Trial Outcomes & Findings for Safety, Tolerability, PK and PD of BI 655075 and Establishment of BI 655075 Dose(s) Effective to Reverse Prolongation of Blood Coagulation Time by Dabigatran (NCT NCT01955720)
NCT ID: NCT01955720
Last Updated: 2016-02-11
Results Overview
Percentage of subjects with at least one assay value from diluted thrombin time (dTT) or ecarin clotting time (ECT) reversed within 10min after completion of infusion. Reversal was defined as return to baseline, where the threshold for reversal to baseline was determined using PK/PD correlation between unbound sum dabigatran and the clotting parameters ECT and dTT. Measured at the end of the infusion and 10 min later.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
46 participants
Primary outcome timeframe
End of last infusion and 10 minutes after completion of last infusion of BI 655075
Results posted on
2016-02-11
Participant Flow
Participant milestones
| Measure |
5 Ida / Placebo
Subjects received dabigatran (DE) 220 mg plus idarucizumab (Ida) 5g followed by dabigatran 220 mg plus placebo 5g (high dose)
|
Placebo / 5 Ida
Subjects received dabigatran (DE) 220 mg plus placebo 5g followed by dabigatran 220 mg plus Ida 5g (high dose)
|
2.5 Ida / Placebo
Subjects received dabigatran (DE) 220 mg plus Ida 2.5g followed by dabigatran 220 mg plus placebo 2.5g (medium dose)
|
Placebo / 2.5 Ida
Subjects received dabigatran (DE) 220 mg plus placebo 2.5g followed by dabigatran 220 mg plus Ida 2.5g (medium dose)
|
1 Ida / Placebo
Subjects received dabigatran (DE) 220 mg plus Ida 1g followed by dabigatran 220 mg plus placebo 1g (low dose)
|
Placebo / 1 Ida
Subjects received dabigatran (DE) 220 mg plus placebo 1g followed by dabigatran 220 mg plus Ida 1g (low dose)
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
13
|
13
|
3
|
3
|
7
|
7
|
|
Overall Study
Healthy Subjects Aged 45-64
|
3
|
3
|
3
|
3
|
0
|
0
|
|
Overall Study
Healthy Subjects Aged 65-80
|
4
|
4
|
0
|
0
|
4
|
4
|
|
Overall Study
Subjects With Mild Renal Impairment
|
3
|
3
|
0
|
0
|
3
|
3
|
|
Overall Study
Subjects With Moderate Renal Impairment
|
3
|
3
|
0
|
0
|
0
|
0
|
|
Overall Study
COMPLETED
|
13
|
13
|
3
|
3
|
7
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability, PK and PD of BI 655075 and Establishment of BI 655075 Dose(s) Effective to Reverse Prolongation of Blood Coagulation Time by Dabigatran
Baseline characteristics by cohort
| Measure |
Total Subjects Group
n=46 Participants
The total subjects group contains the following sub-groups: high dose (5 g idarucizumab), healthy, aged 45-64 yrs: high dose (5 g idarucizumab), healthy elderly, aged 65-80 yrs: high dose (5 g idarucizumab), mild renal impairment (RI), aged 45-80 yrs: high dose (2.5 g + 2.5 g idarucizumab), with moderate RI, aged 45-80 yrs: medium dose (2.5 g idarucizumab), healthy, aged 45-64 yrs: low dose (1 g idarucizumab), healthy elderly, aged 65-80 yrs: low dose (1 g idarucizumab), with mild RI, aged 45-80 yrs.
|
|---|---|
|
Age, Continuous
|
63.8 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: End of last infusion and 10 minutes after completion of last infusion of BI 655075Population: PD Set (PDS): The PDS included all subjects from the TS who had at least 1 evaluable predose and on-treatment coagulation test measurement value for at least 1 coagulation test and who did not have important protocol violation relevant to the evaluation of PD.
