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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-001804-37 | EudraCT Number | EudraCT |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Afatinib alone (Reference) | Experimental | Tablet, Oral administration with 240 mL of water |
|
| Rifampicin + Afatinib (Test) | Experimental | Tablet, Oral administration with 240 mL of water |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Afatinib | Drug | single dose |
| |
| Afatinib |
| 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 |
| 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) |
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Inclusion criteria:
Healthy male volunteers
Exclusion criteria:
Any relevant deviations from healthy conditions
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1200.152.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
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| ID | Title | Description |
|---|---|---|
| FG000 | Overall Group | Subjects were treated with a single morning dose of Afatinib 40mg on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Afatinib |
| |||||||||||||
| Washout |
| |||||||||||||
| Rifa+Afatinib |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study | This was a open-label, two period, fixed sequence trial clinical phase I trial in healthy male volunteers. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |
|
First administration of trial medication until 6 days after last administration of trial medication
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Afatinib | Subjects were treated with a single morning dose of Afatinib 40mg on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D000077716 | Afatinib |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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| Drug |
single dose |
|
| Rifampicin | Drug | multiple doses |
|
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 |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Afatinib + Rifa |
Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1. |
|
|
|
| Primary | 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. | PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |
|
|
|
|
| Primary | Maximum Concentration (Cmax) | Cmax represents the maximum concentration of the analyte in plasma. | PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |
|
|
|
|
| Secondary | 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 | PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib. | Posted | Median | Full Range | hours | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |
|
|
|
| Secondary | Terminal Half-life of Afatinib in Plasma (t1/2) | t1/2 represents the terminal half-life of the analyte in plasma | PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |
|
|
|
| Secondary | 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) | PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |
|
|
|
| Secondary | Percentage of the AUCtz-∞ Obtained by Extrapolation (%AUCtz-∞) | %AUCtz-∞ represents the percentage of the AUCtz-∞ obtained by extrapolation | PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of AUCtz-∞ | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |
|
|
|
| Secondary | 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 | PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |
|
|
|
| Secondary | 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 | PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |
|
|
|
| Secondary | 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 | PK analysis set - all subjects of the treated set who provided at least 1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations relevant to the evaluation for PL, and who did not experience vomiting at or before 2 times median tmax for afatinib. | Posted | Geometric Mean | Geometric Coefficient of Variation | Litres | 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post dose |
|
|
|
| 0 |
| 22 |
| 2 |
| 22 |
| EG001 | Afatinib + Rifa | Subjects were treated with Rifa 600mg once daily (evening) from Day -7 to -1 and with a single morning dose of Afatinib 40mg on Day 1. | 0 | 22 | 4 | 22 |
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |