Trial Outcomes & Findings for Afatinib in Subjects With Kidney Dysfunction (NCT NCT02096718)

NCT ID: NCT02096718

Last Updated: 2016-01-14

Results Overview

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 30 participants
• Primary outcome 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
• Results posted on: 2016-01-14

Participant Flow

30 patients were entered, treated and analyzed.

This was a non-randomised, non-controlled, open-label, single-dose trial with matched group design. Group 1 contained subjects with moderate renal impairment, Group 2 subjects with severe renal impairment, and Group 3 subjects with normal renal function; groups were dosed sequentially.

Participant milestones

Measure	Afatinib in Moderate Renal Impairment Single Dose of 40 mg Afatinib film-coated tablet was orally administered to moderately renally impaired subjects in fasted state with 240 mL of water	Afatinib in Severe Renal Impairment Single Dose of 40 mg Afatinib film-coated tablet was orally administered to severely renally impaired subjects in fasted state with 240 mL of water	Afatinib in Healthy Subjects Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to moderate and severe renal impaired subjects
Overall Study STARTED	8	8	14
Overall Study COMPLETED	8	8	14
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Afatinib in Subjects With Kidney Dysfunction

Baseline characteristics by cohort

Measure	Afatinib in Moderate Renal Impairment n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to moderately renally impaired subjects in fasted state with 240 mL of water	Afatinib in Severe Renal Impairment n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to severely renally impaired subjects in fasted state with 240 mL of water	Afatinib in Healthy Subjects n=14 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to moderate and severe renal impaired subjects	Total n=30 Participants Total of all reporting groups
Age, Continuous	68.6 Years STANDARD_DEVIATION 11.0 • n=5 Participants	61.0 Years STANDARD_DEVIATION 11.9 • n=7 Participants	62.1 Years STANDARD_DEVIATION 11.4 • n=5 Participants	63.6 Years STANDARD_DEVIATION 11.5 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	16 Participants n=4 Participants

PRIMARY outcome

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

Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided evaluable data for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point

Outcome measures

Measure	Afatinib in Moderate Renal Impairment n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to moderately renally impaired subjects in fasted state with 240 mL of water	Afatinib in Severe Renal Impairment n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to severely renally impaired subjects in fasted state with 240 mL of water	Afatinib in Healthy Subjects Matched to Moderate n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to moderate renal impaired subjects	Afatinib in Healthy Subjects Matched to Severe n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to severe renal impaired subjects
AUC 0-tz of Afatinib (BIBW 2992)	948 ng*h/mL Geometric Coefficient of Variation 32.9	952 ng*h/mL Geometric Coefficient of Variation 31.3	776 ng*h/mL Geometric Coefficient of Variation 22.9	634 ng*h/mL Geometric Coefficient of Variation 50.8

PRIMARY outcome

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

Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided evaluable data for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.

Maximum measured concentration of the analyte in plasma

Outcome measures

Measure	Afatinib in Moderate Renal Impairment n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to moderately renally impaired subjects in fasted state with 240 mL of water	Afatinib in Severe Renal Impairment n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to severely renally impaired subjects in fasted state with 240 mL of water	Afatinib in Healthy Subjects Matched to Moderate n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to moderate renal impaired subjects	Afatinib in Healthy Subjects Matched to Severe n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to severe renal impaired subjects
Cmax of Afatinib (BIBW 2992)	28.7 ng/mL Geometric Coefficient of Variation 44.0	28.2 ng/mL Geometric Coefficient of Variation 24.5	28.3 ng/mL Geometric Coefficient of Variation 32.2	23.2 ng/mL Geometric Coefficient of Variation 42.1

SECONDARY outcome

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

Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided evaluable data for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.

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

Outcome measures

Measure	Afatinib in Moderate Renal Impairment n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to moderately renally impaired subjects in fasted state with 240 mL of water	Afatinib in Severe Renal Impairment n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to severely renally impaired subjects in fasted state with 240 mL of water	Afatinib in Healthy Subjects Matched to Moderate n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to moderate renal impaired subjects	Afatinib in Healthy Subjects Matched to Severe n=8 Participants Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to severe renal impaired subjects
AUC 0-inf of Afatinib (BIBW 2992)	976 ng*h/mL Geometric Coefficient of Variation 32.5	980 ng*h/mL Geometric Coefficient of Variation 31.9	797 ng*h/mL Geometric Coefficient of Variation 22.7	653 ng*h/mL Geometric Coefficient of Variation 49.8

Adverse Events

Afatinib in Healthy Subjects

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Afatinib in Moderate Renal Impairment

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Afatinib in Severe Renal Impairment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Afatinib in Healthy Subjects n=14 participants at risk Single Dose of 40 mg Afatinib film-coated tablet was orally administered to healthy subjects in fasted state with 240 mL of water; healthy subjects were matched by gender, race, age and BMI to moderate and severe renal impaired subjects	Afatinib in Moderate Renal Impairment n=8 participants at risk Single Dose of 40 mg Afatinib film-coated tablet was orally administered to moderately renally impaired subjects in fasted state with 240 mL of water	Afatinib in Severe Renal Impairment n=8 participants at risk Single Dose of 40 mg Afatinib film-coated tablet was orally administered to severely renally impaired subjects in fasted state with 240 mL of water
Gastrointestinal disorders Diarrhoea	7.1% 1/14 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	12.5% 1/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	0.00% 0/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.
Gastrointestinal disorders Nausea	0.00% 0/14 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	12.5% 1/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	0.00% 0/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.
Gastrointestinal disorders Vomiting	0.00% 0/14 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	12.5% 1/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	0.00% 0/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.
Nervous system disorders Headache	7.1% 1/14 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	0.00% 0/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	0.00% 0/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.
Nervous system disorders Sciatica	7.1% 1/14 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	0.00% 0/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	0.00% 0/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.
Vascular disorders Phlebitis	7.1% 1/14 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	0.00% 0/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.	0.00% 0/8 • From first administration of trial medication until the end of trial examination, up to 17 days The residual effect period (REP) for afatinib in subjects with renal impairment (that is, the time period in which measurable drug levels were still likely to be present) was 17 days. Therefore, all AEs reported within 17 days of afatinib administration were to be considered as occurring on treatment.

Additional Information

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Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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