Percentage of subjects with at least one assay value from diluted thrombin time (dTT) or ecarin clotting time (ECT) reversed within 10min after completion of infusion. Reversal was defined as return to baseline, where the threshold for reversal to baseline was determined using PK/PD correlation between unbound sum dabigatran and the clotting parameters ECT and dTT. Measured at the end of the infusion and 10 min later.
Outcome measures
| Measure |
Placebo
n=46 Participants
idarucizumab-matching placebo
|
Idarucizumab (Ida)
n=46 Participants
Idarucizumab (Ida).
|
220 mg/5 g HS 45-64 Yrs
HS mid-age (45-64 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
220 mg/1 g HS 65-80 Yrs
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 1g.
|
220 mg/5 g HS 65-80 Yrs
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
150 mg/1 g Mild Renal Impairment (RI)
Mild RI (creatinine clearance \[CL\] 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/5 g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg /2*2.5 g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused 2 doses of each Ida 2.5g, given 1 h apart.
|
220 mg/Plc. 5g HS 65-80 Yrs
Healthy subjects (HS) elderly (65-80 yrs) with dabigatran (DE) 220 mg/plc. 5g.
|
150 mg/1g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/Plc. 1g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 1g
|
150 mg/5g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg/Plc. 5g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 5g
|
150 mg /2*2.5g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each Ida 2.5g, given 1 h apart.
|
150 mg /Plc. 2*2.5g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each plc. 2.5g, given 1 h apart.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Reversal of Dabigatran-induced Prolongation of Blood Coagulation Time
at least one time point, dTT
|
0.0 percentage of participants
|
100.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Reversal of Dabigatran-induced Prolongation of Blood Coagulation Time
both time points, dTT
|
0.0 percentage of participants
|
100.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Reversal of Dabigatran-induced Prolongation of Blood Coagulation Time
at least one time point, ECT
|
0.0 percentage of participants
|
100.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Reversal of Dabigatran-induced Prolongation of Blood Coagulation Time
both time points, ECT
|
0.0 percentage of participants
|
100.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From baseline up to the start of follow-up period (from Day 1 to Day 35)Population: Treated Set (TS): All randomised subjects who received at least 1 dose of trial medication were included in the treated set.
The percentage of subjects with possibly drug-related AEs (as defined by the investigator) during the treatment period.
Outcome measures
| Measure |
Placebo
n=46 Participants
idarucizumab-matching placebo
|
Idarucizumab (Ida)
Idarucizumab (Ida).
|
220 mg/5 g HS 45-64 Yrs
HS mid-age (45-64 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
220 mg/1 g HS 65-80 Yrs
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 1g.
|
220 mg/5 g HS 65-80 Yrs
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
150 mg/1 g Mild Renal Impairment (RI)
Mild RI (creatinine clearance \[CL\] 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/5 g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg /2*2.5 g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused 2 doses of each Ida 2.5g, given 1 h apart.
|
220 mg/Plc. 5g HS 65-80 Yrs
Healthy subjects (HS) elderly (65-80 yrs) with dabigatran (DE) 220 mg/plc. 5g.
|
150 mg/1g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/Plc. 1g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 1g
|
150 mg/5g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg/Plc. 5g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 5g
|
150 mg /2*2.5g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each Ida 2.5g, given 1 h apart.
|
150 mg /Plc. 2*2.5g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each plc. 2.5g, given 1 h apart.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
The Percentage of Subjects With Drug-related Adverse Events
|
13.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Day 4 to Day 9 (details in description)Population: Pharmacokinetic Set -Ida (PKS-Ida): included all treated subjects who have received at least 1 dose of idarucizumab and who provided data for at least 1 secondary or other PK endpoint in any treatment period, which was judged as evaluable for PK and was not affected by protocol violations relevant to the statistical evaluation of PK endpoints.
