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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-020560-37 | EudraCT Number | EudraCT |
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To establish the maximum tolerated dose (MTD) of oral afatinib (BIBW2992) given in combination with gemcitabine or docetaxel in patients with relapsed or refractory tumors.
To assess the safety of the combination. To investigate the PK characteristics of docetaxel or gemcitabine and of oral afatinib (BIBW2992) in the tested treatment schedule. To assess antitumor activity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Afatinib and docetaxel |
| ||
| Afatinib and gemcitabine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Afatinib | Drug | Maximum Tolerated Dose of Afatinib in combination with gemcitabine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD). | DLT was based on following criterions: 1. Grade 4 uncomplicated (not associated with fever >38.5° C (Celsius)) neutropenia for ≥7 days. 2. Grade 3 or 4 neutropenia concomitant with fever >38.5º C or Grade ≥3 infection. 3. Platelet count of <25x 10^9/L or <50x 10^9/L with bleeding requiring whole blood transfusion. 4. Grade ≥3 non-haematological toxicity (except untreated nausea, untreated vomiting, or untreated diarrhoea). 5. Grade ≥2 decrease in cardiac left ventricular function. 6. Grade ≥2 worsening of renal function as measured by serum creatinine, newly developed proteinuria, or a newly developed decrease in glomerular filtration rate. Toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 | 3 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| The Incidence and Intensity of AEs With Grading According to CTCAE. | The incidence and intensity of adverse events with grading according to CTCAE. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE). | From first drug administration until 28 days after last drug administration, up to 717 days. |
Not provided
Inclusion criteria:
1. histologically or cytologically confirmed diagnosis of any advanced or metastatic relapsed or refractory solid tumor.
Exclusion criteria:
Not provided
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solid tumors
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1200.93.33002 Boehringer Ingelheim Investigational Site | Dijon | France | ||||
| 1200.93.33001 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29808308 | Derived | Hiret S, Isambert N, Gomez-Roca C, Bennouna J, Sassi M, de Mont-Serrat H, Fan J, Schnell D, Delord JP. Phase I dose-escalation trial of afatinib, an irreversible ErbB family blocker, in combination with gemcitabine or docetaxel in patients with relapsed or refractory solid tumors. Invest New Drugs. 2018 Dec;36(6):1044-1059. doi: 10.1007/s10637-018-0601-1. Epub 2018 May 29. |
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This was an uncontrolled, open-label, Phase I, '3+3' dose-escalation trial to determine the maximum tolerated dose (MTDs) for combination Afatinib with Gemcitabine or with Docetaxel; 2 MTDs were to be defined, one for Afatinib with Gemcitabine (Cohort A) and one for Afatinib with Docetaxel (Cohort B).
All patients were completed the study but discontinued from the trial medication
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| ID | Title | Description |
|---|---|---|
| FG000 | Afatinib 30mg and Gemcitabine 1000mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| FG001 | Afatinib 30mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| FG002 | Afatinib 40mg and Gemcitabine 1000mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| FG003 | Afatinib 40mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| FG004 | Afatinib 50mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| FG005 | Afatinib 30mg and Docetaxel 60mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 60 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course |
| FG006 | Afatinib 30mg and Docetaxel 75mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. |
| FG007 | Afatinib 40mg and Docetaxel 75mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. |
| FG008 | Afatinib 50mg and Docetaxel 75mg | Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated Set (TS): The Treated Set consists of all patients who received at least one application of the trial drug.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Afatinib 30mg and Gemcitabine 1000mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| BG001 | Afatinib 30mg and Gemcitabine 1250mg |
| 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 | Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD). | DLT was based on following criterions: 1. Grade 4 uncomplicated (not associated with fever >38.5° C (Celsius)) neutropenia for ≥7 days. 2. Grade 3 or 4 neutropenia concomitant with fever >38.5º C or Grade ≥3 infection. 3. Platelet count of <25x 10^9/L or <50x 10^9/L with bleeding requiring whole blood transfusion. 4. Grade ≥3 non-haematological toxicity (except untreated nausea, untreated vomiting, or untreated diarrhoea). 5. Grade ≥2 decrease in cardiac left ventricular function. 6. Grade ≥2 worsening of renal function as measured by serum creatinine, newly developed proteinuria, or a newly developed decrease in glomerular filtration rate. Toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 | Treated Set (TS) | Posted | Number | Participants | 3 weeks |
|
From first drug administration until 28 days after last drug administration, up to 717 days
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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 30mg and Gemcitabine 1000mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
