Evidence map›Paper›PMID 29484635›Full record

Trial reportClinical pharmacology and therapeutics2018

Dipeptidyl Peptidase 1 Inhibitor AZD7986 Induces a Sustained, Exposure-Dependent Reduction in Neutrophil Elastase Activity in Healthy Subjects.

Robert Palmér, Jukka Mäenpää, Alexandra Jauhiainen, Bengt Larsson, John Mo, Muir Russell, James Root, Susanne Prothon, Ligia Chialda, Pablo Forte and 3 more

Open access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical pharmacology and therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
2.5field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 93 citations in OpenAlex.

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  10. The dipeptidyl peptidase 1 inhibition landscape in bronchiectasis and its future direction.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Robert PalmérQuantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Jukka MäenpääPatient Safety, Respiratory, Inflammation, Autoimmunity, Infections and Vaccines Therapeutic Area, AstraZeneca, Gothenburg, Sweden.
Alexandra JauhiainenEarly Clinical Biometrics, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Bengt LarssonRIA Translational Medicines Unit, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
John MoTranslational Biology, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Muir RussellPrecision Medicine Laboratories, Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca, Cambridge, UK.
James RootBioscience, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Susanne ProthonQuantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Ligia ChialdaParexel Early Phase Clinical Unit, Harrow, London, UK.
Pablo ForteParexel Early Phase Clinical Unit, Harrow, London, UK.
Torbjörn EgelrudUmeå University, Umeå, Sweden.
Kristina StenvallRespiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Philip GardinerQuantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
AstraZeneca (Sweden) · SEPAREXEL International (United Kingdom) · GBAstraZeneca (United Kingdom) · GBUmeå University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), are activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation. High NSP levels can be detrimental, particularly in lung tissue, and inhibition of NSPs is therefore an interesting therapeutic opportunity in multiple lung diseases, including chronic obstructive pulmonary disease (COPD) and bronchiectasis. We conducted a randomized, placebo-controlled, first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of the DPP1 inhibitor AZD7986 in healthy subjects. Pharmacokinetic and pharmacodynamic data were analyzed using nonlinear mixed effects modeling and showed that AZD7986 inhibits whole blood NE activity in an exposure-dependent, indirect manner-consistent with in vitro and preclinical predictions. Several dose-dependent, possibly DPP1-related, nonserious skin findings were observed, but these were not considered to prevent further clinical development. Overall, the study results provided confidence to progress AZD7986 to phase II and supported selection of a clinically relevant dose.

Indexed as

Administration, OralBenzoxazolesCathepsin CCysteine Proteinase InhibitorsDose-Response Relationship, DrugDrug Administration ScheduleHealthy VolunteersHumansLeukocyte ElastaseMaleModels, BiologicalNeutrophilsNonlinear DynamicsOxazepinesSerine Proteinase InhibitorsBenzoxazolesbrensocatibCathepsin CCTSC protein, humanCysteine Proteinase InhibitorsELANE protein, humanLeukocyte ElastaseOxazepinesSerine Proteinase Inhibitors

Identifiers

PMID29484635
PMCPMC6282495
OpenAlexW2789788951

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.