A Phase 1 interventional study of MSC2015103B and MSC2015103B in Advanced Solid Tumor, sponsored by EMD Serono. Terminated at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-05-08.
Sponsored by EMD Serono · Phase 1, Interventional, and Treatment
The main purpose of this study is to test the experimental drug, MSC2015103B at different dose levels and on different treatment schedules, to see whether it is safe and can be tolerated when given to subjects once a day one day per week over a 21-day period or once a day three times per week over a 21-day period. The investigators would also like to find out how MSC2015103B is broken down by the body.
Additional purposes of the trial are to assess side effects of MSC2015103B and to find out whether MSC2015103B has anti-cancer effects. In addition, the investigators would like to explore pharmacokinetics.
9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.
This study's enrollment of 28 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →EMD Serono is the lead sponsor of 88 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Other inclusion criteria as defined in protocol.
Exclusion Criteria
Drug: MSC2015103B
Drug: MSC2015103B
Schedule 1: MSC2015103B will be administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD establishment. Starting dose will be 150 microgram (mcg), which will be escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.
Schedule 2: MSC2015103B will be administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose will be 150 mcg, and will be escalated to 200 mcg subsequently.
Number of Subjects Who Experienced Dose-limiting Toxicities (DLT)
DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to progressive disease (PD) at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (\>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition.
Time frame: Up to Day 21 of Cycle 1
Percentage of Subjects Who Experienced DLT
DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to PD at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (\>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition.
Time frame: Up to Day 21 of Cycle 1
Percentage of Subjects Who Experienced Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. SAE (Serious adverse event) is defined as any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.. TEAEs are events between first dose of study drug up to the cut-off date (15 July 2013) and were absent before treatment or that worsened relative to pretreatment state.
Time frame: From the initiation of the trial till the data cut-off date 15 July 2013
Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication
Abnormal laboratory findings and other abnormal investigational findings which were associated with clinical signs and symptoms, lead to treatment discontinuation, or considered medically important by the investigator were reported as AEs.
Time frame: From the initiation of the trial till the data cut-off date 15 July 2013
Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication
Abnormal laboratory findings and other abnormal investigational findings which were associated with clinical signs and symptoms, lead to treatment discontinuation, or considered medically important by the investigator were reported as AEs.
Time frame: From the initiation of the trial till the data cut-off date 15 July 2013
Maximum Plasma Concentration (Cmax)
Time frame: Schedule 1 : 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Days 1 and 17.
Time to Reach Maximum Plasma Concentration (Tmax)
Time frame: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.
Apparent Terminal Half Life (T1/2)
The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination.
Time frame: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.
Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-inf])
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Time frame: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.
AUC Versus Time Curve Within One Dosing Interval (AUC0-tau)
Time frame: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.
Apparent Oral Clearance of the Drug From Plasma (CL/f)
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/f was influenced by the fraction absorbed.
Time frame: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1.
Apparent Volume of Distribution Associated to the Terminal Phase (Vz/f)
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 serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.
Time frame: Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1.
Extracellular Signal-regulated Kinase (ERK) Phosphorylation Levels
ERK phosphorylation levels were to be assessed in peripheral blood mononuclear cells (PBMC) during the dose escalation
Time frame: Schedule 1: Day 1: Pre-dose; Post-dose: 2, 4, 8, 24 hour; 48 or 72 hour; 48 or 96 hour, 168 hour; Day 15: Pre-dose; Schedule 2: Day 1: Pre-dose; Post-dose: 2, 8, 24, 48, 96 hour; Day 15: Pre-dose; Day 17: Pre-dose; Post-dose: 2, 8, and 24 hour
Percentage of Subjects With Overall Response
Overall response was to be confirmed by complete response (CR) or partial response (PR) using response evaluation criteria in solid tumours Version 1.0 (RECIST) during treatment. CR: The disappearance of all target and non-target lesions and normalization of tumor marker level; PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline.