AUC0-infinity. PK/PD sampling time: (p=predose, D=day) 1. single medium or high dose, healthy subjects(HS) mid-age (45-64 yrs): D4: 8:55p, 9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00,01:00; D5: 9:00p, 21:00. D6: 9:00. 2. single low or high dose, HS elderly or mild renal impaired: D4: 8:55p, 9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00,01:00; D5: 9:00; D6: 9:00; D7: 9:00; additional sampling for renal impaired: D8: 9:00;D9: 9:00. 3. high 2 doses, moderate renal impaired: D4: 8:55p, 9:00, 9:10,9:30,9:55p, 10:00,10:10,10:30,11:00, 13:00, 15:00, 19:00, 21:00, 01:00; D5: 9:00; D6: 9:00; D7: 9:00; additional sampling for renal impaired: D8:9:00; D9:9:00.
Outcome measures
| Measure |
Placebo
n=6 Participants
idarucizumab-matching placebo
|
Idarucizumab (Ida)
n=6 Participants
Idarucizumab (Ida).
|
220 mg/5 g HS 45-64 Yrs
n=6 Participants
HS mid-age (45-64 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
220 mg/1 g HS 65-80 Yrs
n=8 Participants
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 1g.
|
220 mg/5 g HS 65-80 Yrs
n=8 Participants
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
150 mg/1 g Mild Renal Impairment (RI)
n=6 Participants
Mild RI (creatinine clearance \[CL\] 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/5 g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg /2*2.5 g Moderate RI (CL 30-60)
n=6 Participants
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused 2 doses of each Ida 2.5g, given 1 h apart.
|
220 mg/Plc. 5g HS 65-80 Yrs
Healthy subjects (HS) elderly (65-80 yrs) with dabigatran (DE) 220 mg/plc. 5g.
|
150 mg/1g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/Plc. 1g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 1g
|
150 mg/5g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg/Plc. 5g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 5g
|
150 mg /2*2.5g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each Ida 2.5g, given 1 h apart.
|
150 mg /Plc. 2*2.5g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each plc. 2.5g, given 1 h apart.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC0-infinity (Area Under the Concentration-time Curve of Idarucizumab (Ida) in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
|
22200 nmol*h/L
Geometric Coefficient of Variation 12.7
|
20600 nmol*h/L
Geometric Coefficient of Variation 10.6
|
37000 nmol*h/L
Geometric Coefficient of Variation 18.4
|
8560 nmol*h/L
Geometric Coefficient of Variation 15.2
|
43900 nmol*h/L
Geometric Coefficient of Variation 18.7
|
10700 nmol*h/L
Geometric Coefficient of Variation 14.1
|
53100 nmol*h/L
Geometric Coefficient of Variation 11.1
|
67900 nmol*h/L
Geometric Coefficient of Variation 11.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: from 2h to12h of post DE dose at steady state (details in description)Population: PKS-DE: The PKS-DE included all treated subjects who have received at least 1 dose of DE and who provided data for at least 1 secondary or further PK endpoint in any treatment period, which was judged as evaluable for PK and was not affected by (important) protocol violations relevant to the statistical evaluation of PK endpoints.
PK/PD sampling time:(d=dose,D=Day,p=predose) 1. single medium or high dose,healthy, mid-age (45-64 yrs): D4: 7:00p,8:55p,9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00, 01:00; D5:9:00p,11:00,21:00p; D6:9:00p, 21:00p; D7:9:00p, 11:00. 2. single low or high dose,healthy elder or mild renal impaired: D4:7:00p,8:55p,9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00,01:00;D5:9:00;D6:9:00;D7:9:00; additional sampling for renal impaired: D8:9:00;D9:9:00. 3. high 2 doses, moderate renal impaired: D4:7:00p,8:55p,9:00,9:10,9:30,9:55p,10:00,10:10,10:30,11:00,13:00,15:00,19:00,21:00,01:00;D5:9:00;D6:9:00; D7:9:00; additional sampling for renal impaired: D8:9:00;D9:9:00.
