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The primary objectives are to assess the safety and tolerability of single and repeated doses of EMD525797, and characterize Pharmacokinetics (PK). The secondary objectives are to investigate the immunogenicity and Progressive disease (PD), and to assess the anti-tumor activity of EMD525797.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EMD525797 250 milligram (mg) | Experimental |
| |
| EMD525797 500 mg | Experimental |
| |
| EMD525797 1000 mg | Experimental |
| |
| EMD525797 1500 mg | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EMD525797 | Biological | Subjects will receive 250 milligram (mg) of EMD525797 intravenously every 2 weeks, until progressive disease (PD), unacceptable toxicity or withdrawal of consent. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Dose-limiting Toxicities (DLTs) | DLT was defined as any Grade 3 or 4 haematological or non-haematological toxicity occurring at any dose level until the end of Week 4, and suspected to be reasonably related to the investigational medicinal product by the Investigator and/or Sponsor. Toxicities not considered to be DLTs are as follows- Allergic reactions or anaphylaxis; any Grade 3 or 4 out-of-range laboratory values without any clinical correlate, which were reversible within 7 days, unless the Investigator decided this event is clinically significant. For this reason Grade 3 or 4 out-of-range laboratory values must be re-assessed within 7 days. In case the Investigator provides the subject any treatment(s) due to the out-of-range laboratory values, the event was regarded as a DLT. | Baseline up to Week 4 |
| Maximum Observed Serum Concentration (Cmax): After Single Dose | Pre-dose, hour 1(end of infusion [EOI]), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 | |
| Maximum Observed Serum Concentration (Cmax) of EMD 525797:After Multiple Dose | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 | |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Single Dose | Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above Lower limit of quantification (LLQ). | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Multiple Dose | Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above LLQ. | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Overall Tumor Response | Overall tumor response was defined as the presence of at least one confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0. Complete response was defined as the disappearance of all target and non-target lesions and normalization of serum levels of tumor markers. PR is at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. |
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Inclusion Criteria:
Other protocol defined inclusion criteria could also apply
Exclusion Criteria:
Other protocol defined exclusion criteria could also apply
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Serono Co., Ltd., Japan | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For Recruiting | Locations in | Japan |
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| ID | Title | Description |
|---|---|---|
| FG000 | EMD525797 250 mg | 250 milligram (mg) of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| FG001 | EMD525797 500 mg | 500 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| FG002 | EMD525797 1000 mg | 1000 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| FG003 | EMD525797 1500 mg | 1500 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The all-subjects set included all the subjects who signed the informed consent and were treated.
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| ID | Title | Description |
|---|---|---|
| BG000 | EMD525797 250 mg | 250 milligram (mg) of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| BG001 | EMD525797 500 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects With Dose-limiting Toxicities (DLTs) | DLT was defined as any Grade 3 or 4 haematological or non-haematological toxicity occurring at any dose level until the end of Week 4, and suspected to be reasonably related to the investigational medicinal product by the Investigator and/or Sponsor. Toxicities not considered to be DLTs are as follows- Allergic reactions or anaphylaxis; any Grade 3 or 4 out-of-range laboratory values without any clinical correlate, which were reversible within 7 days, unless the Investigator decided this event is clinically significant. For this reason Grade 3 or 4 out-of-range laboratory values must be re-assessed within 7 days. In case the Investigator provides the subject any treatment(s) due to the out-of-range laboratory values, the event was regarded as a DLT. | Dose escalation analysis set/DLT analysis set included all subjects who experienced a DLT or subjects who did not experience a DLT and had a relative dose intensity of >= 75 percent (%) during the DLT observation period. | Posted | Number | subjects | Baseline up to Week 4 |
|
First dose of the study drug up to 31+/-3 days after the last administration of EMD 525797, assessed upto maximum of 22 months.
