Afatinib in Subjects With Kidney Dysfunction

Study Overview
=================
Brief Summary
-----------------
The primary objective of the current study is to investigate the influence of moderate to severe renal impairment on the pharmacokinetics and safety of a single dose afatinib in comparison to a control group with normal renal function. The assessment of safety and tolerability will be an additional objective of this trial and will be evaluated by descriptive statistics.

Official Title
-----------------
Pharmacokinetics, Safety and Tolerability After Single Dose Administration of Afatinib in Moderate and Severe Renal Impairment in Comparison to Subjects With Normal Renal Function (a Mono-centric, Open-label Study in Matched-group Design)

Conditions
-----------------
Renal Insufficiency

Intervention / Treatment
-----------------
* Drug: Afatinib healthy
* Drug: Afatinib severe renally impaired
* Drug: Afatinib moderate renally impaired


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Despite renal impairment (group 1 and 2) healthy males or females according to the investigators assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests. Glomerular filtration rate (GFR), estimated according to: -- MDRD (Modification of Diet in Renal Disease)-formula: eGFR (estimated Glomerular Filtration Rate) [ml/min/1.73m²]= 175 x Serum Creatinine-1.154 x age-0.203 (if male) eGFR[ml/min/1.73m²]= 175 x Serum Creatinine-1.154 x age-0.203 x 0.742 (if female) 30 to 59 mL/min for moderate renal impairment group 1 15 to 29 mL/min for severe renal impairment group 2 = 90 mL/min for healthy volunteers group 3 Age =18 and =79 years Exclusion criteria: Any finding of the medical examination (including Blood Pressure (BP), Pulse Rate (PR) and Electrocardiogram (ECG)) deviating from normal and of clinical relevance, e.g. repeated measurement of systolic blood pressure < 90 mmHg (millimeter of mercury) or > 140 mmHg, diastolic blood pressure < 50 mmHg or > 90 mmHg, repeated measurement of pulse rate < 45 bpm (beats per minute) or > 90 bpm. Any evidence of a clinically relevant concomitant disease. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, dermatological or hormonal disorders. Relevant gastrointestinal tract surgery (except appendectomy). Diseases of the central nervous system (such as epilepsy, seizures) or psychiatric disorders or neurological disorders. History of photosensitivity or recurrent rash. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afatinib in moderate renal impaired<br>Single Dose Afatinib in moderate renal impaired subjects | Drug: Afatinib moderate renally impaired<br> <br> |
| Experimental: Afatinib in severe renal impaired<br>Single Dose Afatinib in severe renal impaired subjects | Drug: Afatinib severe renally impaired<br> <br> |
| Other: Afatinib in healthy subjects<br>Single Dose Afatinib in healthy subjects matched by gender, race, age and BMI to moderate and severe renal impaired subjects | Drug: Afatinib healthy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 0-tz of Afatinib (BIBW 2992) | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point | PK plasma samples were taken at: 1 hour before drug administration and 0.5 hour (h), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 312h after first drug administration | 
| Cmax of Afatinib (BIBW 2992) | Maximum measured concentration of the analyte in plasma | PK plasma samples were taken at: 1 hour before drug administration and 0.5 hour (h), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 312h after first drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 0-inf of Afatinib (BIBW 2992) | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity | PK plasma samples were taken at: 1 hour before drug administration and 0.5 hour (h), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 312h after first drug administration |