Afatinib in Subjects With Kidney Dysfunction

Renal Insufficiency Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02096718
• Other study ID #: 1200.216
• Secondary ID: 2013-004825-98
• Status: Completed
• Phase: Phase 1
• First received: March 24, 2014
• Last updated: December 9, 2015
• Start date: May 2014
• Est. completion date: December 2014

Study information

• Verified date: November 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Insufficiency

Intervention

Drug:
• Afatinib healthy

• Afatinib severe renally impaired

• Afatinib moderate renally impaired

Locations

Country	Name	City	State
Germany	1200.216.1 Boehringer Ingelheim Investigational Site	Kiel

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	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	No
Primary	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	No
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	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	No

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