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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-021140-18 | EudraCT Number | EudraCT |
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Up to 38 subjects entered with the aim of entering 8 subjects with mild liver impairment (at highest dose of afatinib), 8 subjects with moderate liver impairment (at either highest dose or two lower doses) and 8 healthy matched controls to each of this two groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Afatinib Group A, B (2), D | Experimental | healthy subjects, mild and moderate liver impaired subjects to receive one single dose treatment containing the highest dose afatinib |
|
| Afatinib Group B (3), D | Experimental | healthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the medium dose of afatinib |
|
| Afatinib Group B (1), D | Experimental | healthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the low dose of afatinib |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Afatinib | Drug | 1 tablet, once qd in the morning |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under Curve From 0 to Infinity (AUC0-infinity) | AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity | 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 |
| Maximum Concentration (Cmax) | Cmax represents the maximum measured concentration of the analyte in plasma | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under Curve From 0 to tz (AUC0-tz) | 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 | 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 |
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Inclusion criteria:
Healthy subjects:
Healthy males and females according to a complete medical history, including a physical examination, vital signs (Blood Pressure, Pulse Rate), 12-lead Electrocardiogram, and clinical laboratory tests. The healthy subjects must meet the matching criteria based on the matching approach (cf. Section 3.3).
Age =18 and =75 years
Body Mass Index =18.5 and =34 kg/m2
Creatinine clearance >70 mL/min according to Cockroft & Gault (for healthy volunteers, cf. Section 10.2)
Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation. Hepatically impaired subjects as determined by a hepatologist/ gastroenterologist:
Male and female liver impaired subjects determined by results of screening classified as Child-Pugh A; Child-Pugh score of 5-6 points or as Child-Pugh B; Child-Pugh score of 7-9 points, cf. Section 10.2. Child-Pugh criteria must be stable for at least 3 months prior to screening and during the trial.
Age =18 and =75 years
Body Mass Index =18.5 and =34 kg/m2
Creatinine clearance >40 mL/min according to Cockroft & Gault (for liver impaired subjects, cf. Section 10.2)
Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation.
For all females:
Postmenopausal female subjects (postmenopausal defined as at least 1 year of spontaneous amenorrhea [in questionable cases or spontaneous amenorrhea below 1 year a blood sample with simultaneous follicle stimulating hormone (FSH) above 40 IU/l and estradiol below 30 ng/l is confirmatory]) or adequate contraception* for female subjects of childbearing potential during the study and until 2 months after study completion, e.g. any of the following: implants, injectables, combined oral contraceptives, IUD (intrauterine device), sexual abstinence for at least 1 month prior to first study drug administration, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile have to use an additional barrier method (e.g. condom).
Exclusion criteria:
Any relevant deviation from healthy conditions (excluded conditions caused by liver impairment)
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1200.86.1 Boehringer Ingelheim Investigational Site | Kiel | Germany |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| FG001 | 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). |
| FG002 | 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). |
| FG003 | 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). |
| FG004 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 50 mg Afatinib Group A | Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 mg Afatinib (One tablet qd in the morning). |
| BG001 | 30 mg Afatinib Group B1 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under Curve From 0 to Infinity (AUC0-infinity) | AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
First administration of trial medication until 28 days after last administration of trial medication
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 50 mg Afatinib Group A | Group A: Mild hepatic impaired subjects with Child Pugh A were treated with 50 mg Afatinib (One tablet qd in the morning). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| ID | Term |
|---|---|
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000077716 | Afatinib |
| ID | Term |
|---|---|
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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| Afatinib |
| Drug |
1 tablet, once qd in the morning |
|
| Afatinib | Drug | 1 tablet, once qd in the morning |
|
| Clinical Relevant Abnormalitites for Physical Examination, Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Adverse Event, Investigator's Global Tolerability | 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. | First administration of trial medication until 28 days after last administration of trial medication |
Group B1: Moderate hepatic impaired subjects with Child Pugh B were treated with 30 mg Afatinib (One tablet qd in the morning).
| BG002 | 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). |
| BG003 | 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). |
| BG004 | 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). |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | 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). |
| OG002 | 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). |
| OG003 | 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). |
| OG004 | 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). |
|
|
|
| Primary | Maximum Concentration (Cmax) | Cmax represents the maximum measured concentration of the analyte in plasma | PK analysis set. Group B1 was not included in the primary analysis set for comparison. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
|
|
|
|
| Secondary | Area Under Curve From 0 to tz (AUC0-tz) | 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 | PK analysis set. Group B1 was not included in the primary analysis set for comparison. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
|
|
|
| Secondary | Clinical Relevant Abnormalitites for Physical Examination, Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Adverse Event, Investigator's Global Tolerability | 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. | Treated set | Posted | Number | participants | First administration of trial medication until 28 days after last administration of trial medication |
|
|
|
| 0 |
| 8 |
| 3 |
| 8 |
| EG001 | 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). | 0 | 3 | 1 | 3 |
| EG002 | 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). | 0 | 8 | 1 | 8 |
| EG003 | 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). | 0 | 8 | 1 | 8 |
| EG004 | 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). | 0 | 8 | 0 | 8 |
| Dyspepsia | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 14.1 | Systematic Assessment |
|
| Hyperlipasaemia | Metabolism and nutrition disorders | MedDRA 14.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA 14.1 | Systematic Assessment |
|
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| ANOVA | Adjusted (by treatment) geometric mean ratio | 0.5281 | P-value for ratio outside interval 80 - 125 percent | Geometric mean ratio | 126.89 | Standard Deviation | 42.8 | 2-Sided | 90 | 86.028 | 187.159 | The standard deviation is actually the intra individual geometric coefficient of variation | Yes | Non-Inferiority or Equivalence | Relative bioavailability |
| ANOVA | Adjusted (by treatment) geometric mean ratio | 0.1546 | P-value for ratio outside interval 80 - 125 percent | Geometric mean ratio | 94.49 | Standard Deviation | 32.4 | 2-Sided | 90 | 71.563 | 124.764 | The standard deviation is actually the intra individual geometric coefficient of variation | Yes | Non-Inferiority or Equivalence | Relative bioavailability |
| Hyperlipasaemia |
|