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

Healthy Clinical Trial

Official title:

Pharmacokinetics, Safety and Tolerability of Different Oral Doses of Afatinib, in Subjects With Mild to Moderate Hepatic Impairment Compared to Healthy Subjects - a Phase I, Single-dose, Open-label, Dose-escalation Study in a Matched Group Design

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01298063
• Other study ID #: 1200.86
• Secondary ID: 2010-021140-18
• Status: Completed
• Phase: Phase 1
• First received: February 15, 2011
• Last updated: December 5, 2013
• Start date: February 2011

Study information

• Verified date: August 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

Healthy subjects:

1. 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).

2. Age =18 and =75 years

3. Body Mass Index =18.5 and =34 kg/m2

4. Creatinine clearance >70 mL/min according to Cockroft & Gault (for healthy volunteers, cf. Section 10.2)

5. 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:

6. 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.

7. Age =18 and =75 years

8. Body Mass Index =18.5 and =34 kg/m2

9. Creatinine clearance >40 mL/min according to Cockroft & Gault (for liver impaired subjects, cf. Section 10.2)

10. 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:

11. 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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy
• Liver Diseases

Intervention

Drug:
• Afatinib
1 tablet, once qd in the morning
• Afatinib
1 tablet, once qd in the morning
• Afatinib
1 tablet, once qd in the morning

Locations

Country	Name	City	State
Germany	1200.86.1 Boehringer Ingelheim Investigational Site	Kiel

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	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	No
Primary	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	No
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	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	No
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.	First administration of trial medication until 28 days after last administration of trial medication	No

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