The safety analysis set included all subjects who received at least one (non-zero) administration of the trial medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | EMD525797 250 mg | 250 milligram (mg) of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colitis | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia Of Malignant Disease | Blood and lymphatic system disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Serono, a division of Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
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| EMD525797 | Biological | Subjects will receive 500 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity or withdrawal of consent. |
|
| EMD525797 | Biological | Subjects will receive 1000 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity or withdrawal of consent. |
|
| EMD525797 | Biological | Subjects will receive 1500 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity, or withdrawal of consent. |
|
| Total Body Clearance (CL) of EMD 525797: After Single Dose | Total body clearance of drug in serum was calculated: as CL= Dose divided by Area under the serum concentration-time curve from time zero to infinity (AUC0-inf). | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
| Total Body Clearance at Steady State (CLss) of EMD 525797 | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL of drug in serum was calculated as : CL= Dose/ AUC0-inf. Area under the serum concentration-time curve from time zero to infinity (AUC0-inf), calculated as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant. | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Apparent Volume of Distribution (Vz): After Single Dose | Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by elimination rate constant [λz]) following single dose. Area under the serum concentration-time curve from time zero to infinity, calculated (AUC0-inf) as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant. And the elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data. A minimum of three points is required to calculate λz. | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
| Pharmacokinetics of EMD 525797 - Trough Values | The observed serum concentration immediately before next dosing determined directly from the serum concentration-time profile of each subject (= trough concentration). | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Apparent Volume of Distribution: After Multiple Dose | Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/(Area under the serum concentration-time curve within one complete dosing interval [AUCtau]* λz) following multiple dose. | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Baseline up to Week 36 |
| Number of Subjects With Clinical Benefit | Clinical benefit was defined as presence of at least one confirmed CR, PR, or stable disease (SD) lasting at least 12 weeks according to RECIST v1.0. Per RECIST v1.0: CR was defined as disappearance of all target and non-target lesions and normalization of serum levels of tumor markers . PR was defined as >=30% decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non-target lesions. | Baseline up to Week 36 |
| Progression-free Survival (PFS) | PFS time was defined as the time (in months) from the first dosing date to the date of first documentation of disease progression as reported and documented by the Investigator (i.e. radiological progression per RECIST version 1.0) or death for any cause within 12 weeks after last tumor assessment. Subjects without event are censored on the date of last tumor assessment. | From first dosing date until disease progression or death, maximum up to Week 36 |
| Apparent Terminal Half Life (t1/2): After Single Dose | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
| Apparent Terminal Half Life (t1/2): After Multiple Dose | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Time to Maximum Observed Serum Concentration (Tmax): After Single Dose | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
| Time to Maximum Observed Serum Concentration (Tmax): After Multiple Dose | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Elimination Rate Constant (λz): After Single Dose | The elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data. | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
| Elimination Rate Constant ( λ z): After Multiple Dose | The elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data. | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Minimum Observed Serum Concentration (Cmin) After Multiple Doses | The observed minimum serum concentration determined directly from the serum concentration-time profile of each subject. | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Observed Serum Concentration Immediately Before Next Dosing (Cpre) | The observed serum concentration immediately before next dosing determined directly from the serum concentration-time profile of each subject (= trough concentration) | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Average Serum Concentration at Steady State (Cav) | The Cav was calculated by dividing the area under the serum concentration-time curve within one complete dosing interval (AUCtau) by the dosing interval (2 weeks or 336 hoursi.e. Cav =AUCtau/tau). | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Single Dose | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
| Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Multiple Dose | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Volume of Distribution at Steady State (Vss) | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) was the apparent volume of distribution at steady-state. | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Mean Residency Time (MRT0-inf) | MRT0-inf of drug in the body was calculated by dividing the area under the first moment curve from time zero to infinity with area under the first moment curve from time zero to infinity minus half of infusion of duration (MRT0-inf = AUMC0-inf/AUMC0-inf - T/2). | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
| Mean Residence Time at Steady State (MRTss) | MRTss = (AUMCtau + tau(AUCinf - AUCtau))/ AUCtau) - T/2, where AUMCtau was the area under the first moment curve within one complete dosing interval and T was the infusion duration. Area under the serum concentration-time curve from time zero to infinity, calculated as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant. | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Percentage Peak-Trough Fluctuation (PTF) | The peak trough fluctuation over one dosing interval at steady state, calculated as PTF (%) = ( [Cmax - Cmin] / Cav ) multiplied by 100. | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
| Accumulation Ratio (Rac) | Accumulation ratio for AUC, calculated as area under the serum concentration-time curve within one complete dosing interval at 3rd infusion divided by area under the serum concentration-time curve within one complete dosing interval at 1st infusion. | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 and Week 5 |
500 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent.
| BG002 | EMD525797 1000 mg | 1000 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| BG003 | EMD525797 1500 mg | 1500 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 | EMD525797 250 mg | 250 milligram (mg) of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| OG001 | EMD525797 500 mg | 500 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| OG002 | EMD525797 1000 mg | 1000 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| OG003 | EMD525797 1500 mg | 1500 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
|
|
| Primary | Maximum Observed Serum Concentration (Cmax): After Single Dose | The pharmacokinetic (PK) analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram per milliliter (mcg/mL) | Pre-dose, hour 1(end of infusion [EOI]), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
|
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| Primary | Maximum Observed Serum Concentration (Cmax) of EMD 525797:After Multiple Dose | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
|
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| Primary | Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Single Dose | Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above Lower limit of quantification (LLQ). | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*mcg/mL | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
|
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| Primary | Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Multiple Dose | Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above LLQ. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*mcg/mL | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Primary | Total Body Clearance (CL) of EMD 525797: After Single Dose | Total body clearance of drug in serum was calculated: as CL= Dose divided by Area under the serum concentration-time curve from time zero to infinity (AUC0-inf). | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
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| Secondary | Number of Subjects With Overall Tumor Response | Overall tumor response was defined as the presence of at least one confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0. Complete response was defined as the disappearance of all target and non-target lesions and normalization of serum levels of tumor markers. PR is at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. | Full analysis set included all subjects who received at least one (non-zero) administration of the trial medication. | Posted | Number | subjects | Baseline up to Week 36 |
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| Secondary | Number of Subjects With Clinical Benefit | Clinical benefit was defined as presence of at least one confirmed CR, PR, or stable disease (SD) lasting at least 12 weeks according to RECIST v1.0. Per RECIST v1.0: CR was defined as disappearance of all target and non-target lesions and normalization of serum levels of tumor markers . PR was defined as >=30% decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non-target lesions. | Full analysis set included all subjects who received at least one (non-zero) administration of the trial medication. | Posted | Number | subjects | Baseline up to Week 36 |
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| Secondary | Progression-free Survival (PFS) | PFS time was defined as the time (in months) from the first dosing date to the date of first documentation of disease progression as reported and documented by the Investigator (i.e. radiological progression per RECIST version 1.0) or death for any cause within 12 weeks after last tumor assessment. Subjects without event are censored on the date of last tumor assessment. | Full analysis set included all subjects who received at least one (non-zero) administration of the trial medication. | Posted | Median | Full Range | months | From first dosing date until disease progression or death, maximum up to Week 36 |
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| Secondary | Apparent Terminal Half Life (t1/2): After Single Dose | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. | Posted | Median | Full Range | hour | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
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| Secondary | Apparent Terminal Half Life (t1/2): After Multiple Dose | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Median | Full Range | hour | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Secondary | Time to Maximum Observed Serum Concentration (Tmax): After Single Dose | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. | Posted | Median | Full Range | hour | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
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| Secondary | Time to Maximum Observed Serum Concentration (Tmax): After Multiple Dose | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Median | Full Range | hour | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Secondary | Elimination Rate Constant (λz): After Single Dose | The elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. | Posted | Geometric Mean | Geometric Coefficient of Variation | per hour | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
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| Secondary | Elimination Rate Constant ( λ z): After Multiple Dose | The elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | per hour | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Secondary | Minimum Observed Serum Concentration (Cmin) After Multiple Doses | The observed minimum serum concentration determined directly from the serum concentration-time profile of each subject. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Secondary | Observed Serum Concentration Immediately Before Next Dosing (Cpre) | The observed serum concentration immediately before next dosing determined directly from the serum concentration-time profile of each subject (= trough concentration) | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Secondary | Average Serum Concentration at Steady State (Cav) | The Cav was calculated by dividing the area under the serum concentration-time curve within one complete dosing interval (AUCtau) by the dosing interval (2 weeks or 336 hoursi.e. Cav =AUCtau/tau). | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Secondary | Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Single Dose | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*mcg/mL | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
