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

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:

MedlinePlus related topics: Liver Diseases

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

AUC0-8 (area under the concentration time curve of afatinib in plasma over the time interval from 0 extrapolated to infinity) [ Time Frame: 11 days ] [ Designated as safety issue: No ]
Cmax (maximum concentration of afatinib in plasma) [ Time Frame: 11 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

AUC0-tz (area under the concentration-time curve of afatinib in plasma over the time interval from 0 to the time of the last quantifiable data point) [ Time Frame: 11 days ] [ Designated as safety issue: No ]
Safety and tolerability of afatinib by physical examination, vital signs, 12-lead electrocardiogram,clinical laboratory test (including hematology, clinical chemistry, coagulation, urinalysis) adverse event, investigator's global tolerability [ Time Frame: 28 days ] [ Designated as safety issue: No ]

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:

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)

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 Pharmaceuticals

Investigators

Study Chair:

Boehringer Ingelheim

Boehringer Ingelheim Pharmaceuticals

More Information

No publications provided

Responsible Party:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01298063 History of Changes
Other Study ID Numbers:	1200.86, 2010-021140-18
Study First Received:	February 15, 2011
Last Updated:	May 2, 2012
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 May 22, 2013