Delving into the Latest Updates on BI-1291583 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

DPP-1

Mechanism

DPP-1 inhibitors(Cathepsin C inhibitors)

Therapeutic Areas

Congenital DisordersDigestive System DisordersRespiratory Diseases+ [1]

Active Indication

Cystic FibrosisNon-cystic fibrosis bronchiectasisBronchiectasis

Inactive Indication-

Originator Organization

Boehringer Ingelheim GmbH

Active Organization

Boehringer Ingelheim GmbH

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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This study is open to adults aged 18 years and older with cystic fibrosis bronchiectasis.
The purpose of this study is to find out whether a medicine called BI 1291583 is tolerated by people with cystic fibrosis bronchiectasis. Participants are put randomly into 2 groups. One group takes BI 1291583 tablets and the other group takes placebo tablets. Placebo tablets look like BI 1291583 tablets but do not contain any medicine. Participants in both groups take 1 tablet once a day for 12 weeks. Participants have twice the chance of being placed in the BI 1291583 group than in the placebo group.
Participants are in the study for about 6 months. During this time, they visit the study site 7 times. At the visits, the doctors check the health of the participants and note any health problems that could have been caused by BI 1291583.

Start Date05 Apr 2024

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT06166992 / CompletedPhase 1

Investigation of Pharmacokinetics and Absolute Oral Bioavailability of BI 1291583 Administered as an Oral Dose With an Intravenous Microtracer Dose of [14C]-BI 1291583 in Healthy Male Volunteers

The main objective of this trial is to investigate the absolute bioavailability of BI 1291583 (test treatment T, not radio-labelled) compared with BI 1291583 (C-14) (reference treatment R).

Start Date12 Dec 2023

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with BI-1291583

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100 Translational Medicine associated with BI-1291583

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100 Patents (Medical) associated with BI-1291583

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6

Literatures (Medical) associated with BI-1291583

19 Sep 2024·British journal of clinical pharmacology

A randomized phase I study of the safety and pharmacokinetics of BI 1291583 in healthy Japanese male subjects.

Article

Author: Hanada, Ryuzo ; Eleftheraki, Anastasia ; Furuichi, Takumi ; Sauter, Wiebke ; Sarubbi, Donald ; Tadayasu, Yusuke ; Nakamura, Shuhei

AIMSBronchiectasis patients face an unmet need for treatment options that reduce inflammation. Cathepsin C inhibition is expected to achieve this by reducing the activation of neutrophil-derived serine proteases. Here, we present safety and pharmacokinetic (PK) data from a Phase I trial evaluating the novel cathepsin C inhibitor BI 1291583 in healthy Japanese male subjects.METHODSThis randomized, double-blind, placebo-controlled, parallel-group study investigated BI 1291583 in healthy Japanese male subjects (jRCT2071210111) and consisted of a single-rising-dose (SRD) part and a multiple-dose (MD) part. The primary endpoint was the percentage of subjects with drug-related treatment-emergent adverse events (AEs). Secondary PK endpoints (SRD: AUC_0-∞ and C_max; MD: AUC_τ,1 and C_max,1 after first dose and AUC_τ,ss and C_max,ss after last dose), as well as further safety and PK endpoints, were also assessed.RESULTSOverall, 36 subjects (n = 24 for SRD part; n = 12 for MD part) entered this Phase I trial. BI 1291583 was safe and well tolerated across the doses tested. All AEs were of mild intensity, with no drug-related treatment-emergent AEs, deaths, serious AEs or AEs of special interest reported in either part of the trial. Following both SRD and MD administration, BI 1291583 was readily absorbed, and PK was supraproportional over the doses assessed.CONCLUSIONThe results show that BI 1291583 has an appropriate benefit-risk ratio for Japanese patients, with no safety or exposure concerns at the doses studied. Japanese patients with bronchiectasis can be safely integrated into future global clinical trials of BI 1291583, with no dose adjustment required.

