Neoplasms
Conditions
Brief summary
The primary objective of this trial is to identify the maximum tolerated dose (MTD) of BI 6727 therapy in terms of drug-related adverse events. Secondary objectives are the collection of overall safety and antitumour efficacy data and the determination of the pharmacokinetic profile of BI 6727.
Interventions
DRUGBI 6727
BI 6727
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumours, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment 2. Age 18 years or older 3. Written informed consent consistent with ICH-GCP and local legislation 4. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score ¿ 2 5. Recovery from CTCAE Grade 2 - 4 therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies (except alopecia) The 18 additional patients recruited at the MTD must also meet the following criterion: 6. Measurable tumour deposits (RECIST) by one or more techniques (CT, MRI)
Exclusion criteria
1. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol 2. Pregnancy or breastfeeding 3. Active infectious disease or known chronic Hepatitis B/Hepatitis C infection 4. Clinical evidence of active brain or leptomeningeal disease during the past 12 months 5. Second malignancy currently requiring active therapy 6. Absolute neutrophil count less than 1500 / mm3 7. Platelet count less than 100 000 / mm3 8. Bilirubin greater than 1.5 mg / dl (\> 26 ¿mol / L, SI unit equivalent) 9. Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal) 10. Serum creatinine greater than 1.5 mg / dl (\> 132 ¿mol / L, SI unit equivalent) 11. Known history of relevant QT-prolongation, e.g. long QT-syndrome 12. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception 13. Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug) 14. Chemo-, radio or immunotherapy within the past four weeks before start of therapy or concomitantly with this trial. This restriction does not apply to steroids and bisphosphonates. 15. Patients unable to comply with the protocol 16. Active alcohol or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 21 days (first treatment course). | MTD is defined as: the dose of BI 6727 which is one dose tier below that dose at which two or more out of a maximum of six patients experienced dose-limiting toxicity (DLT). At the maximum tolerated dose, no more than one patient out of six patients may experience DLT, i.e. MTD is defined as the highest dose studied for which the incidence of dose-limiting toxicity is no more than 17% (i.e. 1/6 patients) during the first course. DLT is defined as drug related common terminology criteria for adverse events (CTCAE) grade 3 or 4 non haematological toxicity (except emesis or diarrhoea responding to supportive treatment), or drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection, or CTCAE Grade 4 thrombocytopenia . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Relevant Abnormalities | From baseline to the last value on treatment, up to 814 days. | Number of participants with clinically relevant abnormalities, occurring in \>5% of the total number of participants, is reported. Clinically relevant post baseline values with Common Terminology Criteria for Adverse Events (CTCAE) grades: * CTCAE grade ≥4 for White blood cell count (WBC) , Neutrophils (NEUT), NEUABS Lymphocytes (LMPH) if baseline CTCAE grade is not 4 * CTCAE grade ≥3 for Haemoglobin (HGB), Platelets count (PLTCT), Alkaline phosphatase (ALKP), serum glutamic-oxaloacetic-transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total bilirubin (TBILI), if baseline CTCAE grade is ≥3 increases of one grade * CTCAE grade ≥2 for other parameters, if baseline CTCAE grade is ≥2 increases of at least one grade |
| Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | At baseline and at end of treatment (up to 814 days). | ECOG score: The scale of ECOG score is defined as a six point categorical scale as described ranging from 0 (asymptomatic) to 5 (death). ECOG score change from baseline to end of treatment is calculated, and defined as = ECOG score at end of treatment - ECOG score at baseline. Scale of ECOG score change: The ECOG score changes from baseline score are categorized on a three point categorical scale: Improved, unchanged, and deteriorated. Improvement or deterioration of performance status required a decrease or an increase from baseline, respectively, of at least one point on the ECOG scale. The number of patients per category (improved, unchanged, deteriorated unknown) is reported. |
| Electrocardiogram (ECG) - QTcF Change From Baseline | At baseline and 5 minutes before infusion end, 1 hour after end of infusion and at 4 and 12 hours after start of infusion, at course 1. | Electrocardiogram (ECG) - QTcF change from baseline. QTcF intervals form the ECGs were analysed for changes during and after intravenous infusion of BI 300 mg dose over 1 hours and over 2 hours. For baseline ECG, the combined baseline, defined as the mean of the 2 triplicates at the time-point closest to but prior to the start of the infusion of both treatment courses, i.e. a common baseline is used for both treatment courses, was used. Mean is adjusted mean. Abbreviations: QTcF: QT interval, corrected for heart rate according to Fridericia's formula (seconds) = measured QT / (cube root of preceding RR interval) QT: Interval from the beginning of the Q wave to the end of the T wave on an ECG (seconds). CfB: Change from baseline. |
| Vital Signs - Blood Pressure | At baseline. | Systolic blood pressure and diastolic blood pressure are reported. |
| Vital Signs - Pulse Rate | At baseline. | Pulse rate is reported. |
| Number of Participants With Unconfirmed Best Overall Response | Up to 814 days. | For solid tumours, evaluation of tumour response was assessed according to the Response Evaluation Criteria in Solid Tumours (RECIST) definition. The overall response of target and non-target lesions together with or without the appearance of new lesions as reported by the investigator was assessed on a four point categorical scale as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to the RECIST criteria. In order to best handle measurements that were non-evaluable (NEV) a modified version of the RECIST criteria was used. If a RECIST overall response was deemed NEV, it could be further classified into non-evaluable clinically progressive disease (NEVCPD ) or non-evaluable clinically non-progressive disease (NEVCNPD), depending on the subjective assessment of the investigator. |
| Number of Participants With Progression | Up to 814 days. | Number of participants with progression of disease. Progressive disease is defined according to the Response Evaluation Criteria in Solid Tumours (RECIST) as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter. |
| Maximum Concentration of BI 6727 in Plasma (Cmax) | At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727). | Maximum concentration of BI 6727 in plasma (Cmax). Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h: For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 4, 8, 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727). For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 3, 4 and 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727). |
| Time From Dosing to Maximum Concentration (Tmax) | At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727). | Time from dosing to maximum concentration (tmax). Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h: For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 4, 8, 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727). For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 3, 4 and 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727). |
| Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 and 504 hours after start of infusion. (*Immediately prior to end of infusion of BI 6727). | Area under the concentration-time curve of BI 6727 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). |
| Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 and 504 hours after start of infusion (*immediately prior to end of infusion of BI 6727). | Area under the concentration-time curve of BI 6727 in plasma over the time interval from 0 to the last quantifiable time point tz (AUC0-tz). Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h: For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 4, 8, 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727). For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 3, 4 and 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727). |
| Number of Participants With Adverse Events (AEs) | From first drug administration until last drug administration plus 21 days, up to 835 days. | Number of participants with adverse events. The events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.3.0. Grade refers to the severity of adverse event. Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE. |
| Terminal Half-life of the Analyte in Plasma (t1/2) | At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727). | Terminal half-life of the analyte in plasma (t1/2). |
| Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727). | Mean residence time of BI 6727 in the body after intravenous administration (MRT). |
| Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727). | Total clearance of BI 6727 in the plasma after intravascular adminstration (CL). |
| Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727). | Apparent volume of distribution at steady state following intravascular administration (Vss). |
| Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727). | Apparent volume of distribution during the terminal phase λz following an intravascular dose (Vz). |
| Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion. | Amount of BI 6727 that is eliminated in urine from the time point 0 to time point 24 hours (Ae0-24). |
| Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion. | Amount of BI 6727 that is eliminated in urine from the time point 0 to time point 48 hours (Ae0-48). |
| Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion. | Fraction of BI 6727 (percentage of dose) eliminated in urine from time point 0 to time point 24 hours (Fe0-24). |
| Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion. | Fraction of BI 6727 (percentage of dose) eliminated in urine from time point 0 to time point 48 hours (Fe0-48). |
| Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion. | Renal clearance of BI 6727 from the time point 0 to time point 24 hours (CLr,0-24). |
| Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | 5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion. | Renal clearance of BI 6727 from the time point 0 to time point 48 hours (CLr,0-48). |
| Terminal Rate Constant in Plasma (λz) | At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727). | Terminal rate constant in plasma (λz). |
Countries
Belgium
Participant flow
Recruitment details
An open label, uncontrolled first in man dose escalation trial in patients with advanced solid tumours with repeated administration in patients with clinical benefit.
