Trial Outcomes & Findings for Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 655130 in Healthy Male Volunteers (NCT NCT02852824)

NCT ID: NCT02852824

Last Updated: 2024-03-18

Results Overview

Percentage of subjects with investigator defined drug-related adverse events (AEs).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

40 participants

Primary outcome timeframe

From first drug administration until the end-of-trial examination; up to 179 days. (For both, Multiple rising dose part and single dose part)

Results posted on

2024-03-18

Participant Flow

The multiple rising dose (MRD) part of the trial was double-blind, randomised and placebo-controlled within parallel dose groups. The placebo-controlled single dose (SD) part was single-blind and partially randomised.

All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites to ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be randomized to trial treatment if any one of the specific entry criteria were not met.

Participant milestones

Participant milestones
Measure	Placebo Matching to BI 655130 Multiple Dose (MD) Participants were administered multiple dose (4 single intravenous (IV) infusions 1 week apart) of 20 milligram per kilogram (mg/kg) solution for infusion of Placebo matching to BI 655130.	3 Milligram/Kilogram (mg/kg)] BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 3 mg/kg solution for infusion of BI 655130	6 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 6 mg/kg solution for infusion of BI 655130.	10 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 10 mg/kg solution for infusion of BI 655130.	20 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 20 mg/kg solution for infusion of BI 655130.	Placebo Matching to BI 655130 Single Dose (SD) Participants were administered single dose of 20 mg/kg solution for intravenous infusion of Placebo matching to BI 655130.	20 mg/kg BI 655130 Single Dose Participants were administered single dose of 20 mg/kg solution for intravenous infusion of BI 655130.
Overall Study STARTED	8	6	6	6	6	2	6
Overall Study COMPLETED	7	6	6	6	4	2	6
Overall Study NOT COMPLETED	1	0	0	0	2	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching to BI 655130 Multiple Dose (MD) Participants were administered multiple dose (4 single intravenous (IV) infusions 1 week apart) of 20 milligram per kilogram (mg/kg) solution for infusion of Placebo matching to BI 655130.	3 Milligram/Kilogram (mg/kg)] BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 3 mg/kg solution for infusion of BI 655130	6 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 6 mg/kg solution for infusion of BI 655130.	10 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 10 mg/kg solution for infusion of BI 655130.	20 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 20 mg/kg solution for infusion of BI 655130.	Placebo Matching to BI 655130 Single Dose (SD) Participants were administered single dose of 20 mg/kg solution for intravenous infusion of Placebo matching to BI 655130.	20 mg/kg BI 655130 Single Dose Participants were administered single dose of 20 mg/kg solution for intravenous infusion of BI 655130.
Overall Study Withdrawal by Subject	1	0	0	0	0	0	0
Overall Study Adverse Event	0	0	0	0	2	0	0

