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Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study

Overview of attention for article published in Lancet Infectious Diseases, June 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (90th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (64th percentile)

Mentioned by

news
2 news outlets
twitter
15 tweeters

Citations

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44 Dimensions

Readers on

mendeley
72 Mendeley
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Title
Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study
Published in
Lancet Infectious Diseases, June 2017
DOI 10.1016/s1473-3099(17)30171-8
Pubmed ID
Authors

James S McCarthy, Julie Lotharius, Thomas Rückle, Stephan Chalon, Margaret A Phillips, Suzanne Elliott, Silvana Sekuloski, Paul Griffin, Caroline L Ng, David A Fidock, Louise Marquart, Noelle S Williams, Nathalie Gobeau, Lidiya Bebrevska, Maria Rosario, Kennan Marsh, Jörg J Möhrle

Abstract

DSM265 is a novel antimalarial that inhibits plasmodial dihydroorotate dehydrogenase, an enzyme essential for pyrimidine biosynthesis. We investigated the safety, tolerability, and pharmacokinetics of DSM265, and tested its antimalarial activity. Healthy participants aged 18-55 years were enrolled in a two-part study: part 1, a single ascending dose (25-1200 mg), double-blind, randomised, placebo-controlled study, and part 2, an open-label, randomised, active-comparator controlled study, in which participants were inoculated with Plasmodium falciparum induced blood-stage malaria (IBSM) and treated with DSM265 (150 mg) or mefloquine (10 mg/kg). Primary endpoints were DSM265 safety, tolerability, and pharmacokinetics. Randomisation lists were created using a validated, automated system. Both parts were registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613000522718 (part 1) and number ACTRN12613000527763 (part 2). In part 1, 73 participants were enrolled between April 12, 2013, and July 14, 2015 (DSM265, n=55; placebo, n=18). In part 2, nine participants were enrolled between Sept 30 and Nov 25, 2013 (150 mg DSM265, n=7; 10 mg/kg mefloquine, n=2). In part 1, 117 adverse events were reported; no drug-related serious or severe events were reported. The most common drug-related adverse event was headache. The mean DSM265 peak plasma concentration (Cmax) ranged between 1310 ng/mL and 34 800 ng/mL and was reached in a median time (tmax) between 1·5 h and 4 h, with a mean elimination half-life between 86 h and 118 h. In part 2, the log10 parasite reduction ratio at 48 h in the DSM265 (150 mg) group was 1·55 (95% CI 1·42-1·67) and in the mefloquine (10 mg/kg) group was 2·34 (2·17-2·52), corresponding to a parasite clearance half-life of 9·4 h (8·7-10·2) and 6·2 h (5·7-6·7), respectively. The median minimum inhibitory concentration of DSM265 in blood was estimated as 1040 ng/mL (range 552-1500), resulting in a predicted single efficacious dose of 340 mg. Parasite clearance was significantly faster in participants who received mefloquine than in participants who received DSM265 (p<0·0001). The good safety profile, long elimination half-life, and antimalarial effect of DSM265 supports its development as a partner drug in a single-dose antimalarial combination treatment. Wellcome Trust, UK Department for International Development, Global Health Innovative Technology Fund, Bill & Melinda Gates Foundation.

Twitter Demographics

The data shown below were collected from the profiles of 15 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 72 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Brazil 1 1%
Unknown 71 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 18 25%
Student > Ph. D. Student 12 17%
Student > Master 11 15%
Other 6 8%
Student > Bachelor 5 7%
Other 13 18%
Unknown 7 10%
Readers by discipline Count As %
Medicine and Dentistry 15 21%
Biochemistry, Genetics and Molecular Biology 11 15%
Agricultural and Biological Sciences 11 15%
Pharmacology, Toxicology and Pharmaceutical Science 10 14%
Chemistry 7 10%
Other 10 14%
Unknown 8 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 24. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 June 2017.
All research outputs
#718,353
of 13,907,097 outputs
Outputs from Lancet Infectious Diseases
#866
of 3,796 outputs
Outputs of similar age
#24,401
of 262,554 outputs
Outputs of similar age from Lancet Infectious Diseases
#39
of 110 outputs
Altmetric has tracked 13,907,097 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,796 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 31.8. This one has done well, scoring higher than 77% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 262,554 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 90% of its contemporaries.
We're also able to compare this research output to 110 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.