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This a Phase III trial designed to determine if IV casopitant plus dexamethasone and ondansetron is more effective in the prevention of vomiting and nausea then dexamethasone and ondansetrone alone following the administration of moderately emetogenic oxaliplatin-based chemotherapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Placebo Comparator | Placebo + standard antiemetics |
|
| Single Dose IV | Experimental | Casopitant + standard antiemetics |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Casopitant | Drug | Experimental NK-1 receptor antagonist |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieved a Complete Response in the Overall Phase (0-120 Hours) Following Initiation of the First Cycle of an Oxaliplatin Based Moderately Emetogenic Chemotherapy (MEC) Regimen | Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. The overall phase began at the start of the administration of the oxaliplatin infusion. Percentage of participants who achieved a complete response in the overall phase (0-120 hours) are presented. | 0 to 120 hours in the first cycle of chemotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieved a Complete Response in the Acute Phase of Cycle 1 | Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. Percentage of participants who achieved a complete response in the acute phase of Cycle 1 are presented. |
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Inclusion Criteria:
A subject will be considered eligible for initial inclusion in this study, and progression into subsequent cycles of therapy within the study, only if all of the following criteria apply:
Subject understands the nature and purpose of this study and the study procedures and has signed an informed consent form for this study to indicate this understanding.
At least 18 years of age.
Is scheduled to receive oxaliplatin at a dose between 85 mg/m² and 130 mg/m² in their first cycle of therapy for the treatment of colorectal cancer, administered as a single IV dose over 2-6 hours on Day 1 only, in combination with 5FU/LV, or in combination with capecitabine.
An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Hematologic and metabolic status adequate for receiving an oxaliplatin-based moderately emetogenic regimen and meeting the following criteria:
Creatinine clearance must be calculated using the Cockcroft-Gault formula:
Clcreat (ml/min) = (140-age [yr]) x body wt [kg] 72 x serum creatinine [mg/dl] For females: multiply creatinine clearance by a factor of 0.85. OR Clcreat (ml/min) = K x (140-age [yr]) x body wt [kg] serum creatinine [µmol/L] K=1.05 for females K=1.23 for males
Liver enzymes must be below the following limits:
Without known liver metastases: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 x ULN.
With known liver metastases: AST and/or ALT ≤5.0 x ULN.
Is willing and able to complete daily components of the Subject Diary for Cycle 1 and Cycle 2 without assistance from others.
A female subject is eligible to enter and participate in this study if she is of:
male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject;
oral contraceptives (e.g., oral, injectable, or implantable) with double-barrier method of contraception consisting of spermicide with either condom or diaphragm for a period after the trial to account for a potential drug interaction (minimum of six weeks);
double-barrier method of contraception consisting of spermicide with either condom or diaphragm;
intra-uterine device with a documented failure rate of less than 1% per year;
complete abstinence from intercourse for two weeks before exposure to the investigational product throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of 3 days);
if subject indicates they will remain abstinent during the period described above, they must agree to follow GSK guidelines for the consistent and correct use of an acceptable method of birth control should they become sexually active.
Exclusion Criteria:
A subject will not be eligible for initial inclusion in this study if any of the following criteria apply, or will not be eligible for subsequent cycles of therapy if any of the following criteria become applicable:
Has received cytotoxic chemotherapy prior to the first study cycle of chemotherapy, with the exception that previous adjuvant therapy with 5FU/LV or capecitabine is permitted, provided that the last dose of adjuvant therapy was completed at least 6 months prior to receiving the first dose of study medication or investigational product. Previous biological or hormonal therapy completed at any time is permitted.
Scheduled to receive chemotherapy with any cytotoxic agents (e.g., irinotecan, gemcitabine) or biological agents (e.g., cetuximab, panitumimab) other than the protocol allowed chemotherapy described in Inclusion Criterion 3.
Is a female subject who is pregnant or lactating.
Has received radiation therapy in the 10 days prior to the first dose of study medication or investigational product and/or is scheduled to receive such radiation therapy in the 6 days following the first dose of study medication or investigational product in the first cycle of chemotherapy. Radiation therapy may be added in subsequent cycles of chemotherapy.
Has experienced emesis (i.e., vomiting and/or retching) or clinically significant nausea in the 24 hours preceding the first dose of study medication or investigational product for each cycle of chemotherapy.
Has known central nervous system metastasis, unless previously successfully treated with excision or radiation, and has been stable for at least 1 week immediately prior to receiving the first dose of study medication or investigational product.