Pre-assignment details
All patients were screened for eligibility to participate in the trial. Patients attended specialist sites to ensure that all patients met all inclusion/exclusion criteria. Patients were not to be entered to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| 12 mg BI 6727 12 milligram (mg) solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients). | 4 |
| 24 mg BI 6727 24 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients). | 3 |
| 48 mg BI 6727 48 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients). | 3 |
| 75 mg BI 6727 75 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients). | 2 |
| 125 mg BI 6727 125 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients). | 4 |
| 200 mg BI 6727 200 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients). | 3 |
| 300 mg BI 6727 300 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients). | 15 |
| 300 mg BI 6727 1h2h 300 mg solution for injection of BI 6727 was administered as intravenous infusion over 1 hour (1h) in course 1 and over 2 hours (2h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort. | 8 |
| 300 mg BI 6727 2h1h 300 mg solution for injection of BI 6727 was administered as intravenous infusion over 2 hour (2h) in course 1 and over 1 hour (1h) in course 2 once every 21 days (as long as there was clinical benefit for the patients). QT extension cohort. | 6 |
| 350 mg BI 6727 350 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients). | 5 |
| 400 mg BI 6727 400 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients). | 10 |
| 450 mg BI 6727 450 mg solution for injection of BI 6727 was administered as intravenous infusion over 60 minutes once every 21 days (as long as there was clinical benefit for the patients). | 2 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Adverse Event study disease worse | 4 | 3 | 3 | 2 | 4 | 3 | 14 | 6 | 6 | 5 | 10 | 1 |
| Overall Study | Sponsor decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 12 mg BI 6727 | Total | 450 mg BI 6727 | 400 mg BI 6727 | 350 mg BI 6727 | 300 mg BI 6727 2h1h | 300 mg BI 6727 1h2h | 300 mg BI 6727 | 200 mg BI 6727 | 125 mg BI 6727 | 75 mg BI 6727 | 48 mg BI 6727 | 24 mg BI 6727 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.5 Years | 58.0 Years | 50.0 Years | 60.0 Years | 61.0 Years | 60.5 Years | 54.5 Years | 55.0 Years | 65.0 Years | 58.5 Years | 57.0 Years | 43.0 Years | 53.0 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 65 Participants | 2 Participants | 10 Participants | 5 Participants | 6 Participants | 8 Participants | 15 Participants | 3 Participants | 4 Participants | 2 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 3 Participants | 27 Participants | 0 Participants | 5 Participants | 3 Participants | 2 Participants | 1 Participants | 6 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 38 Participants | 2 Participants | 5 Participants | 2 Participants | 4 Participants | 7 Participants | 9 Participants | 2 Participants | 3 Participants | 0 Participants | 3 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 2 / 3 | 1 / 3 | 1 / 2 | 1 / 4 | 1 / 3 | 6 / 15 | 4 / 8 | 2 / 6 | 0 / 5 | 2 / 10 | 0 / 2 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 2 / 3 | 1 / 2 | 4 / 4 | 3 / 3 | 15 / 15 | 8 / 8 | 6 / 6 | 3 / 5 | 10 / 10 | 2 / 2 |
| serious Total, serious adverse events | 3 / 4 | 2 / 3 | 2 / 3 | 1 / 2 | 0 / 4 | 2 / 3 | 9 / 15 | 3 / 8 | 1 / 6 | 3 / 5 | 5 / 10 | 2 / 2 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
MTD is defined as: the dose of BI 6727 which is one dose tier below that dose at which two or more out of a maximum of six patients experienced dose-limiting toxicity (DLT). At the maximum tolerated dose, no more than one patient out of six patients may experience DLT, i.e. MTD is defined as the highest dose studied for which the incidence of dose-limiting toxicity is no more than 17% (i.e. 1/6 patients) during the first course. DLT is defined as drug related common terminology criteria for adverse events (CTCAE) grade 3 or 4 non haematological toxicity (except emesis or diarrhoea responding to supportive treatment), or drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection, or CTCAE Grade 4 thrombocytopenia .
Time frame: 21 days (first treatment course).
Population: Treated Set (TS): All patients who received at least one dose of BI 6727.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 6727 | Maximum Tolerated Dose (MTD) | 400 Milligram (mg) |
Secondary
Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24)
Amount of BI 6727 that is eliminated in urine from the time point 0 to time point 24 hours (Ae0-24).
Time frame: 5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.
Population: Only patients in the treated set (TS) who had non-missing values were included in the analysis. Descriptive statistics for the 200 mg group could not be evaluated, since plasma concentrations of BI 6727 was only quantifiable in less than two-thirds of the patients. Descriptive statistics is calculated in case that 2/3 patients of total could be evaluated, as defined in the trial statistical analysis plan (TSAP).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 299 Microgram (µg) | Geometric Coefficient of Variation 12.4 |
| 24 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 493 Microgram (µg) | Geometric Coefficient of Variation 104 |
| 48 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 1580 Microgram (µg) | Geometric Coefficient of Variation 12.9 |
| 75 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 1170 Microgram (µg) | Geometric Coefficient of Variation 72.9 |
| 125 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 2120 Microgram (µg) | Geometric Coefficient of Variation 14.8 |
| 200 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | NA Microgram (µg) | — |
| 300 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 5960 Microgram (µg) | Geometric Coefficient of Variation 56.5 |
| 300 mg BI 6727 1h2h | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 3280 Microgram (µg) | Geometric Coefficient of Variation 64.1 |
| 300 mg BI 6727 2h1h | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 3800 Microgram (µg) | Geometric Coefficient of Variation 82.2 |
| 350 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 9790 Microgram (µg) | Geometric Coefficient of Variation 84.8 |
| 400 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 4820 Microgram (µg) | Geometric Coefficient of Variation 58.5 |
| 450 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) | 6010 Microgram (µg) | Geometric Coefficient of Variation 26.7 |
Secondary
Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48)
Amount of BI 6727 that is eliminated in urine from the time point 0 to time point 48 hours (Ae0-48).