01 Aug 2024·Clinical and Translational Science

Novel cathepsin C inhibitor, BI 1291583, intended for treatment of bronchiectasis: Phase I characterization in healthy volunteers

Article

Author: Kögler, Harald ; Seitz, Friedeborg ; Diefenbach, Claudia ; Hohlfeld, Jens M. ; Eleftheraki, Anastasia ; Badorrek, Philipp

AbstractNovel treatments are needed to reduce inflammation, improve symptoms, address exacerbations, and slow disease progression in bronchiectasis. Cathepsin C (CatC) inhibition promises to achieve this through reduction of neutrophil‐derived serine protease (including neutrophil elastase [NE] and proteinase 3 [PR3]) activation. Here, we present the phase I characterization of the novel CatC inhibitor, BI 1291583. Five phase I trials of BI 1291583 in healthy subjects are presented: a single‐rising‐dose study (NCT03414008) and two multiple‐rising‐dose studies (NCT03868540 and NCT04866160) assessing the safety, tolerability, pharmacodynamics, and pharmacokinetics of BI 1291583; a food effect study (NCT03837964); and a drug–drug interaction study (NCT03890887) of BI 1291583 and itraconazole. BI 1291583 was safe and well tolerated across the doses tested in these trials. Most adverse events (AEs) were mild or moderate in intensity, with no serious AEs, AEs of special interest or deaths reported in any trial. Drug‐related skin exfoliation was not reported more frequently in subjects treated with BI 1291583 compared with placebo. BI 1291583 was readily absorbed, and pharmacokinetics were supra‐proportional over the dose ranges assessed. Additionally, BI 1291583 inhibited CatC in a dose‐dependent manner, inhibited downstream NE activity, and decreased PR3 levels. No food effect was observed. Co‐administration of multiple doses of itraconazole increased BI 1291583 exposure approximately twofold. Due to these promising phase I results, a multinational phase II program of BI 1291583 in adults with bronchiectasis is ongoing (Airleaf™ [NCT05238675], Clairafly™ [NCT05865886], and Clairleaf™ [NCT05846230]).

01 Mar 2024·ERJ Open Research

The preclinical and phase 1 development of the novel oral cathepsin C inhibitor BI 1291583

Article

Author: Badorrek, Philipp ; Kögler, Harald ; Diefenbach, Claudia ; Hohlfeld, Jens M ; Kreideweiss, Stefan ; Sauter, Wiebke ; Chalmers, James D

Preclinical and phase 1 study results indicate that BI 1291583 is a reversible, highly potent and highly selective CatC inhibitor that markedly inhibits active NSP production in a dose-dependent manner, supporting phase 2 trials in bronchiectasis patients https://bit.ly/47PZ8E5.

100 Deals associated with BI-1291583

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bronchiectasis	Phase 2	TR	Boehringer Ingelheim GmbH	21 Mar 2022
Bronchiectasis	Phase 2	GR	Boehringer Ingelheim GmbH	21 Mar 2022
Bronchiectasis	Phase 2	LV	Boehringer Ingelheim GmbH	21 Mar 2022
Bronchiectasis	Phase 2	PL	Boehringer Ingelheim GmbH	21 Mar 2022
Bronchiectasis	Phase 2	CA	Boehringer Ingelheim GmbH	21 Mar 2022
Bronchiectasis	Phase 2	BG	Boehringer Ingelheim GmbH	21 Mar 2022
Bronchiectasis	Phase 2	DK	Boehringer Ingelheim GmbH	21 Mar 2022
Bronchiectasis	Phase 2	IL	Boehringer Ingelheim GmbH	21 Mar 2022
Bronchiectasis	Phase 2	GB	Boehringer Ingelheim GmbH	21 Mar 2022
Bronchiectasis	Phase 2	JP	Boehringer Ingelheim GmbH	21 Mar 2022