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OpenTrials
Completed

NCT Number: NCT01298063

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

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.

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Key information

Conditions

Liver Diseases Digestive System Diseases Healthy

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

1200.86.1 Boehringer Ingelheim Investigational Site

Kiel, Germany

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

afatinib

Drug

1 tablet, once qd in the morning

Primary outcomes

  1. 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

    AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity

  2. 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

    Cmax represents the maximum measured concentration of the analyte in plasma

Secondary outcomes

  1. 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

    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

  2. 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

    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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2012
First posted
Feb 17, 2011
Registry last updated
Dec 31, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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