Back to results

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

Primary Purpose

Liver Diseases, Healthy

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

Afatinib

About this trial

This is an interventional treatment trial for Liver Diseases

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

1200.86.1 Boehringer Ingelheim Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Afatinib Group A, B (2), D

Afatinib Group B (3), D

Afatinib Group B (1), D

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Area Under Curve From 0 to Infinity (AUC0-infinity)

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)

Cmax represents the maximum measured concentration of the analyte in plasma

Secondary Outcome Measures

Area Under Curve From 0 to tz (AUC0-tz)

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

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.

Full Information

NCT ID

NCT01298063

First Posted

February 15, 2011

Last Updated

December 5, 2013

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT01298063

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Completed

Study Start Date

February 2011 (undefined)

Primary Completion Date

January 2012 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Diseases, Healthy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

35 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Afatinib Group A, B (2), D

Arm Type

Experimental

Arm Description

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

Arm Title

Afatinib Group B (3), D

Arm Type

Experimental

Arm Description

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

Arm Title

Afatinib Group B (1), D

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Afatinib

Intervention Description

1 tablet, once qd in the morning

Intervention Type

Drug

Intervention Name(s)

Afatinib

Intervention Description

1 tablet, once qd in the morning

Intervention Type

Drug

Intervention Name(s)

Afatinib

Intervention Description

1 tablet, once qd in the morning

Primary Outcome Measure Information:

Title

Area Under Curve From 0 to Infinity (AUC0-infinity)

Description

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

Title

Maximum Concentration (Cmax)

Description

Cmax represents the maximum measured concentration of the analyte in plasma

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

Secondary Outcome Measure Information:

Title

Area Under Curve From 0 to tz (AUC0-tz)

Description

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

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

Title

Clinical Relevant Abnormalitites for Physical Examination, Vital Signs, 12-lead ECG, Clinical Laboratory Tests, Adverse Event, Investigator's Global Tolerability

Description

Time Frame

First administration of trial medication until 28 days after last administration of trial medication

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Organizational Affiliation

Boehringer Ingelheim

Official's Role

Study Chair

Facility Information:

Facility Name

1200.86.1 Boehringer Ingelheim Investigational Site

City

Kiel

Country

Germany

12. IPD Sharing Statement

Links:

URL

http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1200/1200.86_U12-1171-01.pdf

Description

Related Info

URL

http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1200/1200.86_Literature.pdf

Description

Related Info

Learn more about this trial

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

We'll reach out to this number within 24 hrs