Baseline Characteristics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Matching to BI 655130 Multiple Dose (MD) n=8 Participants Participants were administered multiple dose (4 single intravenous (IV) infusions 1 week apart) of 20 milligram per kilogram (mg/kg) solution for infusion of Placebo matching to BI 655130.	3 Milligram/Kilogram (mg/kg)] BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 3 mg/kg solution for infusion of BI 655130	6 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 6 mg/kg solution for infusion of BI 655130.	10 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 10 mg/kg solution for infusion of BI 655130.	20 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 20 mg/kg solution for infusion of BI 655130.	Placebo Matching to BI 655130 Single Dose (SD) n=2 Participants Participants were administered single dose of 20 mg/kg solution for intravenous infusion of Placebo matching to BI 655130.	20 mg/kg BI 655130 Single Dose n=6 Participants Participants were administered single dose of 20 mg/kg solution for intravenous infusion of BI 655130.	Total n=40 Participants Total of all reporting groups
Age, Continuous	35.9 Years STANDARD_DEVIATION 7.3 • n=5 Participants • TS	37.7 Years STANDARD_DEVIATION 8.9 • n=7 Participants • TS	35.3 Years STANDARD_DEVIATION 6.4 • n=5 Participants • TS	31.0 Years STANDARD_DEVIATION 9.1 • n=4 Participants • TS	37.2 Years STANDARD_DEVIATION 7.4 • n=21 Participants • TS	46.5 Years STANDARD_DEVIATION 4.9 • n=8 Participants • TS	37.5 Years STANDARD_DEVIATION 9.9 • n=8 Participants • TS	36.3 Years STANDARD_DEVIATION 8.1 • n=24 Participants • TS
Sex: Female, Male Female	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS	0 Participants n=21 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=24 Participants • TS
Sex: Female, Male Male	8 Participants n=5 Participants • TS	6 Participants n=7 Participants • TS	6 Participants n=5 Participants • TS	6 Participants n=4 Participants • TS	6 Participants n=21 Participants • TS	2 Participants n=8 Participants • TS	6 Participants n=8 Participants • TS	40 Participants n=24 Participants • TS
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS	1 Participants n=21 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=8 Participants • TS	1 Participants n=24 Participants • TS
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants • TS	6 Participants n=7 Participants • TS	6 Participants n=5 Participants • TS	6 Participants n=4 Participants • TS	5 Participants n=21 Participants • TS	2 Participants n=8 Participants • TS	6 Participants n=8 Participants • TS	39 Participants n=24 Participants • TS
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS	0 Participants n=21 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=24 Participants • TS
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS	0 Participants n=21 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=24 Participants • TS
Race (NIH/OMB) Asian	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS	0 Participants n=21 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=24 Participants • TS
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS	0 Participants n=21 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=24 Participants • TS
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS	0 Participants n=21 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=24 Participants • TS
Race (NIH/OMB) White	8 Participants n=5 Participants • TS	6 Participants n=7 Participants • TS	6 Participants n=5 Participants • TS	6 Participants n=4 Participants • TS	6 Participants n=21 Participants • TS	2 Participants n=8 Participants • TS	6 Participants n=8 Participants • TS	40 Participants n=24 Participants • TS
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS	0 Participants n=21 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=24 Participants • TS
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS	0 Participants n=21 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=8 Participants • TS	0 Participants n=24 Participants • TS

PRIMARY outcome

Timeframe: From first drug administration until the end-of-trial examination; up to 179 days. (For both, Multiple rising dose part and single dose part)

Population: Treated set (TS): This subject set included all subjects who received trial drug.

Percentage of subjects with investigator defined drug-related adverse events (AEs).

Outcome measures

Outcome measures
Measure	Placebo Matching to BI 655130 Multiple Dose (MD) n=8 Participants Participants were administered multiple dose (4 single intravenous (IV) infusions 1 week apart) of 20 milligram per kilogram (mg/kg) solution for infusion of Placebo matching to BI 655130.	3 Milligram/Kilogram (mg/kg)] BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 3 mg/kg solution for infusion of BI 655130	6 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 6 mg/kg solution for infusion of BI 655130.	10 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 10 mg/kg solution for infusion of BI 655130.	20 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 20 mg/kg solution for infusion of BI 655130.	Placebo Matching to BI 655130 Single Dose (SD) n=2 Participants Participants were administered single dose of 20 mg/kg solution for intravenous infusion of Placebo matching to BI 655130.	20 mg/kg BI 655130 Single Dose n=6 Participants Participants were administered single dose of 20 mg/kg solution for intravenous infusion of BI 655130.
Percentage of Subjects With Drug-related Adverse Events (AEs).	50.0 Percentage of participants	16.7 Percentage of participants	66.7 Percentage of participants	33.3 Percentage of participants	100.0 Percentage of participants	0.0 Percentage of participants	33.3 Percentage of participants

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at 2 hours pre-dose and 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 hours after drug administration.