Has increased intracranial pressure, hypercalcemia, an active systemic infection, or any uncontrolled medical condition (other than malignancy) which in the opinion of the Investigator may confound the results of the study, represent another potential etiology for emesis and nausea (other than CINV) or pose an unwarranted risk to the subject.
Has a known hypersensitivity or contraindication to ondansetron, another 5-HT3 receptor antagonist, dexamethasone, or any component of casopitant.
Has received an NK-1 receptor antagonist prior to the first study cycle of chemotherapy.
Has received an investigational drug within the previous 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study medication or investigational product, or is scheduled to receive any investigational drug other than casopitant/placebo during the study period.
Has taken/received any medication of moderate or high emetogenic potential (including antineoplastic agents [see Appendix 2]) within the 48 hours prior to the first dose of study medication or investigational product in each cycle. However, opioid narcotics will be permitted if the subject has been on such medication for at least 7 days at a stable dose prior to the start of each cycle, and has not experienced emesis or nausea from the narcotics.
Has taken/received any medication with known or potential antiemetic activity within the 24-hour period (unless otherwise stated) prior to receiving the first dose of study medication or investigational product or is expected to require use of such medication during the 120 hour assessment period for Cycle 1 of therapy only. This includes, but is not limited to:
Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 for a specified period prior to administration of investigational product in each cycle of therapy.
Has taken/received inducers of CYP3A4 and CYP3A5 within 14 days prior to the administration of investigational product in each cycle of therapy.
Is currently taking, or plans to take the following CYP2C8 substrates at any time during the study: the anti-diabetic agent repaglinide or the diuretic torsemide.
Is currently taking, or plans to take any of the following CYP3A4 substrates at any time during the study: astemizole, cisapride, pimozide, terfenadine.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Hot Springs | Arkansas | 71913 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21822913 | Background | Hesketh PJ, Wright O, Rosati G, Russo M, Levin J, Lane S, Moiseyenko V, Dube P, Kopp M, Makhson A. Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study. Support Care Cancer. 2012 Jul;20(7):1471-8. doi: 10.1007/s00520-011-1235-4. Epub 2011 Aug 7. |
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All participants received ondansetron and dexamethasone as background antiemetic therapy. To assure adequate blinding, placebo to match casopitant was used. Participants were screened within 14 days of first dose of study anti-emetics and were randomly assigned to either single dose intravenous (IV) (90 mg casopitant) or control (placebo).
This study was conducted at 89 centers (55 centers in Europe, 30 in North America and 4 in Korea) in 11 countries from 10-March-2008 to 13-April-2009.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 milligram [mg] twice daily [BID] orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes. |
| FG001 | Casopitant 90 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Dexamethasone |
| Drug |
Standard antiemetics |
|
| Placebo | Drug | Placebo to match IV casopitant |
|
| Ondansetron | Drug | Standard antiemetics |
|
| 0 to 24 hours in the first cycle of chemotherapy |
| Percentage of Participants Who Achieved a Complete Response in the Delayed Phase of Cycle 1 | Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. Percentage of participants who achieved a complete response in the delayed phase of Cycle 1 are presented. | 24 to 120 hours (delayed phase) in the first cycle of chemotherapy |
| Percentage of Participants Who Achieved a Complete Response in the Overall Phase of Cycle 2 | Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. The overall phase began at the start of the administration of the oxaliplatin infusion. Percentage of participants who achieved a complete response in the overall phase of Cycle 2 are presented. | 0 to 120 hours in the second cycle of chemotherapy |
| Maximum Nausea Score, Assessed by a Visual Analogue Scale (VAS) | VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 millimeter (mm) (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
| Percentage of Participants Who Received Rescue Medication | Anti-emetic rescue medication was defined as medication that was administered specifically for the treatment of nausea and/or emesis during Days 1-6 of each cycle. The choice of rescue anti-emetic medication was left to the discretion of the investigator. Participants who required antiemetic rescue medication(s) during the 120-hour assessment period were considered treatment failures for that cycle. Percentage of participants who received rescue medication are presented. | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
| Percentage of Participants Who Vomited and/or Retched | Vomiting was defined as the forceful expulsion of gastrointestinal contents through the mouth or nose. Retching was defined as the labored, spasmodic, rhythmic contraction of the respiratory and abdominal muscles in an attempt to vomit, that is not productive of gastrointestinal contents (also known as dry heaves). If a participant took rescue medication but there was no evidence of vomiting or retching, then the participant was considered as not having vomited. Percentage of participants who vomited and/or retched during the first 120 hours of the first cycle of chemotherapy are presented. | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