Not provided
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000077716 | Afatinib |
| D000077143 | Docetaxel |
| D000093542 | Gemcitabine |
| ID | Term |
|---|---|
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
Not provided
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Pharmacokinetic samples
| Afatinib | Drug | Maximum Tolerated Dose of Afatinib in combination with gemcitabine |
|
| docetaxel | Drug | Maximum Tolerated Dose of Afatinib in combination with docetaxel |
|
| gemcitabine | Drug | Maximum Tolerated Dose of Afatinib in combination with gemcitabine |
|
| Best Overall Response According to RECIST v1.1 Criteria | Best overall response (according to Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) was the best response recorded at any time from the date of the first administration of afatinib or gemcitabine/docetaxel to the end of treatment (EOT). Partial response is for patients with measurable disease. Missing categories signifies that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed. | From first drug administration until 28 days after last drug administration, up to 717 days. |
| Disease Control According to RECIST v1.1 | Disease control according to RECIST v1.1 Disease control is complete response, partial response or stable disease for measurable patients and complete response or non-CR/non-PD for non-measurable patients. Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed. | From first drug administration until 28 days after last drug administration, up to 717 days. |
| Objective Response According to RECIST v1.1 | Objective response according to RECIST v1.1. Objective response is complete response or partial response for patients with measurable disease. Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed. | From first drug administration until 28 days after last drug administration, up to 717 days. |
| Time to Objective Response According to RECIST v1.1 | Objective response according to RECIST v1.1. Objective response is complete response or partial response for patients with measurable disease. Time to objective response is the time from the start of treatment to the date of first documented complete response or partial response. Descriptive analyses has been performed for the time to objective response (N(%) of patients with first occurrence of objective response at 6, 12 and 24 weeks). Onset of objective response is derived for patient with measurable disease. | 6 weeks, 12 weeks and 24 weeks |
| Duration of Objective Response According to RECIST v1.1 | Duration of objective response was the time from the first documented complete response or partial response to disease progression or death. | From the first documented complete response or partial response to the time of disease progression or death |
| Duration of Disease Control According to RECIST v1.1 | Duration of disease control according to RECIST v1.1. | From the first administration of study medication to the time of disease progression or death |
| Progression Free Survival (PFS) | Progression-free survival was defined as the time from the first administration of study medication to the time of disease progression or death, whichever occurred first. | From the first administration of study medication to the time of disease progression or death |
| Overall Survival (OS) | Overall survival was defined as the time from the first administration of study medication to the time of death from any cause. | From the first administration of study medication to the time of death |
| Area Under the Concentration-time Curve (AUC) Tau,ss of Afatinib | Area under the concentration-time curve of Afatinib in plasma over a uniform dosing interval t at steady state. | PK samples were taken at hours; 167:55, 479:55, 481:05, 482:05, 483:05, 485:05, 487:05 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
| Cmax,ss of Afatinib | Maximum concentration of Afatinib in plasma at steady state. | PK samples were taken at hours; 167:55, 479:55, 481:05, 482:05, 483:05, 485:05, 487:05 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
| AUC 0-tz of Gemcitabine | Area under the concentration-time curve of Gemcitabine in plasma over the time interval from 0 up to the last quantifiable data point | PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 |
| Cmax of Gemcitabine | Maximum concentration of Gemcitabine in plasma. | PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 |
| Total Clearance (CL) of Gemcitabine | Total Clearance (CL) of Gemcitabine from plasma. | PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 |
| Volume of Distribution at Steady State (Vss) of Gemcitabine | Apparent volume of distribution at steady state (Vss) of Gemcitabine. | PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 |
| AUC 0-24 of Docetaxel | Area under the concentration-time curve of docetaxel in plasma over the time interval from 0 up to 24 hours | PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
| Cmax of Docetaxel | Maximum concentration of docetaxel in plasma. | PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
| Total Clearance (CL) of Docetaxel | Total Clearance (CL) of Docetaxel from plasma. | PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
| Volume of Distribution at Steady State (Vss) of Docetaxel | Apparent volume of distribution at steady state (Vss) of Docetaxel. | PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
| Saint-Herblain |
| France |
