A Study in Healthy Men That Tests if Taking BI 1265162 by Mouth, Intravenously, or Inhaled Influences the Amount of BI 1265162 in the Blood

Absolute Bioavailability of BI 1265162 Following Oral and Inhaled Administration in Healthy Male Volunteers (an Open-label, Randomised, Single-dose, Three-period, Three-sequence Crossover Study Followed by a Fixed Treatment)

The main objective of this trial is to investigate the absolute bioavailability of BI 1265162 following administration of oral solution and inhaled (with and without charcoal) via Respimat.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BI 1265162 (T1); Drug: BI 1265162 (T2); Drug: BI 1265162 (R); Drug: BI 1265162 (T3)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany, 88397
    • Humanpharmakologisches Zentrum Biberach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion criteria:

• Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory
• Age of 18 to 50 years (inclusive)
• Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
• Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

• Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (ECG)) deviating from normal and assessed as clinically relevant by the investigator
• Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease assessed as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
• Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• Chronic or relevant acute infections
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation)
• Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
• Inability to refrain from smoking on specified trial days
• Alcohol abuse (consumption of more than 30 g per day)
• Drug abuse or positive drug screening
• Blood donation of more than 100 mL within 30 days of planned administration of trial medication or intended blood donation during the trial
• Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
• Inability to comply with the dietary regimen of the trial site
• A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
• A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
• Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
• The subject has a diagnosis history of pulmonary hyperreactivity
• A history of chronic kidney disease
• Cannot use Respimat® appropriately

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: T1-T2-R-T3	Drug: BI 1265162 (T1); oral solution; Drug: BI 1265162 (T2); Solution for inhalation; Drug: BI 1265162 (R); concentrate for i.v. solution; Drug: BI 1265162 (T3); Solution for inhalation
EXPERIMENTAL: R-T1-T2-T3	Drug: BI 1265162 (T1); oral solution; Drug: BI 1265162 (T2); Solution for inhalation; Drug: BI 1265162 (R); concentrate for i.v. solution; Drug: BI 1265162 (T3); Solution for inhalation
EXPERIMENTAL: T2-R-T1-T3	Drug: BI 1265162 (T1); oral solution; Drug: BI 1265162 (T2); Solution for inhalation; Drug: BI 1265162 (R); concentrate for i.v. solution; Drug: BI 1265162 (T3); Solution for inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of BI 1265162 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Dose-normalized, (AUC0-∞, Norm)	Area under the concentration-time curve of BI 1265162 in plasma over the time interval from 0 extrapolated to infinity, dose-normalized to 1 µg BI 1265162, (AUC0-∞, norm). Time frame for treatment T1: Within 3 hours before and 30 and 45 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours following administration of the trial drug. Time frame for treatment T2 and T3: Within 3 hours before and 2, 5, 10, 15 and 40 minutes, 1, 2, 4, 8, 10, 12 and 24 hours following administration of the trial drug. Time frame for treatment R: Within 3 hours (h) before and 5, 30 and 59 minutes (min), 1 h 5 min, 1 h 10 min, 1 h 20 min, 1 h 40 min, 2, 2 h 30 min, 3, 3 h 30 min, 4, 5, 7, 9, 11, 13 and 24 hours following administration of the trial drug.	Up to 24 hours following administration of the trial drug, see detailed time frame in the endpoint description.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Mackie A, Rascher J, Schmid M, Endriss V, Brand T, Seibold W. First clinical trials of the inhaled epithelial sodium channel inhibitor BI 1265162 in healthy volunteers. ERJ Open Res. 2021 Feb 1;7(1):00447-2020. doi: 10.1183/23120541.00447-2020. eCollection 2021 Jan.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 23, 2019
• Primary Completion (ACTUAL): December 6, 2019
• Study Completion (ACTUAL): December 6, 2019

Study Registration Dates

• First Submitted: April 5, 2019
• First Submitted That Met QC Criteria: April 5, 2019
• First Posted (ACTUAL): April 8, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 6, 2022
• Last Update Submitted That Met QC Criteria: March 16, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 1399-0014; 2018-002689-38 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: http://trials.boehringer-ingelheim.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No