Trial reportAntimicrobial agents and chemotherapy2015
Evaluating the pharmacodynamic effect of antimalarial drugs in clinical trials by quantitative PCR.
Trial report in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02223871 (A Proof-of-concept Study to Assess the Effect of ACT-451840 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Subjects), which is not on this map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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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.
A Proof-of-concept Study to Assess the Effect of ACT-451840 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Subjects
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Evaluation of a multiphasic parasite clearance profile after treatment of experimental human infection with the investigational anti-malarial M5717 using segmented mixed effect models.Malaria journal · 2023Pooled it
- Trial
- Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection study.The Lancet. Infectious diseases · 2021Trial
- Safety and parasite clearance of artemisinin-resistant Plasmodium falciparum infection: A pilot and a randomised volunteer infection study in Australia.PLoS medicine · 2020Trial
- Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study.The Lancet. Infectious diseases · 2017Trial
- A Phase II pilot trial to evaluate safety and efficacy of ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study.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
- Linking Murine and Human Plasmodium falciparum Challenge Models in a Translational Path for Antimalarial Drug Development.Antimicrobial agents and chemotherapy · 2016Trial
- A roadmap for understanding sulfadoxine-pyrimethamine in malaria chemoprevention.Parasitology · 2025Review
- Advancing liposome technology for innovative strategies against malaria.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Review
- Characterizing the Blood-Stage Antimalarial Activity of Tafenoquine in Healthy Volunteers Experimentally Infected With Plasmodium falciparum.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Antimalarial Activity of Artefenomel Against Asexual Parasites and Transmissible Gametocytes During Experimental Blood-Stage Plasmodium vivax Infection.The Journal of infectious diseases · 2022Article
- Scoping Review of Antimalarial Drug Candidates in Phase I and II Drug Development.Antimicrobial agents and chemotherapy · 2022Article
- Haematological response in experimental human Plasmodium falciparum and Plasmodium vivax malaria.Malaria journal · 2021Article
- Analytical validation of a real-time hydrolysis probe PCR assay for quantifying Plasmodium falciparum parasites in experimentally infected human adults.Malaria journal · 2021Article
- Semimechanistic Pharmacokinetic and Pharmacodynamic Modeling of Piperaquine in a Volunteer Infection Study with Plasmodium falciparum Blood-Stage Malaria.Antimicrobial agents and chemotherapy · 2021Article
- Development and evaluation of a new Plasmodium falciparum 3D7 blood stage malaria cell bank for use in malaria volunteer infection studies.Malaria journal · 2021Article
- Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparum.Antimicrobial agents and chemotherapy · 2021Article
- Liver Function Test Abnormalities in Experimental and ClinicalThe American journal of tropical medicine and hygiene · 2020Article
- Ensemble modeling highlights importance of understanding parasite-host behavior in preclinical antimalarial drug development.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ongoing development of new antimalarial drugs and the increasing use of controlled human malaria infection (CHMI) studies to investigate their activity in early-stage clinical trials require the development of methods to analyze their pharmacodynamic effect. This is especially so for studies where quantitative PCR (qPCR) is becoming the preferred method for assessing parasite clearance as the study endpoint. We report the development and validation of an analytic approach for qPCR-determined parasite clearance data. First, in a clinical trial with the licensed antimalarial combination sulfadoxine-pyrimethamine (S/P), qPCR data were collected from 12 subjects and used to determine qPCR replicate variability and to identify outliers. Then, an iterative analytic approach based on modeling the log-linear decay of parasitemia following drug treatment was developed to determine the parasite reduction ratio (PRR) and parasite clearance half-life, both measures of parasite clearance. This analytic approach was then validated with data from 8 subjects enrolled in a second study with the licensed antimalarial drug mefloquine. By this method, the PRR and parasite clearance half-lives for S/P and Mefloquine were determined to be 38,878 (95% confidence interval [95% CI], 17,396 to 86,889) at 3.15 (95% CI, 2.93 to 3.41) days and 157 (95% CI, 130 to 189) at 6.58 (95% CI, 6.35 to 6.83) days for the respective studies. No serious adverse events occurred in the two trials, and pharmacokinetic values were within expected ranges for sulfadoxine and pyrimethamine. The robust statistical method that we have developed to analyze qPCR-derived pharmacodynamic data from CHMI studies will facilitate the assessment of the activity of a range of experimental antimalarial drugs now entering clinical trials. (This trial was registered with the Australian New Zealand Clinical Trials Registry under registration numbers ACTRN12611001203943 and ACTRN12612000323820.).
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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.