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KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers

Overview of attention for article published in Orphanet Journal of Rare Diseases, October 2017
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  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#4 of 2,640)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (91st percentile)

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59 news outlets
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1 X user
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1 Facebook page

Citations

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29 Dimensions

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62 Mendeley
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Title
KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers
Published in
Orphanet Journal of Rare Diseases, October 2017
DOI 10.1186/s13023-017-0715-0
Pubmed ID
Authors

Saskia Koene, Edwin Spaans, Luc Van Bortel, Griet Van Lancker, Brant Delafontaine, Fabio Badilini, Julien Beyrath, Jan Smeitink

Abstract

Mitochondrial disorders are a clinically, biochemically and genetically heterogeneous group of multi-system diseases, with an unmet medical need for treatment. KH176 is an orally bio-available small molecule under development for the treatment of mitochondrial(-related) diseases. The compound is a member of a new class of drugs, acting as a potent intracellular redox-modulating agent essential for the control of oxidative and redox pathologies. The aim of this randomized, placebo controlled, double-blinded phase 1 study was to test safety, tolerability and pharmacokinetics of single and multiple doses of KH176 in healthy male volunteers. Putative effects on redox related biomarkers were explored. KH176 was well tolerated up to and including a single dose of 800 mg and multiple doses of 400 mg b.i.d. for 7 Days. However, when the QT interval was corrected for heart rate, administration of single doses of 800 and 2000 mg and at a multiple dose of 400 mg KH176 had marked effects. Post-hoc analysis of the ECGs showed clear changes in cardiac electrophysiology at single doses of 800 and 2000 mg and multiple doses of 400 mg b.i.d.. At lower doses, detailed ECG analysis showed no changes in electrophysiology compared to placebo. Exposure-response modelling of the cardiac intervals revealed an exposure range of KH176 without effects on cardiac conduction and provided a threshold of 1000 ng/mL above which changes in intervals could occur. After single- and multiple-dose administration, the pharmacokinetics of KH176 was more than dose proportional. KH176 accumulated to a small extent and food only slightly affected the pharmacokinetics of KH176, which was considered clinically irrelevant. Renal excretion of unchanged KH176 and its metabolite represents a minor pathway in the elimination of KH176. As expected in healthy volunteers no effects on redox biomarkers were observed. The study deemed that KH176 is well tolerated up to single doses of 800 mg and multiple doses of 400 mg b.i.d. and has a pharmacokinetic profile supportive for a twice daily dosing. Only at high doses, KH176 causes clinically relevant changes in cardiac electrophysiology, including prolonged QTc interval and changes in T wave morphology. A Phase 2 clinical trial (100 mg b.i.d., orally) has been conducted recently of which the final results are expected Q1 2018. NCT02544217 . Registered. ISRCTN43372293 . Retrospectively registered.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 62 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 10 16%
Student > Ph. D. Student 10 16%
Student > Master 8 13%
Researcher 8 13%
Other 3 5%
Other 3 5%
Unknown 20 32%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 18%
Medicine and Dentistry 10 16%
Pharmacology, Toxicology and Pharmaceutical Science 7 11%
Neuroscience 4 6%
Nursing and Health Professions 3 5%
Other 7 11%
Unknown 20 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 464. 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 01 January 2019.
All research outputs
#48,240
of 23,007,053 outputs
Outputs from Orphanet Journal of Rare Diseases
#4
of 2,640 outputs
Outputs of similar age
#1,133
of 325,927 outputs
Outputs of similar age from Orphanet Journal of Rare Diseases
#2
of 24 outputs
Altmetric has tracked 23,007,053 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,640 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one has done particularly well, scoring higher than 99% 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 325,927 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 99% of its contemporaries.
We're also able to compare this research output to 24 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.