| 1200.93.33003 Boehringer Ingelheim Investigational Site | Toulouse | France |
| Dose-limiting toxicity |
|
| Adverse Event |
|
| Withdrawal by Subject |
|
| Other reason not mentioned above |
|
Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| BG002 | Afatinib 40mg and Gemcitabine 1000mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| BG003 | Afatinib 40mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| BG004 | Afatinib 50mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| BG005 | Afatinib 30mg and Docetaxel 60mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 60 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course |
| BG006 | Afatinib 30mg and Docetaxel 75mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. |
| BG007 | Afatinib 40mg and Docetaxel 75mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. |
| BG008 | Afatinib 50mg and Docetaxel 75mg | Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. |
| BG009 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| OG001 | Afatinib 30mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| OG002 | Afatinib 40mg and Gemcitabine 1000mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| OG003 | Afatinib 40mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| OG004 | Afatinib 50mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. |
| OG005 | Afatinib 30mg and Docetaxel 60mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 60 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course |
| OG006 | Afatinib 30mg and Docetaxel 75mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. |
| OG007 | Afatinib 40mg and Docetaxel 75mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. |
| OG008 | Afatinib 50mg and Docetaxel 75mg | Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. |
|
|
| Secondary | The Incidence and Intensity of AEs With Grading According to CTCAE. | The incidence and intensity of adverse events with grading according to CTCAE. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE). | TS | Posted | Number | Participants | From first drug administration until 28 days after last drug administration, up to 717 days. |
|
|
|
| Secondary | Best Overall Response According to RECIST v1.1 Criteria | Best overall response (according to Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) was the best response recorded at any time from the date of the first administration of afatinib or gemcitabine/docetaxel to the end of treatment (EOT). Partial response is for patients with measurable disease. Missing categories signifies that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed. | TS | Posted | Number | Participants | From first drug administration until 28 days after last drug administration, up to 717 days. |
|
|
|
| Secondary | Disease Control According to RECIST v1.1 | Disease control according to RECIST v1.1 Disease control is complete response, partial response or stable disease for measurable patients and complete response or non-CR/non-PD for non-measurable patients. Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed. | TS | Posted | Number | Participants | From first drug administration until 28 days after last drug administration, up to 717 days. |
|
|
|
| Secondary | Objective Response According to RECIST v1.1 | Objective response according to RECIST v1.1. Objective response is complete response or partial response for patients with measurable disease. Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed. | TS | Posted | Number | Participants | From first drug administration until 28 days after last drug administration, up to 717 days. |
|
|
|
| Secondary | Time to Objective Response According to RECIST v1.1 | Objective response according to RECIST v1.1. Objective response is complete response or partial response for patients with measurable disease. Time to objective response is the time from the start of treatment to the date of first documented complete response or partial response. Descriptive analyses has been performed for the time to objective response (N(%) of patients with first occurrence of objective response at 6, 12 and 24 weeks). Onset of objective response is derived for patient with measurable disease. | TS | Posted | Number | Participants | 6 weeks, 12 weeks and 24 weeks |
|
|
|
| Secondary | Duration of Objective Response According to RECIST v1.1 | Duration of objective response was the time from the first documented complete response or partial response to disease progression or death. | TS for patients who experienced objective response. | Posted | Mean | Standard Deviation | Days | From the first documented complete response or partial response to the time of disease progression or death |
|
|
|
| Secondary | Duration of Disease Control According to RECIST v1.1 | Duration of disease control according to RECIST v1.1. | TS for patients who experienced disease control. | Posted | Mean | Standard Deviation | Days | From the first administration of study medication to the time of disease progression or death |
|
|
|
| Secondary | Progression Free Survival (PFS) | Progression-free survival was defined as the time from the first administration of study medication to the time of disease progression or death, whichever occurred first. | TS, MTD cohort | Posted | Median | Inter-Quartile Range | Weeks | From the first administration of study medication to the time of disease progression or death |
|
|
|
| Secondary | Overall Survival (OS) | Overall survival was defined as the time from the first administration of study medication to the time of death from any cause. | TS, MTD cohort | Posted | Median | Inter-Quartile Range | Weeks | From the first administration of study medication to the time of death |