Outcome measures
| Measure |
Placebo
n=6 Participants
idarucizumab-matching placebo
|
Idarucizumab (Ida)
n=6 Participants
Idarucizumab (Ida).
|
220 mg/5 g HS 45-64 Yrs
n=6 Participants
HS mid-age (45-64 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
220 mg/1 g HS 65-80 Yrs
n=6 Participants
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 1g.
|
220 mg/5 g HS 65-80 Yrs
n=6 Participants
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
150 mg/1 g Mild Renal Impairment (RI)
n=8 Participants
Mild RI (creatinine clearance \[CL\] 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/5 g Mild RI (CL 60-90)
n=8 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg /2*2.5 g Moderate RI (CL 30-60)
n=8 Participants
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused 2 doses of each Ida 2.5g, given 1 h apart.
|
220 mg/Plc. 5g HS 65-80 Yrs
n=8 Participants
Healthy subjects (HS) elderly (65-80 yrs) with dabigatran (DE) 220 mg/plc. 5g.
|
150 mg/1g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/Plc. 1g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 1g
|
150 mg/5g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg/Plc. 5g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 5g
|
150 mg /2*2.5g Moderate RI (CL 30-60)
n=6 Participants
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each Ida 2.5g, given 1 h apart.
|
150 mg /Plc. 2*2.5g Moderate RI (CL 30-60)
n=6 Participants
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each plc. 2.5g, given 1 h apart.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC2-12, ss (Area Under the Concentration-time Curve of Unbound Sum Dabigatran (DE) in Plasma at Steady State Over the Time Interval From 2 to 12h)
|
18.5 ng*h/mL
Geometric Coefficient of Variation 75.7
|
924 ng*h/mL
Geometric Coefficient of Variation 25.6
|
36.0 ng*h/mL
Geometric Coefficient of Variation 125
|
10.6 ng*h/mL
Geometric Coefficient of Variation 11.3
|
933 ng*h/mL
Geometric Coefficient of Variation 39.2
|
284 ng*h/mL
Geometric Coefficient of Variation 66.3
|
1220 ng*h/mL
Geometric Coefficient of Variation 40.0
|
11.6 ng*h/mL
Geometric Coefficient of Variation 23.8
|
1270 ng*h/mL
Geometric Coefficient of Variation 32.8
|
100 ng*h/mL
Geometric Coefficient of Variation 192
|
929 ng*h/mL
Geometric Coefficient of Variation 56.0
|
10.0 ng*h/mL
Geometric Coefficient of Variation 0.0828
|
876 ng*h/mL
Geometric Coefficient of Variation 40.5
|
10.2 ng*h/mL
Geometric Coefficient of Variation 3.95
|
1440 ng*h/mL
Geometric Coefficient of Variation 32.3
|
SECONDARY outcome
Timeframe: From 0 to 74h post of last DE dose (details in description)Population: Pharmacokinetic Set - DE (PKS-DE): The PKS-DE included all treated subjects who have received at least 1 dose of DE and who provided data for at least 1 secondary or further PK endpoint in any treatment period, which was judged as evaluable for PK and was not affected by protocol violations relevant to the statistical evaluation of PK endpoints.
Urinary excretion of sum dabigatran from the time point t1 to t2 at steady state. PK Urine sampling time: Urine sampling relative to first DE administration: Planned times 72:00 - 73:55h, 73:55 - 80:00h, 80:00 - 86:00h, 86:00 - 98:00h, 98:00 - 122:00h, 122:00 - 146:00h; additional sampling for renal impaired: 146:00 - 170:00; 170:00 - 194:00h. Ae0-26,ss was not measured in Period 3 (re-exposure period). Ae0-74,ss was not measured in healthy subjects aged 45 to 64 years.
