Influence of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of Various Doses of Afatinib
Condition: Liver Diseases; Healthy
MeSH terms: Liver Diseases
Intervention: Afatinib; Afatinib; Afatinib
Intervention description: 1 tablet, once qd in the morning; 1 tablet, once qd in the morning; 1 tablet, once qd in the morning
Intervention MeSH terms: Afatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

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)