|
|
|
| Secondary | Area Under the Concentration-time Curve (AUC) Tau,ss of Afatinib | Area under the concentration-time curve of Afatinib in plasma over a uniform dosing interval t at steady state. | The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | PK samples were taken at hours; 167:55, 479:55, 481:05, 482:05, 483:05, 485:05, 487:05 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
|
|
|
|
| Secondary | Cmax,ss of Afatinib | Maximum concentration of Afatinib in plasma at steady state. | The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | PK samples were taken at hours; 167:55, 479:55, 481:05, 482:05, 483:05, 485:05, 487:05 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
|
|
|
|
| Secondary | AUC 0-tz of Gemcitabine | Area under the concentration-time curve of Gemcitabine in plasma over the time interval from 0 up to the last quantifiable data point | The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 |
|
|
|
|
| Secondary | Cmax of Gemcitabine | Maximum concentration of Gemcitabine in plasma. | The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 |
|
|
|
|
| Secondary | Total Clearance (CL) of Gemcitabine | Total Clearance (CL) of Gemcitabine from plasma. | The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 |
|
|
|
| Secondary | Volume of Distribution at Steady State (Vss) of Gemcitabine | Apparent volume of distribution at steady state (Vss) of Gemcitabine. | The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 |
|
|
|
| Secondary | AUC 0-24 of Docetaxel | Area under the concentration-time curve of docetaxel in plasma over the time interval from 0 up to 24 hours | The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
|
|
|
|
| Secondary | Cmax of Docetaxel | Maximum concentration of docetaxel in plasma. | The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
|
|
|
|
| Secondary | Total Clearance (CL) of Docetaxel | Total Clearance (CL) of Docetaxel from plasma. | The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
|
|
|
| Secondary | Volume of Distribution at Steady State (Vss) of Docetaxel | Apparent volume of distribution at steady state (Vss) of Docetaxel. | The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 |
|
|
|
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Afatinib 30mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. | 3 | 8 | 8 | 8 |
| EG002 | Afatinib 40mg and Gemcitabine 1000mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. | 12 | 20 | 20 | 20 |
| EG003 | Afatinib 40mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. | 2 | 6 | 6 | 6 |
| EG004 | Afatinib 50mg and Gemcitabine 1250mg | Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course. | 2 | 2 | 2 | 2 |
| EG005 | Afatinib 30mg and Docetaxel 60mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 60 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. | 7 | 18 | 18 | 18 |
| EG006 | Afatinib 30mg and Docetaxel 75mg | Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. | 15 | 18 | 18 | 18 |
| EG007 | Afatinib 40mg and Docetaxel 75mg | Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. | 8 | 12 | 12 | 12 |
| EG008 | Afatinib 50mg and Docetaxel 75mg | Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course. | 6 | 6 | 6 | 6 |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Subileus | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Performance status decreased | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Bile duct stenosis | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hepatocellular injury | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Bacterial infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Escherichia infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Peritonitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Sepsis syndrome | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Sphingomonas paucimobilis infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Glomerular filtration rate decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypercreatininaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Trismus | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
|
| Metastases to meninges | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
|
| Metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
|
| Paraparesis | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pyelocaliectasis | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Ureteric stenosis | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Urinary bladder polyp | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Subclavian vein thrombosis | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Atrioventricular block first degree | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
|
| Left ventricular dysfunction | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
|
| Ichthyosis | Congenital, familial and genetic disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 18.0 | Systematic Assessment |
|
| Erythema of eyelid | Eye disorders | MedDRA 18.0 | Systematic Assessment |
|
| Eyelid irritation | Eye disorders | MedDRA 18.0 | Systematic Assessment |
|
| Eyelid oedema | Eye disorders | MedDRA 18.0 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA 18.0 | Systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA 18.0 | Systematic Assessment |
|
