Afatinib in Subjects With Kidney Dysfunction

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Renal Insufficiency

Treatments: Drug: Afatinib healthy; Drug: Afatinib moderate renally impaired; Drug: Afatinib severe renally impaired

Study type: Interventional

Funder types: Industry

Identifiers

NCT02096718

1200.216

2013-004825-98 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Afatinib in moderate renal impaired

Experimental group

Description:

Single Dose Afatinib in moderate renal impaired subjects

Treatment:

Drug: Afatinib moderate renally impaired

Afatinib in severe renal impaired

Experimental group

Description:

Single Dose Afatinib in severe renal impaired subjects

Treatment:

Drug: Afatinib severe renally impaired

Afatinib in healthy subjects

Other group

Description:

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

Treatment:

Drug: Afatinib healthy