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| Secondary | Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Multiple Dose | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*mcg/mL | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Primary | Total Body Clearance at Steady State (CLss) of EMD 525797 | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL of drug in serum was calculated as : CL= Dose/ AUC0-inf. Area under the serum concentration-time curve from time zero to infinity (AUC0-inf), calculated as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Primary | Apparent Volume of Distribution (Vz): After Single Dose | Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by elimination rate constant [λz]) following single dose. Area under the serum concentration-time curve from time zero to infinity, calculated (AUC0-inf) as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant. And the elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data. A minimum of three points is required to calculate λz. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
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| Primary | Pharmacokinetics of EMD 525797 - Trough Values | The observed serum concentration immediately before next dosing determined directly from the serum concentration-time profile of each subject (= trough concentration). | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Primary | Apparent Volume of Distribution: After Multiple Dose | Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/(Area under the serum concentration-time curve within one complete dosing interval [AUCtau]* λz) following multiple dose. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Secondary | Volume of Distribution at Steady State (Vss) | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) was the apparent volume of distribution at steady-state. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Secondary | Mean Residency Time (MRT0-inf) | MRT0-inf of drug in the body was calculated by dividing the area under the first moment curve from time zero to infinity with area under the first moment curve from time zero to infinity minus half of infusion of duration (MRT0-inf = AUMC0-inf/AUMC0-inf - T/2). | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 |
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| Secondary | Mean Residence Time at Steady State (MRTss) | MRTss = (AUMCtau + tau(AUCinf - AUCtau))/ AUCtau) - T/2, where AUMCtau was the area under the first moment curve within one complete dosing interval and T was the infusion duration. Area under the serum concentration-time curve from time zero to infinity, calculated as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Secondary | Percentage Peak-Trough Fluctuation (PTF) | The peak trough fluctuation over one dosing interval at steady state, calculated as PTF (%) = ( [Cmax - Cmin] / Cav ) multiplied by 100. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage fluctuation | Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5 |
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| Secondary | Accumulation Ratio (Rac) | Accumulation ratio for AUC, calculated as area under the serum concentration-time curve within one complete dosing interval at 3rd infusion divided by area under the serum concentration-time curve within one complete dosing interval at 1st infusion. | The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 and Week 5 |
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| 1 |
| 8 |
| 8 |
| 8 |
| EG001 | EMD525797 500 mg | 500 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. | 1 | 6 | 6 | 6 |
| EG002 | EMD525797 1000 mg | 1000 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. | 1 | 6 | 6 | 6 |
| EG003 | EMD525797 1500 mg | 1500 mg of EMD525797 was administered as an intravenous infusion over 1 hour every 2 Weeks until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. | 1 | 7 | 7 | 7 |
| Pneumonia | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
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| Decreased Appetite | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Cancer Pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment |
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| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Iron Deficiency Anaemia | Blood and lymphatic system disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Abdominal Discomfort | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Abdominal Distension | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Abdominal Pain Lower | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Cheilitis | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Enterocolitis | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Drug Hypersensitivity | Immune system disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
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| Gastrointestinal Infection | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 15.0 | Non-systematic Assessment |
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| Alanine Aminotransferase Increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
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| Blood Calcium Increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
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| Blood Creatine Phosphokinase Increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
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| Blood Creatine Phosphokinase Mb Increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
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| Blood Lactate Dehydrogenase Increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
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| Eosinophil Count Increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
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| Fibrin D Dimer Increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
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| Gamma-Glutamyltransferase Increased | Investigations | MedDRA 15.0 | Non-systematic Assessment |
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| Decreased Appetite | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Malnutrition | Metabolism and nutrition disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Cancer Pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment |
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| Tumour Pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Epididymitis | Reproductive system and breast disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Pharyngeal Inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Dermatitis Acneiform | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Haemorrhage Subcutaneous | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Pigmentation Disorder | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Pruritus Generalised | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Rash Generalised | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Skin Fissures | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Non-systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 15.0 | Non-systematic Assessment |
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Not provided
Not provided