Outcome measures
| Measure |
Placebo
n=6 Participants
idarucizumab-matching placebo
|
Idarucizumab (Ida)
n=6 Participants
Idarucizumab (Ida).
|
220 mg/5 g HS 45-64 Yrs
HS mid-age (45-64 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
220 mg/1 g HS 65-80 Yrs
n=6 Participants
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 1g.
|
220 mg/5 g HS 65-80 Yrs
n=6 Participants
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
150 mg/1 g Mild Renal Impairment (RI)
n=8 Participants
Mild RI (creatinine clearance \[CL\] 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/5 g Mild RI (CL 60-90)
n=8 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg /2*2.5 g Moderate RI (CL 30-60)
n=8 Participants
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused 2 doses of each Ida 2.5g, given 1 h apart.
|
220 mg/Plc. 5g HS 65-80 Yrs
n=8 Participants
Healthy subjects (HS) elderly (65-80 yrs) with dabigatran (DE) 220 mg/plc. 5g.
|
150 mg/1g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/Plc. 1g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 1g
|
150 mg/5g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg/Plc. 5g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 5g
|
150 mg /2*2.5g Moderate RI (CL 30-60)
n=6 Participants
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each Ida 2.5g, given 1 h apart.
|
150 mg /Plc. 2*2.5g Moderate RI (CL 30-60)
n=6 Participants
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each plc. 2.5g, given 1 h apart.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Aet1-t2, ss (Amount of DE Eliminated in Urine From the Time Point t1 to Time Point t2)
Ae0-26,ss(N=6,6,0,6,6,8,8,8,8,6,6,6,6,6,6)
|
6080 μg
Geometric Coefficient of Variation 26.5
|
7460 μg
Geometric Coefficient of Variation 21.0
|
—
|
7560 μg
Geometric Coefficient of Variation 47.2
|
7790 μg
Geometric Coefficient of Variation 43.9
|
8490 μg
Geometric Coefficient of Variation 29.4
|
8870 μg
Geometric Coefficient of Variation 41.8
|
7460 μg
Geometric Coefficient of Variation 39.6
|
10600 μg
Geometric Coefficient of Variation 21.9
|
5800 μg
Geometric Coefficient of Variation 39.0
|
6040 μg
Geometric Coefficient of Variation 44.7
|
4020 μg
Geometric Coefficient of Variation 58.3
|
6280 μg
Geometric Coefficient of Variation 38.4
|
4760 μg
Geometric Coefficient of Variation 26.7
|
8880 μg
Geometric Coefficient of Variation 29.8
|
|
Aet1-t2, ss (Amount of DE Eliminated in Urine From the Time Point t1 to Time Point t2)
Ae0-74,ss(N=0,0,0,0,0,8,8,8,8,6,6,6,6,6,6)
|
NA μg
Geometric Coefficient of Variation NA
not measured in healthy subjects aged 45 to 64 years.
|
NA μg
Geometric Coefficient of Variation NA
not measured in healthy subjects aged 45 to 64 years.
|
—
|
NA μg
Geometric Coefficient of Variation NA
not measured in healthy subjects aged 45 to 64 years.
|
NA μg
Geometric Coefficient of Variation NA
not measured in healthy subjects aged 45 to 64 years.
|
10700 μg
Geometric Coefficient of Variation 22.0
|
10300 μg
Geometric Coefficient of Variation 40.8
|
13900 μg
Geometric Coefficient of Variation 26.1
|
12800 μg
Geometric Coefficient of Variation 20.6
|
7760 μg
Geometric Coefficient of Variation 38.8
|
7170 μg
Geometric Coefficient of Variation 45.8
|
9730 μg
Geometric Coefficient of Variation 35.3
|
7690 μg
Geometric Coefficient of Variation 39.1
|
11100 μg
Geometric Coefficient of Variation 24.5
|
10800 μg
Geometric Coefficient of Variation 30.4
|
SECONDARY outcome
Timeframe: From Ida administration to 4 days post dose (details in description)Population: PKS-Ida
Cmax. PK/PD sampling time: (p=predose, D=day) 1. single medium or high dose, HS mid-age (45-64 yrs): D4: 8:55p, 9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00,01:00; D5: 9:00p, 21:00. D6: 9:00. 2. single low or high dose, healthy elderly or mild RI: D4: 8:55p, 9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00,01:00; D5: 9:00; D6: 9:00; D7: 9:00; additional sampling for RI: D8: 9:00;D9: 9:00. 3. high 2 doses, moderate RI: D4: 8:55p, 9:00, 9:10,9:30,9:55p, 10:00,10:10,10:30,11:00, 13:00, 15:00, 19:00, 21:00, 01:00; D5: 9:00; D6: 9:00; D7: 9:00; additional sampling for RI: D8:9:00; D9:9:00.
