Trial reportBritish journal of clinical pharmacology2017
Epithelial desquamation observed in a phase I study of an oral cathepsin C inhibitor (GSK2793660).
Trial report in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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
27 citing papers in PubMed, 53 citations in OpenAlex.
- Safety, tolerability, pharmacokinetics and pharmacodynamics of HSK31858, a novel oral dipeptidyl peptidase-1 inhibitor, in healthy volunteers: An integrated phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study.British journal of clinical pharmacology · 2025Trial
- A randomized phase I study of the safety and pharmacokinetics of BI 1291583 in healthy Japanese male subjects.British journal of clinical pharmacology · 2025Trial
- Novel cathepsin C inhibitor, BI 1291583, intended for treatment of bronchiectasis: Phase I characterization in healthy volunteers.Clinical and translational science · 2024Trial
- Dipeptidyl Peptidase 1 Inhibitor AZD7986 Induces a Sustained, Exposure-Dependent Reduction in Neutrophil Elastase Activity in Healthy Subjects.Clinical pharmacology and therapeutics · 2018Trial
- Epithelial desquamation observed in a phase I study of an oral cathepsin C inhibitor (GSK2793660).British journal of clinical pharmacology · 2017Trial
- Tackling Neutrophilic Inflammation in Bronchiectasis: From Macrolides to Cathepsin C Inhibitors.Journal of inflammation research · 2026Review
- Identification of Marrubiin as a Cathepsin C Inhibitor for Treating Rheumatoid Arthritis.Molecules (Basel, Switzerland) · 2025Article
- Dipeptidyl peptidase 1 inhibitors and neutrophilic inflammation in bronchiectasis: a narrative review.Journal of thoracic disease · 2025Review
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Dipeptidyl peptidase-1 inhibitors in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Dipeptidyl peptidase 1 inhibitors for inflammatory respiratory diseases: mechanisms, clinical trials, and therapeutic prospects.Frontiers in pharmacology · 2025Review
- Cathepsin C in health and disease: from structural insights to therapeutic prospects.Journal of translational medicine · 2024Review
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- The preclinical and phase 1 development of the novel oral cathepsin C inhibitor BI 1291583.ERJ open research · 2024Article
- Cathepsin C regulates tumor progression via the Yes-associated protein signaling pathway in non-small cell lung cancer.American journal of cancer research · 2024Article
- BI 1291583: a novel selective inhibitor of cathepsin C with superior in vivo profile for the treatment of bronchiectasis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- A Phase 2 randomised study to establish efficacy, safety and dosing of a novel oral cathepsin C inhibitor, BI 1291583, in adults with bronchiectasis: Airleaf.ERJ open research · 2023Article
- The pharmacokinetic profile of brensocatib and its effect on pharmacodynamic biomarkers including NE, PR3, and CatG in various rodent species.Frontiers in pharmacology · 2023Article
- Novel Anti-Inflammatory Approaches to COPD.International journal of chronic obstructive pulmonary disease · 2023Review
- Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy.European respiratory review : an official journal of the European Respiratory Society · 2022Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsCathepsin C (CTSC) is necessary for the activation of several serine proteases including neutrophil elastase (NE), cathepsin G and proteinase 3. GSK2793660 is an oral, irreversible inhibitor of CTSC that is hypothesized to provide an alternative route to achieve NE inhibition and was tested in a Phase I study.
methodsSingle escalating oral doses of GSK2793660 from 0.5 to 20 mg or placebo were administered in a randomized crossover design to healthy male subjects; a separate cohort received once daily doses of 12 mg or placebo for 21 days. Data were collected on safety, pharmacokinetics, CTSC enzyme inhibition and blood biomarkers.
resultsSingle, oral doses of GSK2793660 were able to dose-dependently inhibit whole blood CTSC activity. Once daily dosing of 12 mg GSK2793660 for 21 days achieved ≥90% inhibition (95% CI: 56, 130) of CTSC within 3 h on day 1. Only modest reductions of whole blood enzyme activity of approximately 20% were observed for NE, cathepsin G and proteinase 3. Seven of 10 subjects receiving repeat doses of GSK2793660 manifested epidermal desquamation on palmar and plantar surfaces beginning 7-10 days after dosing commencement. There were no other clinically important safety findings.
conclusionsGSK2793660 inhibited CTSC activity but not the activity of downstream neutrophil serine proteases. The palmar-plantar epidermal desquamation suggests a previously unidentified role for CTSC or one of its target proteins in the maintenance and integrity of the epidermis at these sites, with some similarities to the phenotype of CTSC-deficient humans.
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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.