Afatinib in Subjects With Kidney Dysfunction
Primary Purpose
Renal Insufficiency
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Afatinib healthy
Afatinib severe renally impaired
Afatinib moderate renally impaired
Sponsored by
About this trial
This is an interventional treatment trial for Renal Insufficiency
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.
Sites / Locations
- 1200.216.1 Boehringer Ingelheim Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Other
Arm Label
Afatinib in moderate renal impaired
Afatinib in severe renal impaired
Afatinib in healthy subjects
Arm Description
Single Dose Afatinib in moderate renal impaired subjects
Single Dose Afatinib in severe renal impaired subjects
Single Dose Afatinib in healthy subjects matched by gender, race, age and BMI to moderate and severe renal impaired subjects
Outcomes
Primary Outcome Measures
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
Cmax of Afatinib (BIBW 2992)
Maximum measured concentration of the analyte in plasma
Secondary Outcome Measures
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02096718
Brief Title
Afatinib in Subjects With Kidney Dysfunction
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)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
May 2014 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Insufficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Afatinib in moderate renal impaired
Arm Type
Experimental
Arm Description
Single Dose Afatinib in moderate renal impaired subjects
Arm Title
Afatinib in severe renal impaired
Arm Type
Experimental
Arm Description
Single Dose Afatinib in severe renal impaired subjects
Arm Title
Afatinib in healthy subjects
Arm Type
Other
Arm Description
Single Dose Afatinib in healthy subjects matched by gender, race, age and BMI to moderate and severe renal impaired subjects
Intervention Type
Drug
Intervention Name(s)
Afatinib healthy
Intervention Type
Drug
Intervention Name(s)
Afatinib severe renally impaired
Intervention Type
Drug
Intervention Name(s)
Afatinib moderate renally impaired
Primary Outcome Measure Information:
Title
AUC 0-tz of Afatinib (BIBW 2992)
Description
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point
Time Frame
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
Title
Cmax of Afatinib (BIBW 2992)
Description
Maximum measured concentration of the analyte in plasma
Time Frame
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 Measure Information:
Title
AUC 0-inf of Afatinib (BIBW 2992)
Description
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
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
1200.216.1 Boehringer Ingelheim Investigational Site
City
Kiel
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
27436099
Citation
Wiebe S, Schnell D, Kulzer R, Gansser D, Weber A, Wallenstein G, Halabi A, Conrad A, Wind S. Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study. Eur J Drug Metab Pharmacokinet. 2017 Jun;42(3):461-469. doi: 10.1007/s13318-016-0359-9.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com/
Description
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Afatinib in Subjects With Kidney Dysfunction
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