Time frame: 5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.
Population: Only patients in the treated set (TS) who had non-missing values were included in the analysis. Descriptive statistics for 200mg and 350mg group could not be evaluated, since plasma concentrations of BI 6727 was only quantifiable in less than two-thirds of the patients, respectively. Descriptive statistics is calculated in case that 2/3 patients of total could be evaluated, as defined in the trial statistical analysis plan (TSAP).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 379 Microgram (µg) | Geometric Coefficient of Variation 26.1 |
| 24 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 618 Microgram (µg) | Geometric Coefficient of Variation 105 |
| 48 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 2030 Microgram (µg) | Geometric Coefficient of Variation 15.7 |
| 75 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 1380 Microgram (µg) | Geometric Coefficient of Variation 66.5 |
| 125 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 2630 Microgram (µg) | Geometric Coefficient of Variation 14.6 |
| 200 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | NA Microgram (µg) | — |
| 300 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 7810 Microgram (µg) | Geometric Coefficient of Variation 58.8 |
| 300 mg BI 6727 1h2h | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 4830 Microgram (µg) | Geometric Coefficient of Variation 76.7 |
| 300 mg BI 6727 2h1h | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 5810 Microgram (µg) | Geometric Coefficient of Variation 81.6 |
| 350 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | NA Microgram (µg) | — |
| 400 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 6650 Microgram (µg) | Geometric Coefficient of Variation 57.4 |
| 450 mg BI 6727 | Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) | 7930 Microgram (µg) | Geometric Coefficient of Variation 26.2 |
Secondary
Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss)
Apparent volume of distribution at steady state following intravascular administration (Vss).
Time frame: At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).
Population: Only patients in the treated set who had non-missing values were included in the analysis. For arms with 0 patients analysed: No sufficient data had been collected to determine the terminal half-life T1/2, which is needed to analyse the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | 7730 Liter | Geometric Coefficient of Variation 30.8 |
| 24 mg BI 6727 | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | 6670 Liter | Geometric Coefficient of Variation 46 |
| 48 mg BI 6727 | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | 9630 Liter | Geometric Coefficient of Variation 36.7 |
| 75 mg BI 6727 | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | 7520 Liter | Geometric Coefficient of Variation 50.9 |
| 125 mg BI 6727 | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | 9320 Liter | Geometric Coefficient of Variation 13.3 |
| 200 mg BI 6727 | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | 4580 Liter | Geometric Coefficient of Variation 41.2 |
| 300 mg BI 6727 | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | 4450 Liter | Geometric Coefficient of Variation 37.1 |
| 350 mg BI 6727 | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | 4570 Liter | Geometric Coefficient of Variation 19.8 |
| 400 mg BI 6727 | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | 4380 Liter | Geometric Coefficient of Variation 49.3 |
| 450 mg BI 6727 | Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) | 3640 Liter | Geometric Coefficient of Variation 20.1 |
Secondary
Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz)
Apparent volume of distribution during the terminal phase λz following an intravascular dose (Vz).
Time frame: At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).
Population: Only patients in the treated set who had non-missing values were included in the analysis. For arms with 0 patients analysed: No sufficient data had been collected to determine the terminal half-life T1/2, which is needed to analyse the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | 9530 Liter (L) | Geometric Coefficient of Variation 34.8 |
| 24 mg BI 6727 | Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | 8100 Liter (L) | Geometric Coefficient of Variation 52.6 |
| 48 mg BI 6727 | Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | 12400 Liter (L) | Geometric Coefficient of Variation 46.2 |
| 75 mg BI 6727 | Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | 9980 Liter (L) | Geometric Coefficient of Variation 38.8 |
| 125 mg BI 6727 | Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | 12500 Liter (L) | Geometric Coefficient of Variation 15.1 |
| 200 mg BI 6727 | Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | 7070 Liter (L) | Geometric Coefficient of Variation 19.4 |
| 300 mg BI 6727 | Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | 6940 Liter (L) | Geometric Coefficient of Variation 38 |
| 350 mg BI 6727 | Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | 6010 Liter (L) | Geometric Coefficient of Variation 28.1 |
| 400 mg BI 6727 | Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | 6770 Liter (L) | Geometric Coefficient of Variation 54.7 |
| 450 mg BI 6727 | Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) | 6000 Liter (L) | Geometric Coefficient of Variation 35.1 |
Secondary
Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve of BI 6727 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf).
Time frame: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 and 504 hours after start of infusion. (*Immediately prior to end of infusion of BI 6727).
Population: Only patients in the treated set who had non-missing values were included in the analysis. For arms with 0 patients analysed: No sufficient data had been collected to determine the terminal half-life T1/2, which is needed to analyse the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 149 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 31.6 |
| 24 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 380 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 38.9 |
| 48 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 778 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 25.1 |
| 75 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 1270 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 7.64 |
| 125 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 2140 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 27.9 |
| 200 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 5670 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 36.7 |
| 300 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 6540 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 32.6 |
| 350 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 10000 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 57.6 |
| 400 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 7510 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 19.3 |
| 450 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 10900 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 14 |
Secondary
Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz)
Area under the concentration-time curve of BI 6727 in plasma over the time interval from 0 to the last quantifiable time point tz (AUC0-tz). Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h: For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 4, 8, 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727). For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 3, 4 and 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727).
Time frame: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 and 504 hours after start of infusion (*immediately prior to end of infusion of BI 6727).
Population: Treated Set (TS): All patients who received at least one dose of BI 6727. Only patients with non-missing values were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 101 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 39 |
| 24 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 320 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 52 |
| 48 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 636 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 25.8 |
| 75 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 1110 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 15.9 |
| 125 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 1800 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 20.6 |
| 200 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 4780 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 20 |
| 300 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 5680 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 26.4 |
| 300 mg BI 6727 1h2h | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 2420 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 52.3 |
| 300 mg BI 6727 2h1h | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 1730 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 53.7 |
| 350 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 8230 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 37.1 |
| 400 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 6990 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 18.5 |
| 450 mg BI 6727 | Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) | 10300 Nanogram * Hours / Milliliter (ng*h/mL) | Geometric Coefficient of Variation 15.7 |
Secondary
Electrocardiogram (ECG) - QTcF Change From Baseline
Electrocardiogram (ECG) - QTcF change from baseline. QTcF intervals form the ECGs were analysed for changes during and after intravenous infusion of BI 300 mg dose over 1 hours and over 2 hours. For baseline ECG, the combined baseline, defined as the mean of the 2 triplicates at the time-point closest to but prior to the start of the infusion of both treatment courses, i.e. a common baseline is used for both treatment courses, was used. Mean is adjusted mean. Abbreviations: QTcF: QT interval, corrected for heart rate according to Fridericia's formula (seconds) = measured QT / (cube root of preceding RR interval) QT: Interval from the beginning of the Q wave to the end of the T wave on an ECG (seconds). CfB: Change from baseline.
Time frame: At baseline and 5 minutes before infusion end, 1 hour after end of infusion and at 4 and 12 hours after start of infusion, at course 1.
