dihydroartemisinin/Piperaquine

Intervention Type: DRUG

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

DP with single low dose primaquine (PQ)

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.

Group Type: ACTIVE_COMPARATOR

Dihydroartemisinin/Piperaquine

Intervention Type: DRUG

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

Primaquine Diphosphate

Intervention Type: DRUG

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.

Interventions

Pyronaridine Tetraphosphate/Artesunate

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.

Intervention Type: DRUG

Dihydroartemisinin/Piperaquine

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

Intervention Type: DRUG

Primaquine Diphosphate

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.

Intervention Type: DRUG

Other Intervention Names

Pyramax; Euartesim; Primaquine

Eligibility Criteria

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

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Malaria Research and Training Center, Bamako, Mali

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Malaria Research and Training Centre

Bamako, , Mali

Radboud university medical center

Nijmegen, , Netherlands

Countries

Mali; Netherlands

References

Stone W, Mahamar A, Sanogo K, Sinaba Y, Niambele SM, Sacko A, Keita S, Youssouf A, Diallo M, Soumare HM, Kaur H, Lanke K, Ter Heine R, Bradley J, Issiaka D, Diawara H, Traore SF, Bousema T, Drakeley C, Dicko A. Pyronaridine-artesunate or dihydroartemisinin-piperaquine combined with single low-dose primaquine to prevent Plasmodium falciparum malaria transmission in Ouelessebougou, Mali: a four-arm, single-blind, phase 2/3, randomised trial. Lancet Microbe. 2022 Jan;3(1):e41-e51. doi: 10.1016/S2666-5247(21)00192-0.

Reference Type: DERIVED

PMID: 35028628 (View on PubMed)

Other Identifiers

INV-002098

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

17507

Identifier Type: -

Identifier Source: org_study_id