Clinical Trial to Assess Pharmacodynamic Effects on Segmental Endotoxin Induced Inflammatory Response of BI 1026706 Versus Placebo

NCT02657408 | Completed Phase 1 Results

• 2 other identifiers: 1320.172015-001789-25
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The primary and secondary objectives of the current study are the assessments of anti-inflammatory pharmacodynamic effects on segmental endotoxin induced inflammatory response after 4 weeks treatment with BI 1026706.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Total Cell Count of Neutrophils in Bronchoalveolar Lavage (BAL) Fluid After 24 Hours of the Segmental Lipopolysaccharide (LPS) Challenge

  Total cell count of neutrophils in Bronchoalveolar Lavage (BAL) fluid after 24 hours of the segmental Lipopolysaccharide (LPS) challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the Least Square (LS) means obtained by fitting an Analysis of variance (ANOVA) model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method.

  Day 29

Secondary Outcomes (9)

• Differential Cell Count of Neutrophils in BAL Fluid 24 h After Segmental LPS Challenge.

  Day 29

• Total Cell Count of Eosinophil in BAL Fluid After 24 Hours of the Segmental LPS Challenge

  Day 29

• Differential Cell Count of Eosinophil in BAL Fluid 24 h After Segmental LPS Challenge.

  Day 29

• Total Cell Count of Monocyte in BAL Fluid After 24 Hours of the Segmental LPS Challenge

  Day 29

• Differential Cell Count of Monocyte in BAL Fluid 24 h After Segmental LPS Challenge.

  Day 29

Study Arms (2)

BI 1026706

EXPERIMENTAL

Drug: BI 1026706

Placebo

EXPERIMENTAL

Drug: Placebo

Interventions

BI 1026706 DRUG

BI 1026706

Placebo DRUG

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent consistent with ICH-Good Clinical Practice (GCP) guidelines and local legislation prior to participation in the trial.
• Healthy volunteers of both sex between 18 and 65 years (inclusive) of age, on the day of subject's signature of informed consent.
• Healthy subjects as assessed by the investigator, based on a screening examination including medical history, physical examination, vital signs (blood pressure, pulse rate, body temperature), 12-lead ECG, lung function and clinical laboratory results.
• Forced expiratory volume (FEV1) of \>80% and FEV1/Forced vital capacity(fFVC) of \>70% of the predicted normal value at screening
• Current smokers with a smoking history of at least 1 pack year and with at least 1 cigarette per day in the previous year
• BMI (Body mass index) range: \>18.5 and \< 29.9kg/m2.
• Negative urine drug screening.
• Negative breath alcohol test.
• Negative skin prick test (performed within the 12 months prior to study start or at study start)
• Females NOT of childbearing potential are defined as: Women who are postmenopausal (12 months with no menses without an alternative medical cause; in questionable cases a blood sample with simultaneous levels of FSH above 40 U/L and estradiol below 30 ng/L is confirmatory) or who are permanently sterilized (defined as hysterectomy, bilateral oophorectomy or bilateral salpingectomy).

You may not qualify if:

• History of any relevant lung disease (i.e. Chronic Obstructive Pulmonary Disease (COPD), asthma, chronic bronchitis, pulmonary fibrosis, pulmonary alveolar proteinosis (PAP), pneumocystis infection, active tuberculosis, silicosis or any other lung surfactant overproduction syndromes).
• Subjects with clinically relevant abnormal hematology, blood chemistry, or urinalysis at the screening visit
• Any finding of the medical examination (including blood pressure, pulse rate, body temperature and ECG) deviating from normal and of clinical relevance.
• Subjects with a history of any clinically significant cardiovascular, metabolic, renal (including renal stones), hepatic, gastrointestinal, hematological, dermatological, venereal, neurological, psychiatric or other major disorders.
• Subjects with a malignancy for which the subject has undergone resection, radiation therapy or chemotherapy within the last five years. Subjects with treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed to participate.
• Subjects with previous surgery of the gastro-intestinal tract likely to affect drug absorption.
• History of relevant orthostatic hypotension, fainting spells or blackouts.
• Subjects with clinically relevant infection or known ongoing clinically relevant inflammatory process.
• History of relevant allergy/hypersensitivity including allergy to drug or its excipients or medications in line with bronchoscopy (bronchodilators, sedatives and local anesthetics).
• Subjects with a marked baseline prolongation of QT/QTcB interval (such as repeated demonstration of a QTcB interval \>450 ms), or any other relevant ECG finding at screening visit (Visit 1) according to the investigator.
• Neutrophil blood count indicative of immunosuppression according to the investigator at screening visit (Visit 1).
• Subjects with previous surgeries that may have left ferromagnetic material in the body, ferromagnetic implants or pacemakers.
• Participation in another study with any investigational product within 2 months prior to screening or if screening occurs within 6 half-lives of intake of another investigational drug (whichever is greater).
• Male subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until 3 months after the trial medication treatment has finished.
• Subjects who are committed to an institution by way of official or juridical order will not be enrolled in the trial.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Fraunhofer ITEM

Hanover, 30625, Germany

Location

Related Publications (1)

• Gress C, Vogel-Claussen J, Badorrek P, Muller M, Hohl K, Konietzke M, Litzenburger T, Seibold W, Gupta A, Hohlfeld JM. The effect of bradykinin 1 receptor antagonist BI 1026706 on pulmonary inflammation after segmental lipopolysaccharide challenge in healthy smokers. Pulm Pharmacol Ther. 2023 Oct;82:102246. doi: 10.1016/j.pupt.2023.102246. Epub 2023 Aug 9.

  PMID: 37562641 DERIVED

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: January 15, 2016
• Study Start: March 11, 2016
• Primary Completion: February 14, 2017
• Study Completion: March 13, 2017
• Last Updated: July 10, 2019
• Results First Posted: July 10, 2019

Record last verified: 2019-04

Locations

DE (1)