Population: QT extension cohort: Patients treated with 300 mg BI6727 to investigate QTc changes, according to two different treatment schedules in course 1 and course 2, (300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h). Results are reported for 300 mg over 1 hour infusion vs. 300 mg over 2 hours infusion. Only participants with non-missing data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| BI 6727 | Electrocardiogram (ECG) - QTcF Change From Baseline | CfB to 5 minutes before infusion end | 17.79 Millisecond (ms) |
| BI 6727 | Electrocardiogram (ECG) - QTcF Change From Baseline | CfB to 1 hours after infusion end | 13.99 Millisecond (ms) |
| BI 6727 | Electrocardiogram (ECG) - QTcF Change From Baseline | CfB to 4 hours after infusion start | 10.65 Millisecond (ms) |
| BI 6727 | Electrocardiogram (ECG) - QTcF Change From Baseline | CfB to 24 hours after infusion start | 4.33 Millisecond (ms) |
| 24 mg BI 6727 | Electrocardiogram (ECG) - QTcF Change From Baseline | CfB to 24 hours after infusion start | -4.33 Millisecond (ms) |
| 24 mg BI 6727 | Electrocardiogram (ECG) - QTcF Change From Baseline | CfB to 5 minutes before infusion end | 13.23 Millisecond (ms) |
| 24 mg BI 6727 | Electrocardiogram (ECG) - QTcF Change From Baseline | CfB to 4 hours after infusion start | 7.08 Millisecond (ms) |
| 24 mg BI 6727 | Electrocardiogram (ECG) - QTcF Change From Baseline | CfB to 1 hours after infusion end | 6.84 Millisecond (ms) |
Comparison: Change from baseline to 5 minutes before infusion end. Linear mixed model with sequence, course, treatment (both infusion types i.e. 1 hour duration and 2 hour duration) and time as fixed effects and treatment\*time as interaction effect, as well as the continuous , fixed covariate of baseline value.90% CI: [-10.59, 1.48]
Comparison: Change from baseline to 1 hour after infusion end. Linear mixed model with sequence, course, treatment (both infusion types i.e. 1 hour duration and 2 hour duration) and time as fixed effects and treatment\*time as interaction effect, as well as the continuous , fixed covariate of baseline value.90% CI: [-13.18, -1.11]
Comparison: Change from baseline to 4 hours after infusion start. Linear mixed model with sequence, course, treatment (both infusion types i.e. 1 hour duration and 2 hour duration) and time as fixed effects and treatment\*time as interaction effect, as well as the continuous , fixed covariate of baseline value.90% CI: [-9.61, 2.46]
Comparison: Change from baseline to 24 hours after infusion start. Linear mixed model with sequence, course, treatment (both infusion types i.e. 1 hour duration and 2 hour duration) and time as fixed effects and treatment\*time as interaction effect, as well as the continuous , fixed covariate of baseline value.90% CI: [-14.7, -2.63]
Secondary
Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24)
Fraction of BI 6727 (percentage of dose) eliminated in urine from time point 0 to time point 24 hours (Fe0-24).
Time frame: 5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.
Population: Only patients in the treated set (TS) who had non-missing values were included in the analysis. Descriptive statistics for 200 mg group could not be evaluated, since plasma concentrations of BI 6727 was only quantifiable in less than two-thirds of the patients. Descriptive statistics is calculated in case that 2/3 patients of total could be evaluated, as defined in the trial statistical analysis plan (TSAP).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 3.10 Percentage of dose | Geometric Coefficient of Variation 12.1 |
| 24 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 2.38 Percentage of dose | Geometric Coefficient of Variation 101 |
| 48 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 3.65 Percentage of dose | Geometric Coefficient of Variation 12.8 |
| 75 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 1.67 Percentage of dose | Geometric Coefficient of Variation 70.8 |
| 125 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 1.74 Percentage of dose | Geometric Coefficient of Variation 13.1 |
| 200 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | NA Percentage of dose | — |
| 300 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 1.99 Percentage of dose | Geometric Coefficient of Variation 56 |
| 300 mg BI 6727 1h2h | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 1.09 Percentage of dose | Geometric Coefficient of Variation 64.1 |
| 300 mg BI 6727 2h1h | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 1.27 Percentage of dose | Geometric Coefficient of Variation 82.2 |
| 350 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 2.80 Percentage of dose | Geometric Coefficient of Variation 84.8 |
| 400 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 1.19 Percentage of dose | Geometric Coefficient of Variation 58.4 |
| 450 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) | 1.42 Percentage of dose | Geometric Coefficient of Variation 35.7 |
Secondary
Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48)
Fraction of BI 6727 (percentage of dose) eliminated in urine from time point 0 to time point 48 hours (Fe0-48).
Time frame: 5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.
Population: Only patients in the treated set (TS) who had non-missing values were included in the analysis. Descriptive statistics for 200mg and 350mg group could not be evaluated, since plasma concentrations of BI 6727 was only quantifiable in less than two-thirds of the patients, respectively. Descriptive statistics is calculated in case that 2/3 patients of total could be evaluated, as defined in the trial statistical analysis plan (TSAP).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 3.75 Percentage of dose | Geometric Coefficient of Variation 27 |
| 24 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 2.98 Percentage of dose | Geometric Coefficient of Variation 102 |
| 48 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 4.71 Percentage of dose | Geometric Coefficient of Variation 16.2 |
| 75 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 1.98 Percentage of dose | Geometric Coefficient of Variation 64.5 |
| 125 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 2.16 Percentage of dose | Geometric Coefficient of Variation 11.1 |
| 200 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | NA Percentage of dose | — |
| 300 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 2.61 Percentage of dose | Geometric Coefficient of Variation 58.3 |
| 300 mg BI 6727 1h2h | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 1.61 Percentage of dose | Geometric Coefficient of Variation 76.7 |
| 300 mg BI 6727 2h1h | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 1.94 Percentage of dose | Geometric Coefficient of Variation 81.6 |
| 350 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | NA Percentage of dose | — |
| 400 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 1.65 Percentage of dose | Geometric Coefficient of Variation 57.2 |
| 450 mg BI 6727 | Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) | 1.87 Percentage of dose | Geometric Coefficient of Variation 35.1 |
Secondary
Maximum Concentration of BI 6727 in Plasma (Cmax)
Maximum concentration of BI 6727 in plasma (Cmax). Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h: For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 4, 8, 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727). For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 3, 4 and 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727).
Time frame: At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).