| Xerophthalmia | Eye disorders | MedDRA 18.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Abdominal rigidity | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Aerophagia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Anal inflammation | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Duodenal ulcer | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Faecal incontinence | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Gastrointestinal angiodysplasia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Lip dry | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Odynophagia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Oral discomfort | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Oral mucosal eruption | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Reflux gastritis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Injection site inflammation | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Localised oedema | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Ulcer | General disorders | MedDRA 18.0 | Systematic Assessment |
|
| Cholestasis | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hepatocellular injury | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Bursitis infective staphylococcal | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Escherichia urinary tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Fungal infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Gastrointestinal fungal infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Genital herpes | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Genital infection fungal | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Herpes virus infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Nail infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Pleural infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Superinfection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Tinea pedis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Urinary tract infection staphylococcal | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Vulvitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
|
| Burn oesophageal | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
|
| Face crushing | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
|
| Scratch | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Aortic bruit | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Blood iron decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Blood phosphorus decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Ejection fraction decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Epidermal growth factor receptor decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Glomerular filtration rate decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Heart rate increased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Feeding disorder | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypoproteinaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypouricaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Metastatic pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
|
| Pyogenic granuloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
|
| Ageusia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Aphonia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Burning sensation | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dysaesthesia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hyperaesthesia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Motor dysfunction | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Myoclonus | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
|
| Anuria | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Leukocyturia | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
|
| Breast pain | Reproductive system and breast disorders | MedDRA 18.0 | Systematic Assessment |
|
| Genital paraesthesia | Reproductive system and breast disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA 18.0 | Systematic Assessment |
|
| Penile erythema | Reproductive system and breast disorders | MedDRA 18.0 | Systematic Assessment |
|
| Penile oedema | Reproductive system and breast disorders | MedDRA 18.0 | Systematic Assessment |
|
| Vaginal inflammation | Reproductive system and breast disorders | MedDRA 18.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hair growth abnormal | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Mucocutaneous rash | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Nail bed bleeding | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Onycholysis | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Prurigo | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Purpura | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Scab | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Skin oedema | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Skin reaction | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Skin toxicity | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Skin warm | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Toxic skin eruption | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Xeroderma | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
|
| Arterial thrombosis | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypertensive crisis | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Lymphoedema | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Thrombophlebitis superficial | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Venous thrombosis | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
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.