Time frame: Every 6 Weeks until complete response or till data cut-off date 15 July 2013
Percentage of Subjects With Clinical Benefit
Clinical benefit was to be confirmed by CR, PR or stable disease (SD) lasting at least 6 weeks (using RECIST v1.0) during treatment. CR: The disappearance of all target and non-target lesions and normalization of tumor marker level; PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started.
Time frame: Every 6 Weeks until complete response or till data cut-off date 15 July 2013
First/Last subject (informed consent): 09 September 2011/18 April 2013. Study completion date: 15 July 2013, Clinical data cut-off date: 15 July 2013; Subjects were randomized at 3 centers in United States.
| Milestone | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Started | 21 | 7 |
| Completed | 21 | 7 |
| Not completed | 0 | 0 |
DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to progressive disease (PD) at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (\>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition.
| Subjects | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Number of Subjects Who Experienced Dose-limiting Toxicities (DLT) | 0 | 0 |
DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to PD at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (\>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition.
| Percentage of subjects | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Percentage of Subjects Who Experienced DLT | 0 | 0 |
An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. SAE (Serious adverse event) is defined as any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.. TEAEs are events between first dose of study drug up to the cut-off date (15 July 2013) and were absent before treatment or that worsened relative to pretreatment state.
| Percentage of subjects | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| TEAEs | 100.0 | 100.0 |
| Serious TEAEs | 19.0 | 42.9 |
| TEAEs leading to death | 0.0 | 0.0 |
| TEAEs leading to discontinuation | 0.0 | 14.3 |
Abnormal laboratory findings and other abnormal investigational findings which were associated with clinical signs and symptoms, lead to treatment discontinuation, or considered medically important by the investigator were reported as AEs.
| Percentage of subjects | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Aspartate aminotransferase increased | 14.3 | 0.0 |
| Decreased appetite | 14.3 | 14.3 |
| Gamma-glutamyl transferase increased | 0.0 | 14.3 |
| Blood alkaline phosphatase increased | 0.0 | 14.3 |
| Ejection fraction decreased | 0.0 | 14.3 |
| Blood glucose increased | 0.0 | 14.3 |
| Hypokalemia | 0.0 | 28.6 |
| Hyponatraemia | 0.0 | 28.6 |
| Hypoalbuminaemia | 0.0 | 14.3 |
| Hypophosphatemia | 0.0 | 14.3 |
Abnormal laboratory findings and other abnormal investigational findings which were associated with clinical signs and symptoms, lead to treatment discontinuation, or considered medically important by the investigator were reported as AEs.
| Subjects | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Aspartate aminotransferase increased | 3 | 0 |
| Decreased appetite | 3 | 1 |
| Gamma-glutamyl transferase increased | 0 | 1 |
| Blood alkaline phosphatase increased | 0 | 1 |
| Ejection fraction decreased | 0 | 1 |
| Blood glucose increased | 0 | 1 |
| Hypokalemia | 0 | 2 |
| Hyponatraemia | 0 | 2 |
| Hypoalbuminaemia | 0 | 1 |
| Hypophosphatemia | 0 | 1 |
| Picogram per milliliter | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Week 1 (n=3, 4, 3, 3, 3, 3, 2, 3, 4) | 38.750 (25.20 to 58.90) | 38.110 (25.40 to 56.70) | 97.293 (34.40 to 179.2) | 290.98 (199.1 to 441.0) | 396.45 (193.7 to 657.2) | 888.15 (295.0 to 3010) | 2215.9 (1760 to 2790) | 75.313 (55.60 to 98.50) | 52.331 (33.4 to 72.7) |
| Week 2 (n= 3,3,3,3,1,3,2,2,3) | 48.952 (29.70 to 82.80) | 63.732 (54.50 to 74.80) | 219.71 (108.1 to 336.1) | 329.62 (257.3 to 439.5) | 2471.0 (2471 to 2471) | 1728.1 (835.0 to 2630) | 5636.8 (5340 to 5950) | 190.59 (141.4 to 256.9) | 157.62 (80.10 to 404.0) |
| Hour | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Week 1 (n=3,4,3,3,3,3,2,3,4) | 2.4478 (1.833 to 4.000) | 5.2643 (4.000 to 8.000) | 1.4422 (1.000 to 2.000) | 1.4422 (1.000 to 2.000) | 1.5874 (1.000 to 4.0000) | 1.1447 (0.500 to 2.000) | 1.2450 (1.033 to 1.500) | 2.4248 (1.500 to 6.067) | 1.3161 (1.000 to 2.000) |
| Week 3 (n=3,3,3,3,1,3,2,2,3) | 1.1573 (1.000 to 1.500) | 2.3833 (1.500 to 6.017) | 4.5789 (2.000 to 8.000) | 1.1635 (1.000 to 1.500) | 0.50000 (0.5000 to 0.5000) | 2.0110 (1.017 to 4.000) | 0.70711 (0.5000 to 1.000) | 2.8519 (2.033 to 4.000) | 1.6869 (1.500 to 2.133) |
The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination.