Population: Treated Set (TS): All patients who received at least one dose of BI 6727. Only patients with non-missing values were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Maximum Concentration of BI 6727 in Plasma (Cmax) | 18.8 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 14.3 |
| 24 mg BI 6727 | Maximum Concentration of BI 6727 in Plasma (Cmax) | 50.7 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 12.4 |
| 48 mg BI 6727 | Maximum Concentration of BI 6727 in Plasma (Cmax) | 91.1 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 17.6 |
| 75 mg BI 6727 | Maximum Concentration of BI 6727 in Plasma (Cmax) | 169.0 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 11.7 |
| 125 mg BI 6727 | Maximum Concentration of BI 6727 in Plasma (Cmax) | 234.0 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 30.9 |
| 200 mg BI 6727 | Maximum Concentration of BI 6727 in Plasma (Cmax) | 470.0 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 57.6 |
| 300 mg BI 6727 | Maximum Concentration of BI 6727 in Plasma (Cmax) | 758 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 28.8 |
| 300 mg BI 6727 1h2h | Maximum Concentration of BI 6727 in Plasma (Cmax) | 519.0 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 60.3 |
| 300 mg BI 6727 2h1h | Maximum Concentration of BI 6727 in Plasma (Cmax) | 246.0 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 68.8 |
| 350 mg BI 6727 | Maximum Concentration of BI 6727 in Plasma (Cmax) | 724.0 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 23.6 |
| 400 mg BI 6727 | Maximum Concentration of BI 6727 in Plasma (Cmax) | 1020.0 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 20.9 |
| 450 mg BI 6727 | Maximum Concentration of BI 6727 in Plasma (Cmax) | 1450.0 Nanogram/ Milliliter (ng/mL) | Geometric Coefficient of Variation 8.81 |
Secondary
Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT)
Mean residence time of BI 6727 in the body after intravenous administration (MRT).
Time frame: At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).
Population: Only patients in the treated set who had non-missing values were included in the analysis. For arms with 0 patients analysed: No sufficient data had been collected to determine the terminal half-life T1/2, which is needed to analyse the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | 113 Hours (h) | Geometric Coefficient of Variation 33.6 |
| 24 mg BI 6727 | Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | 127 Hours (h) | Geometric Coefficient of Variation 11.3 |
| 48 mg BI 6727 | Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | 174 Hours (h) | Geometric Coefficient of Variation 36.2 |
| 75 mg BI 6727 | Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | 137 Hours (h) | Geometric Coefficient of Variation 40.4 |
| 125 mg BI 6727 | Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | 164 Hours (h) | Geometric Coefficient of Variation 29.6 |
| 200 mg BI 6727 | Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | 139 Hours (h) | Geometric Coefficient of Variation 74.1 |
| 300 mg BI 6727 | Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | 99.5 Hours (h) | Geometric Coefficient of Variation 38.7 |
| 350 mg BI 6727 | Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | 131 Hours (h) | Geometric Coefficient of Variation 62.4 |
| 400 mg BI 6727 | Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | 82.5 Hours (h) | Geometric Coefficient of Variation 43.5 |
| 450 mg BI 6727 | Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) | 88.1 Hours (h) | Geometric Coefficient of Variation 5.99 |
Secondary
Number of Participants With Adverse Events (AEs)
Number of participants with adverse events. The events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.3.0. Grade refers to the severity of adverse event. Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE.
Time frame: From first drug administration until last drug administration plus 21 days, up to 835 days.
Population: Treated Set (TS): All patients who received at least one dose of BI 6727.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 4 | 0 Participants |
| BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 5 | 2 Participants |
| BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 3 | 1 Participants |
| BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 2 | 0 Participants |
| BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 1 | 1 Participants |
| 24 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 2 | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 5 | 1 Participants |
| 24 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 1 | 1 Participants |
| 24 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 3 | 1 Participants |
| 24 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 4 | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 4 | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 1 | 1 Participants |
| 48 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 2 | 1 Participants |
| 48 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 3 | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 5 | 1 Participants |
| 75 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 4 | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 1 | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 5 | 1 Participants |
| 75 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 2 | 1 Participants |
| 75 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 3 | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 3 | 1 Participants |
| 125 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 1 | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 2 | 3 Participants |
| 125 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 5 | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 4 | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 2 | 2 Participants |
| 200 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 4 | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 1 | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 3 | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 5 | 1 Participants |
| 300 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 5 | 3 Participants |
| 300 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 2 | 6 Participants |
| 300 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 3 | 4 Participants |
| 300 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 1 | 2 Participants |
| 300 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 4 | 0 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Adverse Events (AEs) | Grade 4 | 1 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Adverse Events (AEs) | Grade 1 | 0 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Adverse Events (AEs) | Grade 2 | 2 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Adverse Events (AEs) | Grade 3 | 3 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Adverse Events (AEs) | Grade 5 | 2 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Adverse Events (AEs) | Grade 4 | 1 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Adverse Events (AEs) | Grade 3 | 2 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Adverse Events (AEs) | Grade 5 | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Adverse Events (AEs) | Grade 1 | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Adverse Events (AEs) | Grade 2 | 3 Participants |
| 350 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 4 | 1 Participants |
| 350 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 5 | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 2 | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 3 | 2 Participants |
| 350 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 1 | 1 Participants |
| 400 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 5 | 0 Participants |
| 400 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 1 | 1 Participants |
| 400 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 4 | 6 Participants |
| 400 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 2 | 1 Participants |
| 400 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 3 | 2 Participants |
| 450 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 3 | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 2 | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 4 | 2 Participants |
| 450 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 1 | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Adverse Events (AEs) | Grade 5 | 0 Participants |
Secondary
Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score
ECOG score: The scale of ECOG score is defined as a six point categorical scale as described ranging from 0 (asymptomatic) to 5 (death). ECOG score change from baseline to end of treatment is calculated, and defined as = ECOG score at end of treatment - ECOG score at baseline. Scale of ECOG score change: The ECOG score changes from baseline score are categorized on a three point categorical scale: Improved, unchanged, and deteriorated. Improvement or deterioration of performance status required a decrease or an increase from baseline, respectively, of at least one point on the ECOG scale. The number of patients per category (improved, unchanged, deteriorated unknown) is reported.
Time frame: At baseline and at end of treatment (up to 814 days).
Population: Treated Set (TS): All patients who received at least one dose of BI 6727.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 1 Participants |
| BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 1 Participants |
| BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 2 Participants |
| 24 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 1 Participants |
| 24 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 2 Participants |
| 48 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 1 Participants |
| 48 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 2 Participants |
| 48 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 1 Participants |
| 75 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 1 Participants |
| 125 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 3 Participants |
| 125 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 1 Participants |
| 125 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 2 Participants |
| 200 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 1 Participants |
| 200 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 300 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 7 Participants |
| 300 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 7 Participants |
| 300 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 300 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 1 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 1 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 2 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 5 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 2 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 4 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 2 Participants |
| 350 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 3 Participants |
| 400 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 0 Participants |
| 400 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 8 Participants |
| 400 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 2 Participants |
| 400 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Improved | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unchanged | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Deteriorated | 2 Participants |
| 450 mg BI 6727 | Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score | Unknown | 0 Participants |
Secondary
Number of Participants With Clinically Relevant Abnormalities
Number of participants with clinically relevant abnormalities, occurring in \>5% of the total number of participants, is reported. Clinically relevant post baseline values with Common Terminology Criteria for Adverse Events (CTCAE) grades: * CTCAE grade ≥4 for White blood cell count (WBC) , Neutrophils (NEUT), NEUABS Lymphocytes (LMPH) if baseline CTCAE grade is not 4 * CTCAE grade ≥3 for Haemoglobin (HGB), Platelets count (PLTCT), Alkaline phosphatase (ALKP), serum glutamic-oxaloacetic-transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total bilirubin (TBILI), if baseline CTCAE grade is ≥3 increases of one grade * CTCAE grade ≥2 for other parameters, if baseline CTCAE grade is ≥2 increases of at least one grade
Time frame: From baseline to the last value on treatment, up to 814 days.