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 5 |
|
| Partial response |
|
| Stable disease/ Non-CR/Non-PD |
|
| Progressive disease (PD) |
|
| Not evaluable |
|
| Missing |
|
| Yes |
|
| Missing |
|
| Yes |
|
| Missing |
|
| 12 Weeks |
|
| 24 Weeks |
|
| Not applicable |
|
p-value for ratio outside interval 80% to 125%
| ANOVA | ANOVA (analysis of variance) model on the logarithm scale was used with 'subject' as random, whereas the 'treatment' as fixed effect. | 0.0149 | Ratio of adjusted gmeans in percentage | 95.36 | Standard Deviation | 15.4 | 2-Sided | 90 | 84.139 | 108.077 | Relative bioavailability of Afatinib with Docetaxel vs. Afatinib without Docetaxel was estimated by the ratios of the adjusted geometric means (gMean). Standard deviation is actually intra-individual geometric coefficient variation (gCV). | Yes | Non-Inferiority or Equivalence | p-value for ratio outside interval 80% to 125% |
| ANOVA | ANOVA (analysis of variance) model on the logarithm scale was used with 'subject' as random, whereas the 'treatment' as fixed effect. | 0.0208 | Ratio of adjusted gmeans in percentage | 88.12 | Standard Deviation | 9.2 | 2-Sided | 90 | 81.778 | 94.964 | Relative bioavailability of Afatinib with Docetaxel vs. Afatinib without Docetaxel was estimated by the ratios of the adjusted geometric means (gMean). Standard deviation is actually intra-individual geometric coefficient variation (gCV). | Yes | Non-Inferiority or Equivalence | p-value for ratio outside interval 80% to 125% |
p-value for ratio outside interval 80% to 125%
| ANOVA | ANOVA (analysis of variance) model on the logarithm scale was used with 'subject' as random, whereas the 'treatment' as fixed effect. | 0.6805 | Ratio of adjusted gmeans in percentage | 77.42 | Standard Deviation | 16.8 | 2-Sided | 90 | 68.516 | 87.473 | Relative bioavailability of Afatinib with Docetaxel vs. Afatinib without Docetaxel was estimated by the ratios of the adjusted geometric means (gMean). Standard deviation is actually intra-individual geometric coefficient variation (gCV). | Yes | Non-Inferiority or Equivalence | p-value for ratio outside interval 80% to 125% |
| ANOVA | ANOVA (analysis of variance) model on the logarithm scale was used with 'subject' as random, whereas the 'treatment' as fixed effect. | 0.2327 | Ratio of adjusted gmeans in percentage | 83.95 | Standard Deviation | 14.3 | 2-Sided | 90 | 74.794 | 94.217 | Relative bioavailability of Afatinib with Docetaxel vs. Afatinib without Docetaxel was estimated by the ratios of the adjusted geometric means (gMean). Standard deviation is actually intra-individual geometric coefficient variation (gCV). | Yes | Non-Inferiority or Equivalence | p-value for ratio outside interval 80% to 125% |
p-value for ratio outside interval 80% to 125%
p-value for ratio outside interval 80% to 125%
p-value for ratio outside interval 80% to 125%
| ANOVA | ANOVA (analysis of variance) model on the logarithm scale was used with 'subject' as random, whereas the 'treatment' as fixed effect. | 0.0405 | Ratio of adjusted gmeans in percentage | 98.11 | Standard Deviation | 30.4 | 2-Sided | 90 | 81.053 | 118.760 | Relative bioavailability of Docetaxel with Afatinib vs. Docetaxel without Afatinib was estimated by the ratios of the adjusted geometric means (gMean). Standard deviation is actually intra-individual geometric coefficient variation (gCV). | Yes | Non-Inferiority or Equivalence | p-value for ratio outside interval 80% to 125% |
p-value for ratio outside interval 80% to 125%
| ANOVA | ANOVA (analysis of variance) model on the logarithm scale was used with 'subject' as random, whereas the 'treatment' as fixed effect. | 0.3294 | Ratio of adjusted gmeans in percentage | 85.74 | Standard Deviation | 48.9 | 2-Sided | 90 | 65.561 | 112.138 | Relative bioavailability of Docetaxel with Afatinib vs. Docetaxel without Afatinib was estimated by the ratios of the adjusted geometric means (gMean). Standard deviation is actually intra-individual geometric coefficient variation (gCV). | Yes | Non-Inferiority or Equivalence | p-value for ratio outside interval 80% to 125% |