Population: Pharmacokinetic parameter set (PKS):This subject set included all subjects of the TS who provided at least 1 observation for at least 1 secondary PK endpoint without important protocol violations with respect to the statistical evaluation of PK endpoints. Only subjects from SRD part were included.

AUC0-∞, Area under the concentration-time curve of the BI 655130 in plasma over the time interval from 0 extrapolated to infinity. This endpoint only applies to the single rising dose part (SD) (20 mg/kg BI 655130 single dose).

Outcome measures

Outcome measures
Measure	Placebo Matching to BI 655130 Multiple Dose (MD) n=6 Participants Participants were administered multiple dose (4 single intravenous (IV) infusions 1 week apart) of 20 milligram per kilogram (mg/kg) solution for infusion of Placebo matching to BI 655130.	3 Milligram/Kilogram (mg/kg)] BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 3 mg/kg solution for infusion of BI 655130	6 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 6 mg/kg solution for infusion of BI 655130.	10 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 10 mg/kg solution for infusion of BI 655130.	20 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 20 mg/kg solution for infusion of BI 655130.	Placebo Matching to BI 655130 Single Dose (SD) Participants were administered single dose of 20 mg/kg solution for intravenous infusion of Placebo matching to BI 655130.	20 mg/kg BI 655130 Single Dose Participants were administered single dose of 20 mg/kg solution for intravenous infusion of BI 655130.
Area Under the Concentration-time Curve of the BI 655130 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	10500 microgramday/milliliter [μgday/mL] Geometric Coefficient of Variation 19.2	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 4200 hours. Individual time points are provided in detail in description.

Cmax, maximum measured concentration of BI 655130 in plasma for single dose and multiple dose. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg SD: Samples were collected at 2 h pre-dose, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856, 3528 and 4200 h after dosing.

Outcome measures

Outcome measures
Measure	Placebo Matching to BI 655130 Multiple Dose (MD) n=6 Participants Participants were administered multiple dose (4 single intravenous (IV) infusions 1 week apart) of 20 milligram per kilogram (mg/kg) solution for infusion of Placebo matching to BI 655130.	3 Milligram/Kilogram (mg/kg)] BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 3 mg/kg solution for infusion of BI 655130	6 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 6 mg/kg solution for infusion of BI 655130.	10 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 10 mg/kg solution for infusion of BI 655130.	20 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 20 mg/kg solution for infusion of BI 655130.	Placebo Matching to BI 655130 Single Dose (SD) Participants were administered single dose of 20 mg/kg solution for intravenous infusion of Placebo matching to BI 655130.	20 mg/kg BI 655130 Single Dose Participants were administered single dose of 20 mg/kg solution for intravenous infusion of BI 655130.
Maximum Measured Concentration of the BI 655130 in Plasma (Cmax)	77.90 microgram/milliliter [μg/mL] Geometric Coefficient of Variation 19.40	130.00 microgram/milliliter [μg/mL] Geometric Coefficient of Variation 8.48	229.00 microgram/milliliter [μg/mL] Geometric Coefficient of Variation 22.90	422.00 microgram/milliliter [μg/mL] Geometric Coefficient of Variation 18.50	490.00 microgram/milliliter [μg/mL] Geometric Coefficient of Variation 29.00	—	—

SECONDARY outcome

Timeframe: Up to 4200 hours. Individual time points are provided in detail in description.

Cmax,4, maximum measured concentration of BI 655130 in plasma after the fourth dose. Steady state was not reached, therefore Cmax,ss is presented as Cmax,4. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing.

