Trial Outcomes & Findings for Clinical Trial to Assess Pharmacodynamic Effects on Segmental Endotoxin Induced Inflammatory Response of BI 1026706 Versus Placebo (NCT NCT02657408)

Last Updated: 2019-07-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

57 participants

Primary outcome timeframe

Day 29

Results posted on

2019-07-10

Participant Flow

This was a randomised, placebo-controlled, double-blind, parallel-group study in a single trial center. In this study 57 healthy smoking subjects were entered and randomized. Subjects were allowed to rescreened twice based on investigator´s judgment with new informed consent \& unique study subject number.

All subjects (Subjs) were screened for eligibility to participate in trial. Subjs attended specialist site to ensure that they (the Subjs) met all implemented inclusion/exclusion criteria. Subjs were not to be randomised to trial drug if any of specific entry criteria was violated.

Participant milestones

Participant milestones
Measure	Placebo Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Overall Study STARTED	28	29
Overall Study COMPLETED	25	22
Overall Study NOT COMPLETED	3	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Overall Study Adverse Event	3	7

Baseline Characteristics

Treated Set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=28 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=29 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	Total n=57 Participants Total of all reporting groups
Age, Continuous	32.4 Years STANDARD_DEVIATION 8.4 • n=28 Participants • Treated Set	30.8 Years STANDARD_DEVIATION 5.4 • n=29 Participants • Treated Set	31.6 Years STANDARD_DEVIATION 7.0 • n=57 Participants • Treated Set
Sex: Female, Male Female	0 Participants n=28 Participants • Treated set	0 Participants n=29 Participants • Treated set	0 Participants n=57 Participants • Treated set
Sex: Female, Male Male	28 Participants n=28 Participants • Treated set	29 Participants n=29 Participants • Treated set	57 Participants n=57 Participants • Treated set
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=28 Participants • Treated set	0 Participants n=29 Participants • Treated set	0 Participants n=57 Participants • Treated set
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=28 Participants • Treated set	29 Participants n=29 Participants • Treated set	57 Participants n=57 Participants • Treated set
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=28 Participants • Treated set	0 Participants n=29 Participants • Treated set	0 Participants n=57 Participants • Treated set
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=28 Participants • Treated set	0 Participants n=29 Participants • Treated set	0 Participants n=57 Participants • Treated set
Race (NIH/OMB) Asian	0 Participants n=28 Participants • Treated set	0 Participants n=29 Participants • Treated set	0 Participants n=57 Participants • Treated set
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=28 Participants • Treated set	0 Participants n=29 Participants • Treated set	0 Participants n=57 Participants • Treated set
Race (NIH/OMB) Black or African American	0 Participants n=28 Participants • Treated set	0 Participants n=29 Participants • Treated set	0 Participants n=57 Participants • Treated set
Race (NIH/OMB) White	28 Participants n=28 Participants • Treated set	29 Participants n=29 Participants • Treated set	57 Participants n=57 Participants • Treated set
Race (NIH/OMB) More than one race	0 Participants n=28 Participants • Treated set	0 Participants n=29 Participants • Treated set	0 Participants n=57 Participants • Treated set
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=28 Participants • Treated set	0 Participants n=29 Participants • Treated set	0 Participants n=57 Participants • Treated set
Total neutrophil count	2.79 cells*10^3/mL STANDARD_DEVIATION 2.46 • n=24 Participants • Pharmacodynamic set (PDS): The pharmacodynamic set included all treated subjects who had evaluable cell counts for the primary or secondary endpoints 24 h after segmental LPS challenge.	3.39 cells*10^3/mL STANDARD_DEVIATION 4.13 • n=22 Participants • Pharmacodynamic set (PDS): The pharmacodynamic set included all treated subjects who had evaluable cell counts for the primary or secondary endpoints 24 h after segmental LPS challenge.	3.07 cells*10^3/mL STANDARD_DEVIATION 3.34 • n=46 Participants • Pharmacodynamic set (PDS): The pharmacodynamic set included all treated subjects who had evaluable cell counts for the primary or secondary endpoints 24 h after segmental LPS challenge.

PRIMARY outcome

Timeframe: Day 29

Population: Pharmacodynamic set (PDS): The pharmacodynamic set included all treated subjects who had evaluable cell counts for the primary or secondary endpoints 24 h after segmental LPS challenge.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=22 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Total Cell Count of Neutrophils in Bronchoalveolar Lavage (BAL) Fluid After 24 Hours of the Segmental Lipopolysaccharide (LPS) Challenge	687.02 cells*10^3/mililiter (mL) Standard Error 109.315	872.61 cells*10^3/mililiter (mL) Standard Error 145.019

SECONDARY outcome

Timeframe: Day 29

Population: PDS

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

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=22 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Differential Cell Count of Neutrophils in BAL Fluid 24 h After Segmental LPS Challenge.	54.83 Percentage of neutrophils Standard Error 3.094	55.41 Percentage of neutrophils Standard Error 3.266

