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CompletedNCT02096718Updated Jan 14, 2016Results posted

Afatinib in Subjects With Kidney Dysfunction

A Phase 1 interventional study of Afatinib healthy and Afatinib severe renally impaired in Renal Insufficiency, sponsored by Boehringer Ingelheim. Completed at 1 site in Germany. Open to participants aged 18 Years to 79 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-01-14.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
30
Allocation
Non-randomized
Ages
18 Years to 79 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Renal Insufficiency

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03

In context

Renal Insufficiency

1,995 studies on the registry are indexed under Renal Insufficiency; 173 are open to participants now.

This study's enrollment of 30 is below the median of 43 across 1,504 interventional studies indexed under Renal Insufficiency.

Browse Renal Insufficiency studies →

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 79 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    Afatinib in moderate renal impaired

    Single Dose Afatinib in moderate renal impaired subjects

    Drug: Afatinib moderate renally impaired

  • Experimental
    Afatinib in severe renal impaired

    Single Dose Afatinib in severe renal impaired subjects

    Drug: Afatinib severe renally impaired

  • Other
    Afatinib in healthy subjects

    Single Dose Afatinib in healthy subjects matched by gender, race, age and BMI to moderate and severe renal impaired subjects

    Drug: Afatinib healthy

Interventions

  • DrugAfatinib healthy
  • DrugAfatinib severe renally impaired
  • DrugAfatinib moderate renally impaired
06

What researchers measure

Primary outcomes

  1. 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

    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

  2. Cmax of Afatinib (BIBW 2992)

    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 outcomes

  1. 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

    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

07

Results

Posted Jan 14, 2016
Limitations and caveats
Two healthy volunteers were matched to 2 different groups i.e. subjects with moderate renal impairment and subjects with severe renal impairment.

Participant flow

30 patients were entered, treated and analyzed.

Participant flow — Overall Study
MilestoneAfatinib in Moderate Renal ImpairmentAfatinib in Severe Renal ImpairmentAfatinib in Healthy Subjects
Started8814
Completed8814
Not completed000

Outcome measures

PrimaryAUC 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

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
Reported as:
Geometric mean · ng*h/mL
AUC 0-tz of Afatinib (BIBW 2992)
ng*h/mLAfatinib in Moderate Renal ImpairmentAfatinib in Severe Renal ImpairmentAfatinib in Healthy Subjects Matched to ModerateAfatinib in Healthy Subjects Matched to Severe
AUC 0-tz of Afatinib (BIBW 2992)948 ± 32.9952 ± 31.3776 ± 22.9634 ± 50.8
Statistical analysis
  • Afatinib in Moderate Renal Impairment vs Afatinib in Healthy Subjects Matched to Moderate · ANOVA · Ratio of gmeans: 122.23 · 90% CI 95.743 to 156.045Relative bioavailability comparison of afatinib for moderate vs. normal matched with moderate patients was estimated by the ratios of the geometric means (gMean). Standard deviation is actually Inter individual geometric coefficient variation (gCV).
  • Afatinib in Severe Renal Impairment vs Afatinib in Healthy Subjects Matched to Severe · ANOVA · Ratio of gmeans: 149.97 · 90% CI 105.266 to 213.671Relative 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).
PrimaryCmax of Afatinib (BIBW 2992)

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
Reported as:
Geometric mean · ng/mL
Cmax of Afatinib (BIBW 2992)
ng/mLAfatinib in Moderate Renal ImpairmentAfatinib in Severe Renal ImpairmentAfatinib in Healthy Subjects Matched to ModerateAfatinib in Healthy Subjects Matched to Severe
Cmax of Afatinib (BIBW 2992)28.7 ± 44.028.2 ± 24.528.3 ± 32.223.2 ± 42.1
Statistical analysis
  • Afatinib in Moderate Renal Impairment vs Afatinib in Healthy Subjects Matched to Moderate · ANOVA · Ratio of gmeans: 101.16 · 90% CI 72.931 to 140.309Relative bioavailability comparison of afatinib for moderate vs. normal matched with moderate patients was estimated by the ratios of the geometric means (gMean). Standard deviation is actually Inter individual geometric coefficient variation (gCV).
  • Afatinib in Severe Renal Impairment vs Afatinib in Healthy Subjects Matched to Severe · ANOVA · Ratio of gmeans: 121.71 · 90% CI 90.790 to 163.162Relative 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).
SecondaryAUC 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

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
Reported as:
Geometric mean · ng*h/mL
AUC 0-inf of Afatinib (BIBW 2992)
ng*h/mLAfatinib in Moderate Renal ImpairmentAfatinib in Severe Renal ImpairmentAfatinib in Healthy Subjects Matched to ModerateAfatinib in Healthy Subjects Matched to Severe
AUC 0-inf of Afatinib (BIBW 2992)976 ± 32.5980 ± 31.9797 ± 22.7653 ± 49.8
Statistical analysis
  • Afatinib in Moderate Renal Impairment vs Afatinib in Healthy Subjects Matched to Moderate · ANOVA · Ratio of gmeans: 122.44 · 90% CI 96.141 to 155.928Relative bioavailability comparison of afatinib for moderate vs. normal matched with moderate patients was estimated by the ratios of the geometric means (gMean). Standard deviation is actually Inter individual geometric coefficient variation (gCV).
  • Afatinib in Severe Renal Impairment vs Afatinib in Healthy Subjects Matched to Severe · ANOVA · Ratio of gmeans: 150.08 · 90% CI 105.626 to 213.250Relative 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).

Adverse events

Collected over From first administration of trial medication until the end of trial examination, up to 17 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Afatinib in Healthy Subjects—0/14 (0%)4/14 (28.6%)
Afatinib in Moderate Renal Impairment—0/8 (0%)2/8 (25%)
Afatinib in Severe Renal Impairment—0/8 (0%)0/8 (0%)
Most frequent other events
Most frequent other events
EventAfatinib in Healthy SubjectsAfatinib in Moderate Renal ImpairmentAfatinib in Severe Renal Impairment
DiarrhoeaGastrointestinal disorders1/141/80/8
NauseaGastrointestinal disorders0/141/80/8
VomitingGastrointestinal disorders0/141/80/8
HeadacheNervous system disorders1/140/80/8
SciaticaNervous system disorders1/140/80/8
PhlebitisVascular disorders1/140/80/8

Baseline characteristics

(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)

Age, Continuous
Age, Continuous(Years)Afatinib in Moderate Renal ImpairmentAfatinib in Severe Renal ImpairmentAfatinib in Healthy SubjectsTotal
Mean68.6 ± 11.061.0 ± 11.962.1 ± 11.463.6 ± 11.5
Sex: Female, Male
Sex: Female, Male(Participants)Afatinib in Moderate Renal ImpairmentAfatinib in Severe Renal ImpairmentAfatinib in Healthy SubjectsTotal
Female52714
Male36716
08

Study locations

1 site
  • 1200.216.1 Boehringer Ingelheim Investigational Site
    Kiel, Germany
09

References and documents

Publications

  • 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. PubMed 27436099 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 14, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02096718
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Mar 26, 2014
Start date
May 2014
Primary completion
Dec 2014
Completion
Dec 2014
Results posted
Jan 14, 2016
Last update
Jan 14, 2016

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim
View the source record on ClinicalTrials.gov ↗

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