Outcome measures

Outcome measures
Measure	Placebo Matching to BI 655130 Multiple Dose (MD) n=6 Participants Participants were administered multiple dose (4 single intravenous (IV) infusions 1 week apart) of 20 milligram per kilogram (mg/kg) solution for infusion of Placebo matching to BI 655130.	3 Milligram/Kilogram (mg/kg)] BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 3 mg/kg solution for infusion of BI 655130	6 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 6 mg/kg solution for infusion of BI 655130.	10 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 10 mg/kg solution for infusion of BI 655130.	20 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 20 mg/kg solution for infusion of BI 655130.	Placebo Matching to BI 655130 Single Dose (SD) Participants were administered single dose of 20 mg/kg solution for intravenous infusion of Placebo matching to BI 655130.	20 mg/kg BI 655130 Single Dose Participants were administered single dose of 20 mg/kg solution for intravenous infusion of BI 655130.
Maximum Measured Concentration of BI 655130 in Plasma After the Fourth Dose (Cmax,4)	141.00 microgram/milliliter [μg/mL] Geometric Coefficient of Variation 4.33	253.00 microgram/milliliter [μg/mL] Geometric Coefficient of Variation 8.70	467.00 microgram/milliliter [μg/mL] Geometric Coefficient of Variation 21.40	826.00 microgram/milliliter [μg/mL] Geometric Coefficient of Variation 15.80	—	—	—

SECONDARY outcome

Timeframe: Up to 4200 hours. Individual time points are provided in detail in description.

AUCτ,1, Area under the concentration-time curve of the BI 655130 in plasma over a uniform dosing interval τ after administration of the first dose. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing.

Outcome measures

Outcome measures
Measure	Placebo Matching to BI 655130 Multiple Dose (MD) n=6 Participants Participants were administered multiple dose (4 single intravenous (IV) infusions 1 week apart) of 20 milligram per kilogram (mg/kg) solution for infusion of Placebo matching to BI 655130.	3 Milligram/Kilogram (mg/kg)] BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 3 mg/kg solution for infusion of BI 655130	6 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 6 mg/kg solution for infusion of BI 655130.	10 mg/kg BI 655130 MD n=6 Participants Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 10 mg/kg solution for infusion of BI 655130.	20 mg/kg BI 655130 MD Participants were administered multiple dose (4 single intravenous infusions 1 week apart) of 20 mg/kg solution for infusion of BI 655130.	Placebo Matching to BI 655130 Single Dose (SD) Participants were administered single dose of 20 mg/kg solution for intravenous infusion of Placebo matching to BI 655130.	20 mg/kg BI 655130 Single Dose Participants were administered single dose of 20 mg/kg solution for intravenous infusion of BI 655130.
Area Under the Concentration-time Curve of the BI 655130 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1)	298.00 microgramday/milliliter [μgday/mL] Geometric Coefficient of Variation 9.26	552.00 microgramday/milliliter [μgday/mL] Geometric Coefficient of Variation 10.40	923.00 microgramday/milliliter [μgday/mL] Geometric Coefficient of Variation 17.30	1770.00 microgramday/milliliter [μgday/mL] Geometric Coefficient of Variation 12.50	—	—	—

SECONDARY outcome

Timeframe: Up to 4200 hours. Individual time points are provided in detail in description.

AUCτ,4, area under the concentration time curve of BI 655130 in plasma after the fourth dose. Steady state was not reached, therefore AUCτ,ss is presented as AUCτ,4. BI 655130: 3/6 mg/kg MD: Samples were collected at 2 hours(h) pre-dose, 0.5, 12, 24, 96, 166, 168.5, 180, 192, 264, 334, 336.5, 348, 360, 432, 502, 504.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 10 mg/kg MD: Samples were collected at 2 h pre-dose, 1, 12, 24, 96, 166, 169, 180, 192, 264, 334, 337, 348, 360, 432, 502, 505, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing. 20 mg/kg MD: Samples were collected at 2 h pre-dose, 1.5, 12, 24, 96, 166, 169.5, 180, 192, 264, 334, 337.5, 348, 360, 432, 502, 505.5, 516, 528, 600, 672, 840, 1008, 1176, 1344, 1512, 1848, 2184, 2856, 3528 and 4200 h after dosing.