| Hour | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Week 1 (n=3,4,3,3,3,3,2,3,4) | 134.88 (72.76 to 201.9) | 115.41 (73.51 to 280.2) | 55.023 (20.85 to 118.7) | 53.072 (51.51 to 55.10) | 115.34 (85.23 to 135.4) | 52.852 (49.40 to 58.26) | 81.124 (33.51 to 196.4) | 30.850 (23.55 to 40.09) | 33.007 (22.74 to 46.98) |
| Week 3 (n=3,3,3,3,1,3,2,2,3) | 102.30 (41.27 to 251.3) | 102.53 (76.49 to 122.5) | 138.47 (115.5 to 191.1) | 55.43 (42.21 to 85.54) | 37.16 (37.16 to 37.16) | 103.77 (55.95 to 185.7) | 100.91 (91.41 to 111.4) | 121.58 (49.19 to 300.5) | 145.70 (56.03 to 643.5) |
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
| Hour*picogram/milliliter | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Week 1 (n=3,4,3,3,3,3,2,3,4) | 3644.7 (1997 to 6477) | 3927.4 (2513 to 5479) | 2249.9 (829.0 to 4037) | 7890.1 (6454 to 10920) | 12454 (8921 to 23730) | 13164 (6049 to 19880) | 23558 (18580 to 29870) | 2032.2 (1408 to 3234) | 1375.2 (948.0 to 2377) |
| Week 3 (n=,3,3,3,3,1,3,2,2,3) | 4715.2 (1710 to 17490) | 4377.2 (3552 to 6006) | 16465 (7797 to 38300) | 12397 (7532 to 16750) | 24580 (24580 to 24580) | 35423 (14410 to 68400) | 66081 (61480 to 71020) | 21735 (6093 to 77530) | 14870 (7409 to 27350) |
| hours*picogram/milliliter | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Week 1 (n=3,4,3,3,3,3,2,3,4) | 2072.8 (1549 to 2789) | 2381.6 (1947 to 3892) | 1752.7 (725.1 to 3202) | 6824.4 (5577 to 9363) | 8434.6 (6120 to 13990) | 11533 (5498 to 17850) | 17698 (16630 to 18830) | 1345.3 (1073 to 1809) | 865.76 (738.5 to 1231) |
| Week 3 (n=3,3,3,3,1,3,2,2,3) | 2946.9 (1645 to 6147) | 3002.0 (2525 to 3810) | 8865.3 (4920 to 16490) | 10696 (7208 to 15580) | 23670 (23670 to 23670) | 25150 (12190 to 40520) | 47114 (44670 to 49690) | 4993.3 (2984 to 8356) | 3070.5 (1661 to 7338) |
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/f was influenced by the fraction absorbed.
| Liter/hour | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Apparent Oral Clearance of the Drug From Plasma (CL/f) | 41.156 (23.16 to 75.11) | 50.924 (36.51 to 79.57) | 133.34 (74.30 to 361.9) | 57.033 (41.19 to 69.73) | 52.192 (27.39 to 72.86) | 75.968 (50.29 to 165.3) | 63.673 (50.22 to 80.73) | 73.813 (46.38 to 106.6) | 145.44 (84.15 to 211.0) |
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 serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.