Outcome measures
| Measure |
Placebo
n=6 Participants
idarucizumab-matching placebo
|
Idarucizumab (Ida)
n=6 Participants
Idarucizumab (Ida).
|
220 mg/5 g HS 45-64 Yrs
n=6 Participants
HS mid-age (45-64 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
220 mg/1 g HS 65-80 Yrs
n=8 Participants
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 1g.
|
220 mg/5 g HS 65-80 Yrs
n=8 Participants
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
150 mg/1 g Mild Renal Impairment (RI)
n=6 Participants
Mild RI (creatinine clearance \[CL\] 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/5 g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg /2*2.5 g Moderate RI (CL 30-60)
n=6 Participants
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused 2 doses of each Ida 2.5g, given 1 h apart.
|
220 mg/Plc. 5g HS 65-80 Yrs
Healthy subjects (HS) elderly (65-80 yrs) with dabigatran (DE) 220 mg/plc. 5g.
|
150 mg/1g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/Plc. 1g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 1g
|
150 mg/5g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg/Plc. 5g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 5g
|
150 mg /2*2.5g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each Ida 2.5g, given 1 h apart.
|
150 mg /Plc. 2*2.5g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each plc. 2.5g, given 1 h apart.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax (Maximum Measured Concentration of the Ida in Plasma)
|
15700 nmol/L
Geometric Coefficient of Variation 14.3
|
14900 nmol/L
Geometric Coefficient of Variation 12.0
|
25000 nmol/L
Geometric Coefficient of Variation 16.9
|
5790 nmol/L
Geometric Coefficient of Variation 16.4
|
28300 nmol/L
Geometric Coefficient of Variation 28.9
|
6940 nmol/L
Geometric Coefficient of Variation 19.4
|
32100 nmol/L
Geometric Coefficient of Variation 17.4
|
25600 nmol/L
Geometric Coefficient of Variation 11.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: from 0 to 6 hours of post Ida dose (details in description)Population: PKS-Ida: The PKS-Ida included all treated subjects who have received at least 1 dose of idarucizumab and who provided data for at least 1 secondary or other PK endpoint in any treatment period, which was judged as evaluable for PK and was not affected by (important) protocol violations relevant to the statistical evaluation of PK endpoints.
Ae0-6 (Amount of Ida Eliminated in Urine From the Time Point 0 to Time point 6 h). PK Urine sampling time: Urine sampling relative to DE administration: Planned times 72:00 - 73:55h, 73:55 - 80:00h, 80:00 - 86:00h, 86:00 - 98:00h, 98:00 - 122:00h, 122:00 - 146:00h; additional sampling for renal impaired: 146:00 - 170:00; 170:00 - 194:00h.
Outcome measures
| Measure |
Placebo
n=6 Participants
idarucizumab-matching placebo
|
Idarucizumab (Ida)
Idarucizumab (Ida).
|
220 mg/5 g HS 45-64 Yrs
n=6 Participants
HS mid-age (45-64 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
220 mg/1 g HS 65-80 Yrs
n=8 Participants
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 1g.
|
220 mg/5 g HS 65-80 Yrs
n=8 Participants
HS elderly (65-80 yrs) with dabigatran (DE) 220 mg/Ida 5g.
