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

NCT01298063 | Completed Phase 1 Results

• 2 other identifiers: 1200.862010-021140-18
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Diseases; Healthy

Outcome Measures

Primary Outcomes (2)

• 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

  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

• Maximum Concentration (Cmax)

  Cmax represents the maximum measured concentration of the analyte in plasma

  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 Outcomes (2)

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

  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

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

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

Study Arms (3)

Afatinib Group A, B (2), D

EXPERIMENTAL

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

Drug: Afatinib

Afatinib Group B (3), D

EXPERIMENTAL

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

Drug: Afatinib

Afatinib Group B (1), D

EXPERIMENTAL

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

Drug: Afatinib

Interventions

Afatinib DRUG

1 tablet, once qd in the morning

Afatinib Group A, B (2), D

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Any relevant deviation from healthy conditions (excluded conditions caused by liver impairment)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1200.86.1 Boehringer Ingelheim Investigational Site

Kiel, Germany

Location

MeSH Terms

Conditions

Liver Diseases

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Digestive System Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2011
• First Posted: February 17, 2011
• Study Start: February 1, 2011
• Primary Completion: January 1, 2012
• Last Updated: December 31, 2013
• Results First Posted: October 17, 2013

Record last verified: 2013-08

Locations

DE (1)