Afatinib in Subjects With Kidney Dysfunction

NCT02096718 | Completed Phase 1 Results

• 2 other identifiers: 1200.2162013-004825-98
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Insufficiency

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (1)

• AUC 0-inf of Afatinib (BIBW 2992)

  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

Study Arms (3)

Afatinib in moderate renal impaired

EXPERIMENTAL

Single Dose Afatinib in moderate renal impaired subjects

Drug: Afatinib moderate renally impaired

Afatinib in severe renal impaired

EXPERIMENTAL

Single Dose Afatinib in severe renal impaired subjects

Drug: Afatinib severe renally impaired

Afatinib in healthy subjects

OTHER

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

Drug: Afatinib healthy

Interventions

Afatinib healthy DRUG

Afatinib in healthy subjects

Afatinib severe renally impaired DRUG

Afatinib in severe renal impaired

Afatinib moderate renally impaired DRUG

Afatinib in moderate renal impaired

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• to 59 mL/min for moderate renal impairment group 1
• to 29 mL/min for severe renal impairment group 2
• = 90 mL/min for healthy volunteers group 3
• Age =18 and =79 years

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1200.216.1 Boehringer Ingelheim Investigational Site

Kiel, Germany

Location

Related Publications (1)

• 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.

  PMID: 27436099 DERIVED

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Limitations and Caveats

Two healthy volunteers were matched to 2 different groups i.e. subjects with moderate renal impairment and subjects with severe renal impairment.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2014
• First Posted: March 26, 2014
• Study Start: May 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 14, 2016
• Results First Posted: January 14, 2016

Record last verified: 2015-11

Locations

DE (1)