Back to results

Afatinib in Subjects With Kidney Dysfunction

Primary Purpose

Renal Insufficiency

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

Afatinib healthy

Afatinib severe renally impaired

Afatinib moderate renally impaired

About this trial

This is an interventional treatment trial for Renal Insufficiency

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesAccepts 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.

Sites / Locations

1200.216.1 Boehringer Ingelheim Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Other

Arm Label

Afatinib in moderate renal impaired

Afatinib in severe renal impaired

Afatinib in healthy subjects

Arm Description

Single Dose Afatinib in moderate renal impaired subjects

Single Dose Afatinib in severe renal impaired subjects

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

Outcomes

Primary Outcome Measures

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

Cmax of Afatinib (BIBW 2992)

Maximum measured concentration of the analyte in plasma

Secondary Outcome Measures

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

Full Information

NCT ID

NCT02096718

First Posted

March 24, 2014

Last Updated

December 9, 2015

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT02096718

Brief Title

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

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Completed

Study Start Date

May 2014 (undefined)

Primary Completion Date

December 2014 (Actual)

Study Completion Date

December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Insufficiency

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Afatinib in moderate renal impaired

Arm Type

Experimental

Arm Description

Single Dose Afatinib in moderate renal impaired subjects

Arm Title

Afatinib in severe renal impaired

Arm Type

Experimental

Arm Description

Single Dose Afatinib in severe renal impaired subjects

Arm Title

Afatinib in healthy subjects

Arm Type

Other

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Afatinib healthy

Intervention Type

Drug

Intervention Name(s)

Afatinib severe renally impaired

Intervention Type

Drug

Intervention Name(s)

Afatinib moderate renally impaired

Primary Outcome Measure Information:

Title

AUC 0-tz of Afatinib (BIBW 2992)

Description

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

Title

Cmax of Afatinib (BIBW 2992)

Description

Maximum measured concentration of the analyte in plasma

Time Frame

Secondary Outcome Measure Information:

Title

AUC 0-inf of Afatinib (BIBW 2992)

Description

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

79 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Organizational Affiliation

Boehringer Ingelheim

Official's Role

Study Chair

Facility Information:

Facility Name

1200.216.1 Boehringer Ingelheim Investigational Site

City

Kiel

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

27436099

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.

Results Reference

derived

Links:

URL

http://trials.boehringer-ingelheim.com/

Description

Related Info

Learn more about this trial

Afatinib in Subjects With Kidney Dysfunction

We'll reach out to this number within 24 hrs