| Liter | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Apparent Volume of Distribution Associated to the Terminal Phase (Vz/f) | 8008.6 (6746 to 9658) | 8478.7 (4275 to 14760) | 10584 (7219 to 15090) | 4366.9 (3275 to 5298) | 8684.7 (5349 to 13670) | 5792.4 (3722 to 11780) | 7452.2 (3903 to 14230) | 3285.2 (2682 to 3651) | 6925.6 (5704 to 8253) |
ERK phosphorylation levels were to be assessed in peripheral blood mononuclear cells (PBMC) during the dose escalation
No measurements were reported for this outcome.
Overall response was to be confirmed by complete response (CR) or partial response (PR) using response evaluation criteria in solid tumours Version 1.0 (RECIST) during treatment. CR: The disappearance of all target and non-target lesions and normalization of tumor marker level; PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline.
| percentage of subjects | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| CR | 0 | 0 |
| PR | 0 | 0 |
Clinical benefit was to be confirmed by CR, PR or stable disease (SD) lasting at least 6 weeks (using RECIST v1.0) during treatment. CR: The disappearance of all target and non-target lesions and normalization of tumor marker level; PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started.
| percentage of subjects | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Percentage of Subjects With Clinical Benefit | 33.3 | 28.6 |
Collected over From the initiation of the trial till data cut-off date (15 July 2013). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1 - MSC2015103B (Schedule 1) | — | 4/21 (19%) | 21/21 (100%) |
| Part 1 - MSC2015103B (Schedule 2) | — | 3/7 (42.9%) | 7/7 (100%) |
| Event | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| NauseaGastrointestinal disorders | 0/21 | 1/7 |
| VomitingGastrointestinal disorders | 0/21 | 1/7 |
| PneumoniaInfections and infestations | 1/21 | 1/7 |
| Catheter site infectionInfections and infestations | 0/21 | 1/7 |
| Feeding tube complicationInjury, poisoning and procedural complications | 0/21 | 1/7 |
| Abdominal painGastrointestinal disorders | 1/21 | 0/7 |
| Septic shockInfections and infestations | 1/21 | 0/7 |
| HypokalaemiaMetabolism and nutrition disorders | 1/21 | 0/7 |
| HaematuriaRenal and urinary disorders | 1/21 | 0/7 |
| NephrolithiasisRenal and urinary disorders | 1/21 | 0/7 |
| Event | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| ConstipationGastrointestinal disorders | 1/21 | 3/7 |
| NauseaGastrointestinal disorders | 3/21 | 3/7 |
| FatigueGeneral disorders | 9/21 | 2/7 |
| HypokalaemiaMetabolism and nutrition disorders | 2/21 | 3/7 |
| HyponatraemiaMetabolism and nutrition disorders | 1/21 | 3/7 |
| DiarrhoeaGastrointestinal disorders | 6/21 | 0/7 |
| PyrexiaGeneral disorders | 1/21 | 2/7 |
| Urinary tract infectionInfections and infestations | 1/21 | 2/7 |
| Aspartate aminotransferase increasedInvestigations | 6/21 | 0/7 |
| Decreased appetiteMetabolism and nutrition disorders | 6/21 | 1/7 |
Safety analysis set included all subjects who received at least one administration of the trial medication.
| Age, Customized(Subjects) | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) | Total |
|---|---|---|---|
| 18 to less than (<) 45 years | 2 | 0 | 2 |
| Greater than equal to (>=) 45 to <65 years | 10 | 5 | 15 |
| >=65 years | 9 | 2 | 11 |
| Sex: Female, Male(Participants) | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) | Total |
|---|---|---|---|
| Female | 4 | 4 | 8 |
| Male | 17 | 3 | 20 |
This study is terminated, as verified in Mar 2017. You cannot join it, but the record below documents what was studied.
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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
EMD Serono