Drug Interaction Study With Rifampicin and Afatinib

Study Overview
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Brief Summary
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The objective of the current study is to investigate the effect of the P-gp inducer rifampicin on the pharmacokinetics (PK) of afatinib in healthy male volunteers

Official Title
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Relative Bioavailability of a Single Oral Dose of 40 mg Afatinib Given Alone and After Multiple Doses of Rifampicin - an Open-label, Two-period, Fixed Sequence Clinical Phase I Trial in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Afatinib
* Drug: Afatinib
* Drug: Rifampicin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male volunteers Exclusion criteria: Any relevant deviations from healthy conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afatinib alone (Reference)<br>Tablet, Oral administration with 240 mL of water | Drug: Afatinib<br>* single dose<br>|
| Experimental: Rifampicin + Afatinib (Test)<br>Tablet, Oral administration with 240 mL of water | Drug: Afatinib<br>* single dose<br>Drug: Rifampicin<br>* multiple doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under Curve From 0 to Infinity Hours (AUC0-∞) | AUC0-∞ represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | 
| Area Under Curve From 0 to tz (AUC0-tz) | AUC0-tz represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | 
| Maximum Concentration (Cmax) | Cmax represents the maximum concentration of the analyte in plasma. | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Dosing to the Maximum Concentration of Afatinib in Plasma (Tmax) | tmax represents the time from dosing to the maximum concentration of the analyte in plasma | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | 
| Terminal Half-life of Afatinib in Plasma (t1/2) | t1/2 represents the terminal half-life of the analyte in plasma | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | 
| Area Under Curve From 0 to 24 h (AUC0-24) | AUC0-24 represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours (h) | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | 
| Percentage of the AUCtz-∞ Obtained by Extrapolation (%AUCtz-∞) | %AUCtz-∞ represents the percentage of the AUCtz-∞ obtained by extrapolation | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | 
| Mean Residence Time of Afatinib in the Body After Oral Administration (MRTpo) | MRTpo represents the mean residence time of the analyte in the body after oral administration | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | 
| Apparent Clearance of Afatinib in the Plasma After Extravascular Administration (CL/F) | CL/F represents the apparent clearance of the analyte in the plasma after extravascular administration | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose | 
| Apparent Volume of Distribution During the Terminal Phase lambda_z Following an Extravascular Dose (V_z/F) | V_z/F represents the apparent volume of distribution during the terminal phase λz following an extravascular dose | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |