Figures
- FIGURE 1
Phase I study in healthy males: subject flow. #: one patient prematurely discontinued the study after taking 48 mg BI 1015550 due to an adverse event that was not considered drug-related (ligament sprain). SRD: single rising dose; MRD: multiple rising dose.
- FIGURE 2
Geometric mean plasma concentration–time profiles of BI 1015550. Phase I study in healthy males after a) single oral administration of BI 1015550 36 mg or 48 mg under fasted conditions, and b) single and multiple oral administrations of 6 mg or 12 mg twice-daily BI 1015550 under fed conditions. c) Phase Ic study in patients with idiopathic pulmonary fibrosis after single and multiple oral administration of 18 mg twice-daily BI 1015550.
- FIGURE 3
Phase Ic study in patients with idiopathic pulmonary fibrosis: patient flow. Of 10 patients treated with BI 1015550, seven were treated up to a maximum duration of 12 weeks and three up to a maximum of 4 weeks. Of five patients treated with placebo, four were treated up to a maximum duration of 12 weeks and one up to a maximum of 4 weeks. AE: adverse event; PK: pharmacokinetic. #: four patients were screened twice; ¶: other reasons for discontinuations (n=1 each) included no longer willing to participate, administrative reason, randomisation timeline, study closed and unable to perform calprotectin retest.
Tables
- TABLE 1
Phase I study in healthy male subjects: summary of adverse events (AEs)
SRD MRD Placebo BI 1015550 Placebo BI 1015550 36 mg 48 mg Total 6 mg twice daily 12 mg twice daily Total Number of subjects 6 (100.0) 6 (100.0) 6 (100.0) 12 (100.0) 8 (100.0) 8 (100.0) 8 (100.0) 16 (100.0) Subjects with any AE 1 (16.7) 4 (66.7) 4 (66.7) 8 (66.7) 3 (37.5) 2 (25.0) 5 (62.5) 7 (43.8) Subjects with investigator-defined drug-related AEs 1 (16.7) 2 (33.3) 4 (66.7) 6 (50.0) 1 (12.5) 2 (25.0) 4 (50.0) 6 (37.5) Data are presented as n (%). SRD: single rising dose; MRD: multiple rising dose.
- TABLE 2
Phase I study in healthy male subjects: summary of pharmacokinetic parameters of BI 1015550 in the single rising dose part
Parameter (unit) BI 1015550 36 mg# BI 1015550 48 mg# gMean gCV (%) gMean gCV (%) Cmax (nmol·L−1) 710 20.7 955 15.5 AUC0−∞ (nmol·h·L−1) 5910 21.2 8700¶ 17.2 fe0–120 (%) 12.5¶ 45.2 12.1+ 13.4 CLR,0–120 (mL·min−1) 30.5+ 21.5 25.2+ 20.6 gMean: geometric mean; gCV: geometric coefficient of variation; Cmax: maximum measured concentration of analyte in plasma; AUC0–∞: area under the concentration–time curve of the analyte in plasma over the time interval from 0 extrapolated to ∞; fe0–120: fraction of administered drug excreted unchanged in urine over the time interval 0–120 h after first drug administration; CLR,0–120: renal clearance of the analyte in plasma over the time interval 0–120 h after first drug administration. #: fasted, n=6; ¶: n=5; +: n=4.
- TABLE 3
Phase I study in healthy male subjects: summary of pharmacokinetic parameters of BI 1015550 in the multiple rising dose part
Parameter (unit) BI 1015550 6 mg twice daily# BI 1015550 12 mg twice daily# gMean gCV (%) gMean gCV (%) Cmax (nmol·L−1) 103 28.2 229 29.9 AUCτ,1 (nmol·h·L−1) 564 24.8 1370 15.9 Cmax,ss (nmol·L−1) 164 21.3 348 14.1 AUCτ,ss (nmol·h·L−1) 1050 25.7 2300 15.8 RA,Cmax 1.60 35.0 1.52 23.6 RA,AUC 1.85 9.91 1.68 14.8 gMean: geometric mean; gCV: geometric coefficient of variation; Cmax: maximum measured concentration of analyte in plasma; AUCτ,1: area under the concentration–time curve for the analyte in plasma over a uniform dosing interval τ after the first dose; Cmax,ss: maximum measured concentration of analyte in plasma at steady state over a uniform dosing interval τ; AUCτ,ss: area under the concentration–time curve of the analyte in plasma at steady state over a uniform dosing interval τ; RA,Cmax: accumulation ratio of the analyte in plasma after multiple dose administration over a uniform dosing interval τ, expressed as a ratio of Cmax at steady state and after a single dose; RA,AUC: accumulation ratio of the analyte in plasma after multiple dose administration over a uniform dosing interval τ, expressed as a ratio of AUC at steady state and after a single dose. #: fed, n=8.
- TABLE 4
Phase Ic study in patients with idiopathic pulmonary fibrosis: summary of adverse events (AEs)
Placebo BI 1015550
18 mg twice dailyTotal on treatment Patients treated 5 (100.0) 10 (100.0) 15 (100.0) Any AE 5 (100.0) 10 (100.0) 15 (100.0) Severe AEs 0 (0.0) 1 (10.0) 1 (6.7) Investigator-defined drug-related AE 3 (60.0) 9 (90.0) 12 (80.0) AE leading to discontinuation of study drug 0 (0.0) 1 (10.0) 1 (6.7) Patients with AESI# 0 (0.0) 0 (0.0) 0 (0.0) Patients with other significant AEs according to ICH E3 0 (0.0) 1 (10.0) 1 (6.7) Patients with SAEs 0 (0.0) 1 (10.0) 1 (6.7) Patients requiring or prolonging hospitalisation 0 (0.0) 1 (10.0) 1 (6.7) Data are presented as n (%). AESI: adverse event of special interest; ICH: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use; SAE: serious adverse event. #: hepatic injury was defined as an AESI.
- TABLE 5
Phase Ic study in patients with idiopathic pulmonary fibrosis: pharmacokinetic parameters of BI 1015550 18 mg twice daily
Parameter (unit) gMean+ gCV (%) Day 1# Cmax (nmol·L−1) 277 23.1 AUCτ,1 (nmol·h·L−1) 1990 18.2 Day 14¶ Cmax,ss (nmol·L−1) 460 41.7 AUCτ,ss (nmol·h·L−1) 3720 49.5 n=10. gMean: geometric mean; gCV: geometric coefficient of variation; Cmax: maximum measured concentration of the analyte in plasma; AUCτ,1: area under the concentration–time curve of the analyte in plasma over a uniform dosing interval τ after administration of the first dose; Cmax,ss: maximum measured concentration of analyte in plasma at steady state over a uniform dosing interval τ; AUCτ,ss: area under the concentration–time curve of the analyte in plasma at steady state over a uniform dosing interval τ at steady state. #: after the first dose; ¶: at steady state; +: n=10.
Supplementary Material
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Supplementary material 00240-2022.SUPPLEMENT
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