Dataset Information

First clinical trials of the inhaled epithelial sodium channel inhibitor BI 1265162 in healthy volunteers.

ABSTRACT:

Background

Inhibition of the epithelial sodium channel (ENaC) represents a mutation-agnostic therapeutic approach to restore airway surface liquid hydration and mucociliary clearance in patients with cystic fibrosis. BI 1265162 is an inhaled ENaC inhibitor with demonstrated preclinical efficacy.

Methods

Three phase I trials of BI 1265162 in healthy male subjects are presented: NCT03349723 (single-rising-dose trial evaluating safety, tolerability and pharmacokinetics (PK)); NCT03576144 (multiple-rising-dose trial evaluating safety, tolerability and PK); and NCT03907280 (absolute bioavailability trial).

Results

BI 1265162 single doses ?1200?µg and multiple doses of 600?µg were well tolerated. Adverse events were balanced across treatment groups, were of mainly mild or moderate intensity and resolved by trial-end. One subject discontinued from trial medication on day 7 (asymptomatic hyperkalaemia adverse event; recovered day 8). One subject experienced a serious adverse event (neuropathia vestibularis) leading to hospitalisation and missed one of the four dosing periods. Both events were not considered to be drug-related and subjects recovered. BI 1265162 displayed dose-proportional, time-independent PK; maximum accumulation was 1.6-fold; calculated effective elimination half-life was 3.6-8.7?h over the dose ranges tested. Renal excretion was not a major drug elimination route. Oral and inhaled dosing (±activated oral charcoal) absolute bioavailability was 0.50% and ?40%, respectively.

Conclusion

BI 1265162 single or multiple doses up to 6.5?days were well tolerated. Systemic exposures mainly represent drug absorbed through the lungs and not the gastrointestinal tract, with ?40% of the inhaled dose reaching the systemic circulation. Accumulation was minimal. Twice-daily dosing is supported for future development.

SUBMITTER: Mackie A

PROVIDER: S-EPMC7861022 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

First clinical trials of the inhaled epithelial sodium channel inhibitor BI 1265162 in healthy volunteers.

Mackie Alison A Rascher Juliane J Schmid Marion M Endriss Verena V Brand Tobias T Seibold Wolfgang W

ERJ open research 20210101 1

<h4>Background</h4>Inhibition of the epithelial sodium channel (ENaC) represents a mutation-agnostic therapeutic approach to restore airway surface liquid hydration and mucociliary clearance in patients with cystic fibrosis. BI 1265162 is an inhaled ENaC inhibitor with demonstrated preclinical efficacy.<h4>Methods</h4>Three phase I trials of BI 1265162 in healthy male subjects are presented: NCT03349723 (single-rising-dose trial evaluating safety, tolerability and pharmacokinetics (PK)); NCT0357 ...[more]

PMID: 33569494

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Dataset Information

First clinical trials of the inhaled epithelial sodium channel inhibitor BI 1265162 in healthy volunteers.

Background

Methods

Results

Conclusion

Publications

First clinical trials of the inhaled epithelial sodium channel inhibitor BI 1265162 in healthy volunteers.

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