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

NCT ID: NCT01298063

Last Updated: 2013-12-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28

Brief 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.

Conditions

Liver Diseases; Healthy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Afatinib Group A, B (2), D

healthy subjects, mild and moderate liver impaired subjects to receive one single dose treatment containing the highest dose afatinib

Group Type: EXPERIMENTAL

Afatinib

Intervention Type: DRUG

1 tablet, once qd in the morning

Afatinib Group B (3), D

healthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the medium dose of afatinib

Group Type: EXPERIMENTAL

Afatinib

Intervention Type: DRUG

1 tablet, once qd in the morning

Afatinib Group B (1), D

healthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the low dose of afatinib

Group Type: EXPERIMENTAL

Afatinib

Intervention Type: DRUG

1 tablet, once qd in the morning

Interventions

Afatinib

1 tablet, once qd in the morning

Intervention Type: DRUG

Afatinib

1 tablet, once qd in the morning

Intervention Type: DRUG

Afatinib

1 tablet, once qd in the morning

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

1200.86.1 Boehringer Ingelheim Investigational Site

Kiel, , Germany

Countries

Germany

Other Identifiers

2010-021140-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1200.86

Identifier Type: -

Identifier Source: org_study_id