Population: Treated Set (TS): All patients who received at least one dose of BI 6727.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 1 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 0 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Platelets | 0 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 0 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 0 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 0 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 0 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Sodium | 0 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Glucose | 1 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 1 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Albumin | 0 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 0 Participants |
| BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Albumin | 1 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Platelets | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Glucose | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 1 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 2 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Sodium | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 2 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Glucose | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 1 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 1 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 1 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Albumin | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 1 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Sodium | 1 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Platelets | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Sodium | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Albumin | 1 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 1 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 1 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Glucose | 1 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Platelets | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 1 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Platelets | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 2 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 2 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 2 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Glucose | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Sodium | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 1 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Albumin | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Sodium | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 1 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Glucose | 1 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 1 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 3 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Albumin | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 2 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 1 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Platelets | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 1 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 1 Participants |
| 200 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 0 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Glucose | 3 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 0 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 2 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 10 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 2 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 2 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Platelets | 2 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 7 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 1 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 2 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Sodium | 1 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Albumin | 5 Participants |
| 300 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 1 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Platelets | 0 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 1 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 1 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Albumin | 0 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 0 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 0 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 2 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 0 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 4 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Glucose | 2 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Sodium | 1 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 4 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 2 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 1 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 1 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Platelets | 2 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 1 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 1 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 2 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Sodium | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Albumin | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Glucose | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 1 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 1 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 1 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 1 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Albumin | 2 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Glucose | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 2 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 3 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Platelets | 1 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 2 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Sodium | 1 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 2 Participants |
| 350 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 4 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 6 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 2 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 7 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Sodium | 2 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 1 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Glucose | 2 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 1 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 3 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Albumin | 2 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 2 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 4 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 0 Participants |
| 400 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Platelets | 4 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Sodium | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Mean corpuscular volume (MCV) | 1 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | White blood cell count (WBC) | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haemoglobin | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Creatinine | 1 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Neutrophils | 2 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Haematocrit | 1 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Lactate dehydrogenase (LDH) | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Glucose | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Albumin | 1 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Alkaline phosphatase | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Red blood cell count (RBC) | 2 Participants |
| 450 mg BI 6727 | Number of Participants With Clinically Relevant Abnormalities | Platelets | 2 Participants |
Secondary
Number of Participants With Progression
Number of participants with progression of disease. Progressive disease is defined according to the Response Evaluation Criteria in Solid Tumours (RECIST) as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter.
Time frame: Up to 814 days.
Population: Treated Set (TS): All patients who received at least one dose of BI 6727.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 6727 | Number of Participants With Progression | 3 Participants |
| 24 mg BI 6727 | Number of Participants With Progression | 3 Participants |
| 48 mg BI 6727 | Number of Participants With Progression | 3 Participants |
| 75 mg BI 6727 | Number of Participants With Progression | 2 Participants |
| 125 mg BI 6727 | Number of Participants With Progression | 4 Participants |
| 200 mg BI 6727 | Number of Participants With Progression | 3 Participants |
| 300 mg BI 6727 | Number of Participants With Progression | 15 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Progression | 7 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Progression | 6 Participants |
| 350 mg BI 6727 | Number of Participants With Progression | 5 Participants |
| 400 mg BI 6727 | Number of Participants With Progression | 10 Participants |
| 450 mg BI 6727 | Number of Participants With Progression | 1 Participants |
Secondary
Number of Participants With Unconfirmed Best Overall Response
For solid tumours, evaluation of tumour response was assessed according to the Response Evaluation Criteria in Solid Tumours (RECIST) definition. The overall response of target and non-target lesions together with or without the appearance of new lesions as reported by the investigator was assessed on a four point categorical scale as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to the RECIST criteria. In order to best handle measurements that were non-evaluable (NEV) a modified version of the RECIST criteria was used. If a RECIST overall response was deemed NEV, it could be further classified into non-evaluable clinically progressive disease (NEVCPD ) or non-evaluable clinically non-progressive disease (NEVCNPD), depending on the subjective assessment of the investigator.
Time frame: Up to 814 days.
Population: Treated Set (TS): All patients who received at least one dose of BI 6727.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 1 Participants |
| BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 2 Participants |
| BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Unknown | 1 Participants |
| BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 0 Participants |
| BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 0 Participants |
| 24 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 2 Participants |
| 24 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 1 Participants |
| 24 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 1 Participants |
| 48 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 0 Participants |
| 48 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 2 Participants |
| 75 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 75 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 2 Participants |
| 75 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 2 Participants |
| 125 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 125 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 1 Participants |
| 125 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 1 Participants |
| 200 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 2 Participants |
| 200 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 1 Participants |
| 200 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 0 Participants |
| 200 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
| 300 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 300 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 0 Participants |
| 300 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 8 Participants |
| 300 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 0 Participants |
| 300 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 7 Participants |
| 300 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 3 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 4 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 1 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 0 Participants |
| 300 mg BI 6727 1h2h | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 4 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 0 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 2 Participants |
| 300 mg BI 6727 2h1h | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 1 Participants |
| 350 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 4 Participants |
| 350 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 350 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
| 400 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 400 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 5 Participants |
| 400 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 1 Participants |
| 400 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 1 Participants |
| 400 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
| 400 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 3 Participants |
| 450 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Stable disease | 1 Participants |
| 450 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Progressive Disease (PD) or NEVCPD | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Complete response | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Partial Response | 1 Participants |
| 450 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Non-evaluable, clinically non-progressive disease (NEVCNPD) | 0 Participants |
| 450 mg BI 6727 | Number of Participants With Unconfirmed Best Overall Response | Unknown | 0 Participants |
Secondary
Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24)
Renal clearance of BI 6727 from the time point 0 to time point 24 hours (CLr,0-24).
Time frame: 5 minutes prior to the infusion on day 1, course 1 and up to 24 hours after the infusion.
Population: Only patients in the treated set (TS) who had non-missing values were included in the analysis. Descriptive statistics for 200 mg group could not be evaluated, since plasma concentrations of BI 6727 was only quantifiable in less than two-thirds of the patients. Descriptive statistics is calculated in case that 2/3 patients of total could be evaluated, as defined in the trial statistical analysis plan (TSAP).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 106 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 11.5 |
| 24 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 87.6 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 67.8 |
| 48 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 127 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 11.8 |
| 75 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 48.4 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 117 |
| 125 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 56.7 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 11.4 |
| 200 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | NA Milliliter/minutes (mL/min) | — |
| 300 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 42.3 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 69.3 |
| 300 mg BI 6727 1h2h | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 34.5 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 54.9 |
| 300 mg BI 6727 2h1h | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 34.2 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 58.3 |
| 350 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 66.7 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 89.9 |
| 400 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 24.5 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 82.9 |
| 450 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) | 21.6 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 15.3 |
Secondary
Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48)
Renal clearance of BI 6727 from the time point 0 to time point 48 hours (CLr,0-48).
