Clinical trial NCT02096718: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Insufficiency
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-03-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: AUC 0-tz of Afatinib (BIBW 2992)
timeFrame: 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: Cmax of Afatinib (BIBW 2992)
timeFrame: 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:
measure: AUC 0-inf of Afatinib (BIBW 2992)
timeFrame: 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
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: 1200.216.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
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.