|
150 mg/1 g Mild Renal Impairment (RI)
n=6 Participants
Mild RI (creatinine clearance \[CL\] 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/5 g Mild RI (CL 60-90)
n=6 Participants
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg /2*2.5 g Moderate RI (CL 30-60)
n=6 Participants
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused 2 doses of each Ida 2.5g, given 1 h apart.
|
220 mg/Plc. 5g HS 65-80 Yrs
Healthy subjects (HS) elderly (65-80 yrs) with dabigatran (DE) 220 mg/plc. 5g.
|
150 mg/1g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 1g
|
150 mg/Plc. 1g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 1g
|
150 mg/5g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/Ida 5g
|
150 mg/Plc. 5g Mild RI (CL 60-90)
Mild RI (CL 60-90) with dabigatran (DE) 150 mg/plc. 5g
|
150 mg /2*2.5g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each Ida 2.5g, given 1 h apart.
|
150 mg /Plc. 2*2.5g Moderate RI (CL 30-60)
Moderate RI (CL 30-60) with dabigatran (DE) 150 mg and were infused as 2 doses of each plc. 2.5g, given 1 h apart.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Ae0-6 (Amount of Ida Eliminated in Urine From the Time Point 0 to Time Point 6 h)
|
13.5 umol
Geometric Coefficient of Variation 32.6
|
—
|
33.5 umol
Geometric Coefficient of Variation 60.0
|
1.97 umol
Geometric Coefficient of Variation 69.0
|
41.6 umol
Geometric Coefficient of Variation 13.7
|
2.60 umol
Geometric Coefficient of Variation 46.7
|
33.4 umol
Geometric Coefficient of Variation 48.9
|
31.3 umol
Geometric Coefficient of Variation 89.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Dabigatran Etexilate (DE)
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Low (1g) Idarucizumab Dose
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Medium (2.5g) Idarucizumab Dose
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
High (5g) Idarucizumab Dose
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Low (1g) Placebo Dose
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Medium (2.5g) Placebo Dose
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
High (5g) Placebo Dose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Dabigatran Etexilate (DE)
n=46 participants at risk
subjects with Dabigatran etexilate (DE) treatment
|
Low (1g) Idarucizumab Dose
n=14 participants at risk
Subjects with low 1g idarucizumab dose treatment
|
Medium (2.5g) Idarucizumab Dose
n=12 participants at risk
Subjects with medium (2.5g) idarucizumab dose treatment
|
High (5g) Idarucizumab Dose
n=26 participants at risk
Subjects with high (5g) idarucizumab dose treatment
|
Low (1g) Placebo Dose
n=14 participants at risk
Subjects with low (1g) placebo dose treatment
|
Medium (2.5g) Placebo Dose
n=12 participants at risk
Subjects with medium (2.5g) placebo dose treatment
|
High (5g) Placebo Dose
n=26 participants at risk
Subjects with high (5g) placebo dose treatment
|
|---|---|---|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
7.1%
1/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Nervous system disorders
Dizziness
|
0.00%
0/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
7.1%
1/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Nervous system disorders
Headache
|
15.2%
7/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
21.4%
3/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
8.3%
1/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Nervous system disorders
Paraesthesia
|
2.2%
1/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
7.1%
1/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.3%
2/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
3.8%
1/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
7.1%
1/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Gastrointestinal disorders
Abdominal discomfort
|
4.3%
2/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
3.8%
1/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
8.3%
1/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
8.3%
1/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Gastrointestinal disorders
Nausea
|
8.7%
4/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
8.3%
1/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
8.3%
1/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
8.3%
1/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.2%
1/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
7.1%
1/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.2%
1/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
7.1%
1/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
General disorders
Application site dermatitis
|
0.00%
0/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
8.3%
1/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
8.3%
1/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.00%
0/46 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
7.1%
1/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
7.1%
1/14 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/12 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
0.00%
0/26 • From the study drug administration up to start of follow-up period (from Day 1 to Day 35).
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim pharmaceuticals
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