Time frame: 5 minutes prior to the infusion on day 1, course 1 and up to 48 hours after the infusion.
Population: Only patients in the treated set with non-missing values. For arms with 0 patients analysed: No sufficient data had been collected to determine the terminal half-life T1/2, which is needed to analyse the PK data. Descriptive statistics for 200 and 350 mg group could not be evaluated, since plasma concentrations of BI 6727 was only quantifiable in less than 2/3 of patients, respectively. Descriptive statistics is calculated in case that 2/3 patients of total could be evaluated as defined in TSAP.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | 99.8 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 5.89 |
| 24 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | 80.6 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 62.2 |
| 48 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | 118 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 13.5 |
| 75 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | 43.9 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 116 |
| 125 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | 51.6 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 3.77 |
| 200 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | NA Milliliter/minutes (mL/min) | — |
| 300 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | 41.3 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 71.8 |
| 350 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | NA Milliliter/minutes (mL/min) | — |
| 400 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | 25.8 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 80.9 |
| 450 mg BI 6727 | Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) | 21.5 Milliliter/minutes (mL/min) | Geometric Coefficient of Variation 14.6 |
Secondary
Terminal Half-life of the Analyte in Plasma (t1/2)
Terminal half-life of the analyte in plasma (t1/2).
Time frame: At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).
Population: Only patients in the treated set who had non-missing values were included in the analysis. For arms with 0 patients analysed: No sufficient data had been collected to determine the terminal half-life T1/2, which is needed to analyse the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Terminal Half-life of the Analyte in Plasma (t1/2) | 96.9 Hours (h) | Geometric Coefficient of Variation 32 |
| 24 mg BI 6727 | Terminal Half-life of the Analyte in Plasma (t1/2) | 107 Hours (h) | Geometric Coefficient of Variation 16.9 |
| 48 mg BI 6727 | Terminal Half-life of the Analyte in Plasma (t1/2) | 156 Hours (h) | Geometric Coefficient of Variation 40.1 |
| 75 mg BI 6727 | Terminal Half-life of the Analyte in Plasma (t1/2) | 126 Hours (h) | Geometric Coefficient of Variation 28.9 |
| 125 mg BI 6727 | Terminal Half-life of the Analyte in Plasma (t1/2) | 153 Hours (h) | Geometric Coefficient of Variation 30.7 |
| 200 mg BI 6727 | Terminal Half-life of the Analyte in Plasma (t1/2) | 149 Hours (h) | Geometric Coefficient of Variation 49.4 |
| 300 mg BI 6727 | Terminal Half-life of the Analyte in Plasma (t1/2) | 105 Hours (h) | Geometric Coefficient of Variation 27.2 |
| 350 mg BI 6727 | Terminal Half-life of the Analyte in Plasma (t1/2) | 119 Hours (h) | Geometric Coefficient of Variation 37.6 |
| 400 mg BI 6727 | Terminal Half-life of the Analyte in Plasma (t1/2) | 88.4 Hours (h) | Geometric Coefficient of Variation 49.2 |
| 450 mg BI 6727 | Terminal Half-life of the Analyte in Plasma (t1/2) | 101 Hours (h) | Geometric Coefficient of Variation 20.4 |
Secondary
Terminal Rate Constant in Plasma (λz)
Terminal rate constant in plasma (λz).
Time frame: At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).
Population: Only patients in the treated set who had non-missing values were included in the analysis. For arms with 0 patients analysed: No sufficient data had been collected to determine the terminal half-life T1/2, which is needed to analyse the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Terminal Rate Constant in Plasma (λz) | 0.00715 1 / hour | Geometric Coefficient of Variation 32 |
| 24 mg BI 6727 | Terminal Rate Constant in Plasma (λz) | 0.00649 1 / hour | Geometric Coefficient of Variation 16.9 |
| 48 mg BI 6727 | Terminal Rate Constant in Plasma (λz) | 0.00446 1 / hour | Geometric Coefficient of Variation 40.1 |
| 75 mg BI 6727 | Terminal Rate Constant in Plasma (λz) | 0.00552 1 / hour | Geometric Coefficient of Variation 28.9 |
| 125 mg BI 6727 | Terminal Rate Constant in Plasma (λz) | 0.00454 1 / hour | Geometric Coefficient of Variation 30.7 |
| 200 mg BI 6727 | Terminal Rate Constant in Plasma (λz) | 0.00464 1 / hour | Geometric Coefficient of Variation 49.4 |
| 300 mg BI 6727 | Terminal Rate Constant in Plasma (λz) | 0.00658 1 / hour | Geometric Coefficient of Variation 27.2 |
| 350 mg BI 6727 | Terminal Rate Constant in Plasma (λz) | 0.00582 1 / hour | Geometric Coefficient of Variation 37.6 |
| 400 mg BI 6727 | Terminal Rate Constant in Plasma (λz) | 0.00784 1 / hour | Geometric Coefficient of Variation 49.2 |
| 450 mg BI 6727 | Terminal Rate Constant in Plasma (λz) | 0.00688 1 / hour | Geometric Coefficient of Variation 20.4 |
Secondary
Time From Dosing to Maximum Concentration (Tmax)
Time from dosing to maximum concentration (tmax). Different time frame for dose groups 300 mg BI 6727 1h2h and 300 mg BI 6727 2h1h: For 300mg BI 6727 1h2h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 4, 8, 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727). For 300mg BI 6727 2h1h: At course 1: 0.083 hours before drug administration and at 1\*, 2, 3, 4 and 24 hours after start of infusion (\*immediately prior to end of infusion of BI 6727).
Time frame: At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).
Population: Treated Set (TS): All patients who received at least one dose of BI 6727. Only patients with non-missing values were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 6727 | Time From Dosing to Maximum Concentration (Tmax) | 0.667 Hours (h) |
| 24 mg BI 6727 | Time From Dosing to Maximum Concentration (Tmax) | 0.750 Hours (h) |
| 48 mg BI 6727 | Time From Dosing to Maximum Concentration (Tmax) | 0.500 Hours (h) |
| 75 mg BI 6727 | Time From Dosing to Maximum Concentration (Tmax) | 0.884 Hours (h) |
| 125 mg BI 6727 | Time From Dosing to Maximum Concentration (Tmax) | 0.533 Hours (h) |
| 200 mg BI 6727 | Time From Dosing to Maximum Concentration (Tmax) | 1.00 Hours (h) |
| 300 mg BI 6727 | Time From Dosing to Maximum Concentration (Tmax) | 0.750 Hours (h) |
| 300 mg BI 6727 1h2h | Time From Dosing to Maximum Concentration (Tmax) | 1.00 Hours (h) |
| 300 mg BI 6727 2h1h | Time From Dosing to Maximum Concentration (Tmax) | 2.00 Hours (h) |
| 350 mg BI 6727 | Time From Dosing to Maximum Concentration (Tmax) | 0.750 Hours (h) |
| 400 mg BI 6727 | Time From Dosing to Maximum Concentration (Tmax) | 0.750 Hours (h) |
| 450 mg BI 6727 | Time From Dosing to Maximum Concentration (Tmax) | 0.517 Hours (h) |
Secondary
Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL)
Total clearance of BI 6727 in the plasma after intravascular adminstration (CL).
