Afatinib in Subjects With Kidney Dysfunction

• ClinicalTrials.gov Identifier: NCT02096718
• Recruitment Status: Completed
• First Posted: March 26, 2014
• Results First Posted: January 14, 2016
• Last Update Posted: January 14, 2016
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

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.

Condition or disease	Intervention/treatment	Phase
Renal Insufficiency	Drug: Afatinib healthy; Drug: Afatinib severe renally impaired; Drug: Afatinib moderate renally impaired	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: May 2014
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: December 2014

Arms and Interventions

Arm	Intervention/treatment
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
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

Outcome Measures

Primary Outcome Measures :

1. AUC 0-tz of Afatinib (BIBW 2992) [ 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 ]
   Area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point
2. Cmax of Afatinib (BIBW 2992) [ 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 ]
   Maximum measured concentration of the analyte in plasma

Secondary Outcome Measures :

1. AUC 0-inf of Afatinib (BIBW 2992) [ 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 ]
   Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Germany

1200.216.1 Boehringer Ingelheim Investigational Site

Kiel, Germany

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wiebe S, Schnell D, Külzer 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.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02096718
• Other Study ID Numbers: 1200.216; 2013-004825-98 ( EudraCT Number: EudraCT )
• First Posted: March 26, 2014
• Results First Posted: January 14, 2016
• Last Update Posted: January 14, 2016
• Last Verified: November 2015

Additional relevant MeSH terms:

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Afatinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action