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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01298063
First received: February 15, 2011
Last updated: December 5, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Liver Diseases
Healthy
Drug: Afatinib
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Area Under Curve From 0 to Infinity (AUC0-infinity) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity

  • Maximum Concentration (Cmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Cmax represents the maximum measured concentration of the analyte in plasma


Secondary Outcome Measures:
  • Area Under Curve From 0 to tz (AUC0-tz) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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

  • Clinical Relevant Abnormalitites for Physical Examination, Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Adverse Event, Investigator's Global Tolerability [ Time Frame: First administration of trial medication until 28 days after last administration of trial medication ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: February 2011
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Afatinib
1 tablet, once qd in the morning
Experimental: Afatinib Group B (3), D
healthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the medium dose of afatinib
Drug: Afatinib
1 tablet, once qd in the morning
Experimental: Afatinib Group B (1), D
healthy subjects, moderate liver impaired subjects to receive one single dose treatment containing the low dose of afatinib
Drug: Afatinib
1 tablet, once qd in the morning

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01298063

Locations
Germany
1200.86.1 Boehringer Ingelheim Investigational Site
Kiel, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01298063     History of Changes
Other Study ID Numbers: 1200.86, 2010-021140-18
Study First Received: February 15, 2011
Results First Received: August 8, 2013
Last Updated: December 5, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on April 21, 2014