Time frame: At course 1: 0.083 hours before drug administration and at 0.25, 0.5, 075, 1*, 1.5, 2, 4, 8, 24, 48, 96, 168, 336 hours after start of infusion (*immediately prior to end of infusion of BI 6727).
Population: Only patients in the treated set who had non-missing values were included in the analysis. For arms with 0 patients analysed: No sufficient data had been collected to determine the terminal half-life T1/2, which is needed to analyse the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 6727 | Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | 1140 Milliliter/Minute (mL/min) | Geometric Coefficient of Variation 32.2 |
| 24 mg BI 6727 | Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | 876 Milliliter/Minute (mL/min) | Geometric Coefficient of Variation 44.4 |
| 48 mg BI 6727 | Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | 924 Milliliter/Minute (mL/min) | Geometric Coefficient of Variation 20.2 |
| 75 mg BI 6727 | Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | 918 Milliliter/Minute (mL/min) | Geometric Coefficient of Variation 9.17 |
| 125 mg BI 6727 | Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | 947 Milliliter/Minute (mL/min) | Geometric Coefficient of Variation 23.4 |
| 200 mg BI 6727 | Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | 547 Milliliter/Minute (mL/min) | Geometric Coefficient of Variation 28.8 |
| 300 mg BI 6727 | Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | 762 Milliliter/Minute (mL/min) | Geometric Coefficient of Variation 32.6 |
| 350 mg BI 6727 | Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | 583 Milliliter/Minute (mL/min) | Geometric Coefficient of Variation 57.6 |
| 400 mg BI 6727 | Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | 885 Milliliter/Minute (mL/min) | Geometric Coefficient of Variation 19.4 |
| 450 mg BI 6727 | Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) | 689 Milliliter/Minute (mL/min) | Geometric Coefficient of Variation 14 |
Secondary
Vital Signs - Blood Pressure
Systolic blood pressure and diastolic blood pressure are reported.
Time frame: At baseline.
Population: Treated Set (TS): All patients who received at least one dose of BI 6727.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BI 6727 | Vital Signs - Blood Pressure | Systolic blood pressure | 126 Millimeter of mercury (mmHg) |
| BI 6727 | Vital Signs - Blood Pressure | Diastolic blood pressure | 74 Millimeter of mercury (mmHg) |
| 24 mg BI 6727 | Vital Signs - Blood Pressure | Systolic blood pressure | 124 Millimeter of mercury (mmHg) |
| 24 mg BI 6727 | Vital Signs - Blood Pressure | Diastolic blood pressure | 80 Millimeter of mercury (mmHg) |
| 48 mg BI 6727 | Vital Signs - Blood Pressure | Systolic blood pressure | 124 Millimeter of mercury (mmHg) |
| 48 mg BI 6727 | Vital Signs - Blood Pressure | Diastolic blood pressure | 78 Millimeter of mercury (mmHg) |
| 75 mg BI 6727 | Vital Signs - Blood Pressure | Systolic blood pressure | 112 Millimeter of mercury (mmHg) |
| 75 mg BI 6727 | Vital Signs - Blood Pressure | Diastolic blood pressure | 75 Millimeter of mercury (mmHg) |
| 125 mg BI 6727 | Vital Signs - Blood Pressure | Diastolic blood pressure | 71.5 Millimeter of mercury (mmHg) |
| 125 mg BI 6727 | Vital Signs - Blood Pressure | Systolic blood pressure | 110 Millimeter of mercury (mmHg) |
| 200 mg BI 6727 | Vital Signs - Blood Pressure | Systolic blood pressure | 130 Millimeter of mercury (mmHg) |
| 200 mg BI 6727 | Vital Signs - Blood Pressure | Diastolic blood pressure | 76 Millimeter of mercury (mmHg) |
| 300 mg BI 6727 | Vital Signs - Blood Pressure | Diastolic blood pressure | 80 Millimeter of mercury (mmHg) |
| 300 mg BI 6727 | Vital Signs - Blood Pressure | Systolic blood pressure | 125 Millimeter of mercury (mmHg) |
| 300 mg BI 6727 1h2h | Vital Signs - Blood Pressure | Systolic blood pressure | 129 Millimeter of mercury (mmHg) |
| 300 mg BI 6727 1h2h | Vital Signs - Blood Pressure | Diastolic blood pressure | 78.5 Millimeter of mercury (mmHg) |
| 300 mg BI 6727 2h1h | Vital Signs - Blood Pressure | Systolic blood pressure | 148 Millimeter of mercury (mmHg) |
| 300 mg BI 6727 2h1h | Vital Signs - Blood Pressure | Diastolic blood pressure | 86.5 Millimeter of mercury (mmHg) |
| 350 mg BI 6727 | Vital Signs - Blood Pressure | Systolic blood pressure | 135 Millimeter of mercury (mmHg) |
| 350 mg BI 6727 | Vital Signs - Blood Pressure | Diastolic blood pressure | 82 Millimeter of mercury (mmHg) |
| 400 mg BI 6727 | Vital Signs - Blood Pressure | Diastolic blood pressure | 81.5 Millimeter of mercury (mmHg) |
| 400 mg BI 6727 | Vital Signs - Blood Pressure | Systolic blood pressure | 144 Millimeter of mercury (mmHg) |
| 450 mg BI 6727 | Vital Signs - Blood Pressure | Diastolic blood pressure | 75 Millimeter of mercury (mmHg) |
| 450 mg BI 6727 | Vital Signs - Blood Pressure | Systolic blood pressure | 129 Millimeter of mercury (mmHg) |
Secondary
Vital Signs - Pulse Rate
Pulse rate is reported.
Time frame: At baseline.
Population: Treated Set (TS): All patients who received at least one dose of BI 6727.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 6727 | Vital Signs - Pulse Rate | 88 Beats per minute (bpm) |
| 24 mg BI 6727 | Vital Signs - Pulse Rate | 80 Beats per minute (bpm) |
| 48 mg BI 6727 | Vital Signs - Pulse Rate | 88 Beats per minute (bpm) |
| 75 mg BI 6727 | Vital Signs - Pulse Rate | 92 Beats per minute (bpm) |
| 125 mg BI 6727 | Vital Signs - Pulse Rate | 91 Beats per minute (bpm) |
| 200 mg BI 6727 | Vital Signs - Pulse Rate | 88 Beats per minute (bpm) |
| 300 mg BI 6727 | Vital Signs - Pulse Rate | 78 Beats per minute (bpm) |
| 300 mg BI 6727 1h2h | Vital Signs - Pulse Rate | 84 Beats per minute (bpm) |
| 300 mg BI 6727 2h1h | Vital Signs - Pulse Rate | 75 Beats per minute (bpm) |
| 350 mg BI 6727 | Vital Signs - Pulse Rate | 76 Beats per minute (bpm) |
| 400 mg BI 6727 | Vital Signs - Pulse Rate | 82 Beats per minute (bpm) |
| 450 mg BI 6727 | Vital Signs - Pulse Rate | 76 Beats per minute (bpm) |