Trial Outcomes & Findings for Influence of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of Various Doses of Afatinib (NCT NCT01298063)

Results Overview

AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

35 participants

Primary outcome timeframe

30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing

Results posted on

2013-12-31

Participant Flow

Participant milestones

Participant milestones
Measure	50 mg Afatinib Group A Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 milligram (mg) Afatinib (One tablet qd in the morning).	30 mg Afatinib Group B1 Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group B2 Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group C Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group D Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).
Overall Study STARTED	8	3	8	8	8
Overall Study COMPLETED	8	3	8	8	8
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Influence of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of Various Doses of Afatinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	50 mg Afatinib Group A n=8 Participants Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 mg Afatinib (One tablet qd in the morning).	30 mg Afatinib Group B1 n=3 Participants Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group B2 n=8 Participants Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group C n=8 Participants Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group D n=8 Participants Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).	Total n=35 Participants Total of all reporting groups
Age, Continuous	53.9 years STANDARD_DEVIATION 9.0 • n=5 Participants	64.3 years STANDARD_DEVIATION 6.1 • n=7 Participants	54.8 years STANDARD_DEVIATION 9.0 • n=5 Participants	55.9 years STANDARD_DEVIATION 12.6 • n=4 Participants	53.1 years STANDARD_DEVIATION 7.9 • n=21 Participants	55.3 years STANDARD_DEVIATION 9.5 • n=8 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants	10 Participants n=8 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	25 Participants n=8 Participants

PRIMARY outcome

Timeframe: 30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing

Population: Pharmacokinetic (PK) analysis set includes all evaluable matched subjects in the treated set providing at least 1 observation for at least 1 PK endpoint without important protocol violations. Group B1 was not included in the primary analysis set for comparison.

AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity

Outcome measures

Outcome measures
Measure	50 mg Afatinib Group A n=8 Participants Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 milligram (mg) Afatinib (One tablet qd in the morning).	30 mg Afatinib Group B1 n=3 Participants Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group B2 n=8 Participants Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group C n=8 Participants Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group D n=8 Participants Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).
Area Under Curve From 0 to Infinity (AUC0-infinity)	886 ng*h/mL Geometric Coefficient of Variation 53.7	552 ng*h/mL Geometric Coefficient of Variation 42.1	934 ng*h/mL Geometric Coefficient of Variation 31.0	956 ng*h/mL Geometric Coefficient of Variation 22.7	985 ng*h/mL Geometric Coefficient of Variation 32.3

PRIMARY outcome

Timeframe: 30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing

Population: PK analysis set. Group B1 was not included in the primary analysis set for comparison.

Cmax represents the maximum measured concentration of the analyte in plasma

Outcome measures

Outcome measures
Measure	50 mg Afatinib Group A n=8 Participants Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 milligram (mg) Afatinib (One tablet qd in the morning).	30 mg Afatinib Group B1 n=3 Participants Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group B2 n=8 Participants Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group C n=8 Participants Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group D n=8 Participants Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).
Maximum Concentration (Cmax)	33.7 ng/mL Geometric Coefficient of Variation 51.7	17.5 ng/mL Geometric Coefficient of Variation 44.1	39.5 ng/mL Geometric Coefficient of Variation 40.1	30.7 ng/mL Geometric Coefficient of Variation 33.7	31.1 ng/mL Geometric Coefficient of Variation 46.0

SECONDARY outcome

Timeframe: 30 minutes (min) prior to first dosing and 30 min, 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 240 h after first dosing

Population: PK analysis set. Group B1 was not included in the primary analysis set for comparison.

AUC0-tz represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point

Outcome measures

Outcome measures
Measure	50 mg Afatinib Group A n=8 Participants Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 milligram (mg) Afatinib (One tablet qd in the morning).	30 mg Afatinib Group B1 n=3 Participants Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group B2 n=8 Participants Group B2: Moderate hepatic impaired subjects with Child Pugh B were treated with 50 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group C n=8 Participants Group C: Subjects with normal hepatic function matching to subjects in group A were treated with 50 mg Afatinib (One tablet qd in the morning).	50 mg Afatinib Group D n=8 Participants Group D: Subjects with normal hepatic function matching to subjects in group B2 were treated with 50 mg Afatinib (One tablet qd in the morning).
Area Under Curve From 0 to tz (AUC0-tz)	842 ng*h/mL Geometric Coefficient of Variation 50.8	519 ng*h/mL Geometric Coefficient of Variation 39.1	904 ng*h/mL Geometric Coefficient of Variation 31.4	930 ng*h/mL Geometric Coefficient of Variation 22.5	956 ng*h/mL Geometric Coefficient of Variation 33.3

SECONDARY outcome

Timeframe: First administration of trial medication until 28 days after last administration of trial medication

Population: Treated set

Clinical relevant abnormalitites for physical examination, vital signs, 12-lead electrocardiogramm (ECG), clinical laboratory test (including hematology, clinical chemistry, coagulation, urinalysis), adverse event, investigator's global tolerability. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.