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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004825-98 | EudraCT Number | EudraCT |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Afatinib in moderate renal impaired | Experimental | Single Dose Afatinib in moderate renal impaired subjects |
|
| Afatinib in severe renal impaired | Experimental | Single Dose Afatinib in severe renal impaired subjects |
|
| Afatinib in healthy subjects | Other | Single Dose Afatinib in healthy subjects matched by gender, race, age and BMI to moderate and severe renal impaired subjects |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Afatinib healthy | Drug |
| ||
| Afatinib severe renally impaired |
| 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 |
| 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 |
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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:
Age =18 and =79 years
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1200.216.1 Boehringer Ingelheim Investigational Site | Kiel | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27436099 | Derived | 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. |
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This was a non-randomised, non-controlled, open-label, single-dose trial with matched group design. Group 1 contained subjects with moderate renal impairment, Group 2 subjects with severe renal impairment, and Group 3 subjects with normal renal function; groups were dosed sequentially.
30 patients were entered, treated and analyzed.
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| ID | Title | Description |
|---|---|---|
| FG000 | Afatinib in Moderate Renal Impairment | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to moderately renally impaired subjects in fasted state with 240 mL of water |
| FG001 | Afatinib in Severe Renal Impairment | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to severely renally impaired subjects in fasted state with 240 mL of water |
| FG002 | Afatinib in Healthy Subjects | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to moderate and severe renal impaired subjects |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
(Treated Set) All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment. All 30 subjects were included in the treated set (TS)
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| ID | Title | Description |
|---|---|---|
| BG000 | Afatinib in Moderate Renal Impairment | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to moderately renally impaired subjects in fasted state with 240 mL of water |
| BG001 | Afatinib in Severe Renal Impairment |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | The pharmacokinetic set (PKS): included all patients in the treated set who provided evaluable data for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
From first administration of trial medication until the end of trial examination, up to 17 days
The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Afatinib in Healthy Subjects | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to moderate and severe renal impaired subjects |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
Two healthy volunteers were matched to 2 different groups i.e. subjects with moderate renal impairment and subjects with severe renal impairment.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| Drug |
|
| Afatinib moderate renally impaired | Drug |
|
Single Dose of 40 mg Afatinib film-coated tablet was orally administered to severely renally impaired subjects in fasted state with 240 mL of water
| BG002 | Afatinib in Healthy Subjects | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to moderate and severe renal impaired subjects |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Afatinib in Severe Renal Impairment | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to severely renally impaired subjects in fasted state with 240 mL of water |
| OG002 | Afatinib in Healthy Subjects Matched to Moderate | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to moderate renal impaired subjects |
| OG003 | Afatinib in Healthy Subjects Matched to Severe | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to severe renal impaired subjects |
|
|
|
| Primary | Cmax of Afatinib (BIBW 2992) | Maximum measured concentration of the analyte in plasma | The pharmacokinetic set (PKS): included all patients in the treated set who provided evaluable data for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 | 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 | The pharmacokinetic set (PKS): included all patients in the treated set who provided evaluable data for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
|
|
|
| 0 |
| 14 |
| 4 |
| 14 |
| EG001 | Afatinib in Moderate Renal Impairment | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to moderately renally impaired subjects in fasted state with 240 mL of water | 0 | 8 | 2 | 8 |
| EG002 | Afatinib in Severe Renal Impairment | Single Dose of 40 mg Afatinib film-coated tablet was orally administered to severely renally impaired subjects in fasted state with 240 mL of water | 0 | 8 | 0 | 8 |
| Nausea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| No |
| Superiority or Other |
| The ANOVA model was fitted using log-transformed values. The difference between the expected means of each comparison was estimated by the difference in the corresponding Least Square Means (point estimate), and 2-sided 90% confidence intervals based on the t-distribution. These quantities were then back-transformed to the original scale to give the point estimator (gMean), and interval estimates for the intersubject ratio of the gMeans for each renal function group. | ANOVA | Ratio of gmeans | 121.71 | Standard Deviation | 34.2 | 2-Sided | 90 | 90.790 | 163.162 | Relative bioavailability comparison of afatinib for severe vs. normal matched with severe patients was estimated by the ratios of the geometric means (gMean). Standard deviation is actually Inter individual geometric coefficient variation (gCV). | No | Superiority or Other |
| No |
| Superiority or Other |
| The ANOVA model was fitted using log-transformed values. The difference between the expected means of each comparison was estimated by the difference in the corresponding Least Square Means (point estimate), and 2-sided 90% confidence intervals based on the t-distribution. These quantities were then back-transformed to the original scale to give the point estimator (gMean), and interval estimates for the intersubject ratio of the gMeans for each renal function group. | ANOVA | Ratio of gmeans | 150.08 | Standard Deviation | 41.5 | 2-Sided | 90 | 105.626 | 213.250 | Relative bioavailability comparison of afatinib for severe vs. normal matched with severe patients was estimated by the ratios of the geometric means (gMean). Standard deviation is actually Inter individual geometric coefficient variation (gCV). | No | Superiority or Other |