Trial reportBritish journal of clinical pharmacology2015
Evaluation of the QT effect of a combination of piperaquine and a novel anti-malarial drug candidate OZ439, for the treatment of uncomplicated malaria.
Trial report in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Factors affecting the electrocardiographic QT interval in malaria: A systematic review and meta-analysis of individual patient data.PLoS medicine · 2020Pooled it
- The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: a systematic review.BMC medicine · 2018Pooled it
- Concentration-Response Analysis of the Combination of Pyronaridine and Piperaquine on Corrected QT Interval From a Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults of African Sub-Saharan Origin.Clinical and translational science · 2025Trial
- Trial
- Pharmacokinetics-Pharmacodynamics of High-Dose Ivermectin with Dihydroartemisinin-Piperaquine on Mosquitocidal Activity and QT-Prolongation (IVERMAL).Clinical pharmacology and therapeutics · 2019Trial
- Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers.British journal of clinical pharmacology · 2017Trial
- Trial
- Piperaquine Population Pharmacokinetics and Cardiac Safety in Cambodia.Antimicrobial agents and chemotherapy · 2017Trial
- Ex vivo piperaquine resistance developed rapidly in Plasmodium falciparum isolates in northern Cambodia compared to Thailand.Malaria journal · 2016Trial
- Piperaquine Monotherapy of Drug-Susceptible Plasmodium falciparum Infection Results in Rapid Clearance of Parasitemia but Is Followed by the Appearance of Gametocytemia.The Journal of infectious diseases · 2016Trial
- Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label phase 2 trial.The Lancet. Infectious diseases · 2016Trial
- Diagnosis and management of malaria in the intensive care unit.Journal of intensive medicine · 2024Review
- Drugs for Intermittent Preventive Treatment of Malaria in Pregnancy: Current Knowledge and Way Forward.Tropical medicine and infectious disease · 2022Review
- Pooled Multicenter Analysis of Cardiovascular Safety and Population Pharmacokinetic Properties of Piperaquine in African Patients with Uncomplicated Falciparum Malaria.Antimicrobial agents and chemotherapy · 2020Article
- Application of Low-Frequency Raman Scattering Spectroscopy to Probe in Situ Drug Solubilization in Milk during Digestion.The journal of physical chemistry letters · 2019Article
- Impact of Ferroquine on the Solubilization of Artefenomel (OZ439) during in Vitro Lipolysis in Milk and Implications for Oral Combination Therapy for Malaria.Molecular pharmaceutics · 2019Article
- Evaluation of the effects on the QT-interval of 4 artemisinin-based combination therapies with a correction-free and heart rate-free method.Scientific reports · 2019Article
- Comparison of the Pharmacokinetics and Ex Vivo Antimalarial Activities of Artesunate-Amodiaquine and Artemisinin-Piperaquine in Healthy Volunteers for Preselection Malaria Therapy.The American journal of tropical medicine and hygiene · 2018Article
- Drugs in Development for Malaria.Drugs · 2018Review
- Challenges to replace ACT as first-line drug.Malaria journal · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe aim was to investigate the QT effect of a single dose combination regimen of piperaquine phosphate (PQP) and a novel aromatic trioxolane, OZ439, for malaria treatment.
methodsExposure-response (ER) analysis was performed on data from a placebo-controlled, single dose, study with OZ439 and PQP. Fifty-nine healthy subjects aged 18 to 55 years received OZ439 alone or placebo in a first period, followed by OZ439 plus PQP or matching placebos in period 2. OZ439 and PQP doses ranged from 100-800 mg and 160-1440 mg, respectively. Twelve-lead ECG tracings and PK samples were collected serially pre- and post-dosing.
resultsA significant relation between plasma concentrations and placebo-corrected change from baseline QTc F (ΔΔQTc F) was demonstrated for piperaquine, but not for OZ439, with a mean slope of 0.047 ms per ng ml(-1) (90% CI 0.038, 0.057). Using an ER model that accounts for plasma concentrations of both piperaquine and OZ439, a largest mean QTc F effect of 14 ms (90% CI 10, 18 ms) and 18 ms (90% CI 14, 22 ms) was predicted at expected plasma concentrations of a single dose 800 mg OZ439 combined with PQP 960 mg (188 ng ml(-1) ) and 1440 mg (281 ng ml(-1) ), respectively, administered in the fasted state.
conclusionsPiperaquine prolongs the QTc interval in a concentration-dependent way. A single dose regimen combining 800 mg OZ439 with 960 mg or 1440 mg PQP is expected to result in lower peak piperaquine plasma concentrations compared with available 3 day PQP-artemisinin combinations and can therefore be predicted to cause less QTc prolongation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.