SECONDARY outcome

Timeframe: Day 29

Population: PDS

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

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=22 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Total Cell Count of Eosinophil in BAL Fluid After 24 Hours of the Segmental LPS Challenge	6.95 cells*10^3/mL Standard Error 2.744	10.72 cells*10^3/mL Standard Error 4.420

SECONDARY outcome

Timeframe: Day 29

Population: PDS

Differential cell count of eosinophil in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=22 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Differential Cell Count of Eosinophil in BAL Fluid 24 h After Segmental LPS Challenge.	0.55 Percentage of eosinophil Standard Error 0.200	0.65 Percentage of eosinophil Standard Error 0.246

SECONDARY outcome

Timeframe: Day 29

Population: PDS

Total cell count of monocyte in BAL fluid after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Monocyte cell count is the only cell count which was assessed by means of flow cytometry.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=22 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Total Cell Count of Monocyte in BAL Fluid After 24 Hours of the Segmental LPS Challenge	240.04 cells*10^3/mL Standard Error 34.306	310.79 cells*10^3/mL Standard Error 46.393

SECONDARY outcome

Timeframe: Day 29

Population: PDS

Differential cell count of monocyte (determined by flow cytometry) in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Monocyte cell count is the only cell count which was assessed by means of flow cytometry.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=22 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Differential Cell Count of Monocyte in BAL Fluid 24 h After Segmental LPS Challenge.	19.16 Percentage of monocyte Standard Error 1.058	19.73 Percentage of monocyte Standard Error 1.138

SECONDARY outcome

Timeframe: Day 29

Population: PDS

Total cell count of macrophage+monocyte BAL fluid after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Cytospin microscopy method cannot clearly differentiate between macrophages and monocytes, the total and differential cell count of macrophages and monocytes are presented together.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=22 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Total Cell Count of Macrophage+Monocyte in BAL Fluid After 24 Hours of the Segmental LPS Challenge	488.95 cells*10^3/mL Standard Error 52.417	575.43 cells*10^3/mL Standard Error 64.431

SECONDARY outcome

Timeframe: Day 29

Population: PDS

Differential cell count of macrophage+monocyte in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Cytospin microscopy method cannot clearly differentiate between macrophages and monocytes, the total and differential cell count of macrophages and monocytes are presented together.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=22 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Differential Cell Count of Macrophage+Monocyte in BAL Fluid 24 h After Segmental LPS Challenge.	39.03 Percentage of macrophage+monocyte Standard Error 2.499	36.54 Percentage of macrophage+monocyte Standard Error 2.444

SECONDARY outcome

Timeframe: Day 29

Population: PDS

Total cell count of lymphocyte after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=22 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Total Cell Count of Lymphocyte in BAL After 24 Hours of the Segmental LPS Challenge	20.99 cells*10^3/mL Standard Error 3.976	16.91 cells*10^3/mL Standard Error 3.346

SECONDARY outcome

Timeframe: Day 29

Population: PDS

Differential cell count of lymphocyte in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=22 Participants Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Differential Cell Count of Lymphocyte in BAL Fluid 24 h After Segmental LPS Challenge.	1.67 Percentage of lymphocyte Standard Error 0.283	1.07 Percentage of lymphocyte Standard Error 0.190

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

BI 1026706

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=28 participants at risk Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=29 participants at risk Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Injury, poisoning and procedural complications Post procedural complication	3.6% 1/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	0.00% 0/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Nervous system disorders Presyncope	3.6% 1/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	0.00% 0/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Renal and urinary disorders Calculus urinary	0.00% 0/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	3.4% 1/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.

Other adverse events

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=28 participants at risk Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.	BI 1026706 n=29 participants at risk Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
Gastrointestinal disorders Abdominal pain upper	7.1% 2/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	3.4% 1/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Gastrointestinal disorders Diarrhoea	0.00% 0/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	6.9% 2/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Gastrointestinal disorders Flatulence	3.6% 1/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	6.9% 2/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
General disorders Pyrexia	0.00% 0/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	10.3% 3/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Infections and infestations Lower respiratory tract infection	10.7% 3/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	6.9% 2/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Infections and infestations Respiratory tract infection	0.00% 0/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	6.9% 2/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Infections and infestations Rhinitis	0.00% 0/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	6.9% 2/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Injury, poisoning and procedural complications Post procedural complication	17.9% 5/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	20.7% 6/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Injury, poisoning and procedural complications Procedural complication	10.7% 3/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	10.3% 3/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Injury, poisoning and procedural complications Procedural headache	7.1% 2/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	0.00% 0/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Injury, poisoning and procedural complications Procedural pain	10.7% 3/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	3.4% 1/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Metabolism and nutrition disorders Dehydration	7.1% 2/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	0.00% 0/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Nervous system disorders Headache	46.4% 13/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	13.8% 4/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Psychiatric disorders Agitation	7.1% 2/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	6.9% 2/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 2/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	6.9% 2/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	6.9% 2/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	10.7% 3/28 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.	17.2% 5/29 • From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.