Pharmacokinetics and Pharmacodynamics of the Gametocytocidal and Post-treatment Chemoprotective Effects of Antimalarials

NCT04009343 | Active Not Recruiting Phase 2

• 1 other identifier: IRB00007663
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 1

Brief Summary

Single-center phase II/III clinical investigation of the pharmacokinetics and pharmacodynamics of artemether-lumefantrine and dihydroartemisinin-piperaquine for gametocyte clearance and post-treatment chemoprotection in Zambian children with uncomplicated falciparum malaria.

Conditions

Uncomplicated Falciparum Malaria

Outcome Measures

Primary Outcomes (3)

• Treatment outcome

  Defined according to World Health Organization (WHO) classification as adequate clinical and parasitological response, early treatment failure, late clinical failure, or late parasitological failure corrected by genotyping to distinguish reinfection from recrudescent infection.

  9 weeks

• Area-under-the-curve (AUC) of the gametocyte concentration-time curve

  Primary gametocyte-related pharmacodynamic (PD) endpoint of the study

  72 hours

• Incidence of reinfection during the 9-week follow-up period

  Primary measure of the post-treatment chemoprotective effect of the drugs

  9 weeks

Secondary Outcomes (5)

• Elimination half-life of the gametocyte concentration-time curve

  72 hours up to 9 weeks for those with persistent gametocytemia

• Change over time of the gametocyte sex ratio (female:male)

  72 hours up to 9 weeks for those with persistent, emergent, or recurrent gametocytes

• Elimination half-life of the asexual parasite concentration-time curve

  72 hours

• Allele frequency of genetic markers of parasite drug resistance in initial vs. recurrent parasites and fast vs. slow clearing parasites

  9 weeks

• Incidence of treatment-emergent adverse events (safety and tolerability)

  9 weeks

Other Outcomes (6)

• AUC of the plasma concentration-time curve

  72 hours (artemisinin derivatives) and 9 weeks (long-acting companions)

• Peak plasma concentration (Cmax) of study drugs and metabolites

  72 hours (artemisinin derivatives) and 9 weeks (long-acting companions)

• Oral clearance (Cl/F) for all drug analytes

  72 hours (artemisinin derivatives) and 9 weeks (long-acting companions)

Study Arms (2)

Artemether-lumefantrine

ACTIVE COMPARATOR

Standard 6-dose regimen

Drug: Artemether-lumefantrine

Dihydroartemisinin-piperaquine

EXPERIMENTAL

Standard 3-dose regimen

Drug: Dihydroartemisinin-piperaquine

Interventions

Artemether-lumefantrine DRUG

Children will receive artemether-lumefantrine (20/120 mg) dosed according to weight (5 to \<15 kg: 1 tablet, 15 to \<25 kg: 2 tablets) at 0, 8, 24, 36, 48 and 60 hours. Medications will be administered according to the manufacturer's instructions.

Also known as: Coartem®

Artemether-lumefantrine

Dihydroartemisinin-piperaquine DRUG

Children will receive dihydroartemisinin-piperaquine (40/320 mg) dosed according to weight (5 to \<8 kg: 1/2 tablet, 8 to \<11 kg: 3/4 tablet, 11 to \<17 kg: 1 tablet, 17 to \<25 kg: 1 1/2 tablets) at 0, 24, and 48 hours. Medications will be administered according to the manufacturer's instructions.

Also known as: D-Artepp®

Dihydroartemisinin-piperaquine

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Weight ≥10 kg
• Any indication for malaria diagnostic testing as determined by a treating provider (e.g., fever or history of fever)
• P. falciparum parasitemia (by microscopy) of any density not meeting criteria for severe malaria
• Ability to swallow oral medication
• Ability and willingness of parents or guardians to comply with study protocol for the duration of the study and to comply with the study follow-up visit schedule
• Residence within hospital catchment area
• Signed informed consent obtained from a legal representative of the participant

You may not qualify if:

• Complicated or severe falciparum malaria as defined by WHO criteria
• Hemoglobin concentration \< 7 g/dL
• Use of any drug with antimalarial activity within the prior 4 weeks
• History of hypersensitivity reaction or intolerance to AL or DP
• Co-infection with Plasmodium spp. other than P. falciparum as determined by microscopy
• Confirmed or suspected concurrent acute infection other than malaria (e.g. measles, acute lower respiratory tract infection)
• Current therapy with QT interval-prolonging agents
• Family history of sudden cardiac death or personal history of cardiac disease
• Residence outside the study area, or plan to leave the study area
• Residence in foster care or otherwise under government supervision
• Previous enrollment in the study, or enrollment in any other investigational drug trial during the previous 30 days
• Presence of any other condition or abnormality that in the opinion of the investigator would compromise the safety of the participant or the quality of the data

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• Tropical Diseases Research Centre: collaborator

Study Sites (1)

Tropical Diseases Research Centre

Ndola, Copperbelt, Zambia

Location

MeSH Terms

Interventions

Artemether, Lumefantrine Drug Combination

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• William J Moss, MD MPH

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants and clinical trial nurses and pharmacists will be aware of the treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2019
• First Posted: July 5, 2019
• Study Start: June 19, 2019
• Primary Completion: August 24, 2020
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

ZA (1)