| Percentage of Participants Who Reported Significant Nausea, Defined as a Maximum Score >= 25 mm on the VAS | VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 mm (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. Percentage of participants who reported significant nausea, defined as a maximum score >= 25 mm on the VAS are presented. | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
| Percentage of Participants Who Reported Nausea, Defined as a Maximum Score of >= 5 mm on the VAS | VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 mm (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. Percentage of participants who reported nausea, defined as a maximum score of >= 5 mm on the VAS are presented. | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
| Percentage of Participants Who Achieved Complete Protection Defined as Complete Responders With no Significant Nausea | Complete protection was defined as no vomiting/retching, no use of rescue medication and no significant nausea. Percentage of participants who achieved complete protection or complete responders with no significant nausea are presented. | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
| Percentage of Participants Who Achieved Total Control, Defined as Complete Responders Who Had no Nausea | Total control was defined as no vomiting/retching, no use of rescue medication and no nausea. Percentage of participants who achieved total control or complete responders with no nausea are presented. | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
| Percentage of Participants Whose Daily Life Activities Were Impacted in the Overall Phase of Cycle 1, Assessed by Functional Living Index-Emesis (FLIE) Questionnaire | FLIE questionnaire specifically addresses the impact of nausea and vomiting on daily activities (physical, social and emotional function, ability to enjoy meals). It consists of 18 items with questions divided into two domains: Nausea (questions 1-9) and Vomiting (questions 10-18). Each item is scored on a VAS with 7 hatch marks. The scale is anchored at 1 (Not at all) and 7 (A great deal). For questions 1,2,4,5,7,8-10,12-14,16 and 17 the final score was calculated by subtracting the initial score from 100 for questions 3,6,11,15 and 18 the final score was the one provided in the dataset. The score for the nausea domain: ([sum of nausea item scores] ÷ [Number of items answered] x 9) and for vomiting domain: ([sum of vomiting item scores] ÷ [Number of items answered] x 9). The total score was the sum of the nausea and vomiting domain scores. Higher scores indicate less impairment on daily life as a result of nausea or vomiting. | 0 to 120 hours in the first cycle of chemotherapy |
| Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale | Participants were asked to rate the level of nausea he/she experienced over the previous (24 hours for a period of 120 hours following the administration of MEC), by placing a vertical mark on a VAS. The severity of nausea and was calculated by using a 0 - 100 VAS where 0 = No Nausea and 100 = Nausea as bad as it can be. The categorical scale assessed the participants severity of his/her nausea using the following: mild: Queasiness/upset stomach that is manageable and minimally (if at all) affects daily activities, moderate: increased queasiness, sometimes with the feeling of having to vomit/throw up (but not vomiting), that has significant negative effect on the daily activities (for example, being unable to work, eat and drink, prepare food, care for children or others) and severe: feeling sick and vomiting or feeling like you are going to vomit, and unable to perform most daily activities. Higher scores indicated worst outcome. | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
| Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 | Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the electronic case report form (eCRF). Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. AUC(0-∞), AUC(0-t), AUC(0-24) for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented. | Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion |
| Single-dose Pharmacokinetic Parameters: Maximum Observed Drug Concentration (Cmax) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 | Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the electronic case report form (eCRF). Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. (Cmax) for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented. | Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion |
| Single-dose Pharmacokinetic Parameters: Time to Maximum Observed Drug Concentration (Tmax) and Observed Elimination Half-life (t1/2) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 | Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. Tmax and t1/2 for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented. | Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion |
| Single-dose Pharmacokinetic Parameters: Clearance (CL) for Casopitant | Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. CL for casopitant is presented. | Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion |
| Single-dose Pharmacokinetic Parameters: Volume of Distribution (Vdss) for Casopitant | Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. Vdss for casopitant is presented. | Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect. Any SAEs assessed as related to study participation (e.g. study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK product was recorded from the time a participant consents to participate in the study up to and including any follow-up contact. | Up to 35 days |
| Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 | Grade shifts from Baseline were assessed as shift from any Grade to Grade 3 or Grade 4 in any cycle. Toxicities were graded according to the National Cancer Institute common toxicity criteria for adverse events (NCI-CTCAE), version 3.0. Grade refers to the severity of the toxicity. The NCI-CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. It was assessed on Baseline (Day 1), during Day 6-10 and end of cycle. Hematology parameters assessed were hematocrit, hemoglobin, platelet count, total neutrophils and white blood cell count. Data has been presented for the number of participants with hematology toxicity grade shifts from Baseline to toxicity grade 3 and 4 for all cycles in a consolidated format. | Baseline (Day 1) to Day 24 |
| Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 | Grade shifts from Baseline were assessed as shift from any Grade to Grade 3 or Grade 4 in any cycle. Toxicities were graded according to the NCI-CTCAE, version 3.0. Grade refers to the severity of the toxicity. The NCI-CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. It was assessed on Baseline (Day 1), during Day 6-10 and end of cycle. Clinical chemistry parameters assessed were alanine amino transferase (ALT), aspartate amino transferase (AST), chloride, glucose, potassium, sodium and total bilirubin. Data has been presented for the number of participants with chemistry toxicity grade shifts from Baseline to toxicity grade 3 and 4 for all cycles in a consolidated format. | Up to Day 24 |
| Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Vital signs assessment included DBP and SBP. SBP and DBP were recorded at Screening, on Day 1 of each cycle immediately before start of the investigational product infusion, at the completion of the infusion, and immediately after the end of the oxaliplatin infusion, then again at each end of cycle visit. Mean SBP and DBP are presented. | Up to End of Cycle for 6 cycles, an average of 24 days per cycle |
| Evaluation of Vital Signs: Mean Heart Rate | Vital sign included heart rate which was recorded at Screening, on Day 1 of each cycle immediately before start of the investigational product infusion, at the completion of the infusion, and immediately after the end of the oxaliplatin infusion, then again at each end of cycle visit. Mean heart rate is presented. | Up to End of Cycle for 6 cycles, an average of 24 days per cycle |
| Time to First Anti-emetic Rescue Medication | Time to first rescue medication was defined as the length of time from initiation of oxaliplatin till the first reported use of a rescue medication. Participants withdrawing prematurely during the 120 hour assessment period without having received a rescue medication were assumed to have done so and the time of rescue medication was set to 0 hours. The first quartile for time to use of anti-emetic rescue medication was evaluated when 25th percentile of participants of MITT population reported use of anti-emetic rescue medication. Similarly, median and 75th percentile of participants of MITT population was planned to be reported. If, less than 25th percentile of participants reported use of anti-emetic rescue medication at the end of the 120 hour time period, then the observation was censored for the purpose of this analysis and in such case the data was planned to be reported as not evaluable (NA). | 0 to 120 hours in the first cycle of chemotherapy |
| Time to First Emetic Event | Time to first emetic event was defined as the length of time from initiation of oxaliplatin until the time of first emetic event. Participants withdrawing prematurely from the study without having experienced an emetic event were assumed to have done so and the time of emetic event was set to 0 hours. The first quartile for time to emetic event was evaluated when 25th percentile of participants of MITT population reported emetic event. Similarly, median and 75th percentile of participants of MITT population was planned to be reported. If, less than 25th percentile of participants reported emetic event at the end of the 120 hour time period, then the observation was censored for the purpose of this analysis and in such case the data was planned to be reported as not evaluable (NA). | 0 to 120 hours in the first cycle of chemotherapy |
| Corona |
| California |
| 92879 |
| United States |
| GSK Investigational Site | Fountain Valley | California | 92708 | United States |
| GSK Investigational Site | Riverside | California | 92501 | United States |
| GSK Investigational Site | St. Petersburg | Florida | 33705 | United States |
| GSK Investigational Site | Tampa | Florida | 33614 | United States |
| GSK Investigational Site | Alexandria | Louisiana | 71301 | United States |
| GSK Investigational Site | Baton Rouge | Louisiana | 70809 | United States |
| GSK Investigational Site | Baltimore | Maryland | 21215-5271 | United States |
| GSK Investigational Site | Boston | Massachusetts | 02135 | United States |
| GSK Investigational Site | Worcester | Massachusetts | 01608 | United States |
| GSK Investigational Site | Jefferson City | Missouri | 65109 | United States |
| GSK Investigational Site | Great Falls | Montana | 59405 | United States |
| GSK Investigational Site | The Bronx | New York | 10467 | United States |
| GSK Investigational Site | Winston-Salem | North Carolina | 27103 | United States |
| GSK Investigational Site | Hilton Head Island | South Carolina | 29926 | United States |
| GSK Investigational Site | Mt. Pleasant | South Carolina | 29464 | United States |
| GSK Investigational Site | Sumter | South Carolina | 29150 | United States |
| GSK Investigational Site | Corpus Christi | Texas | 78412 | United States |
| GSK Investigational Site | Corpus Christi | Texas | 78463-3069 | United States |
| GSK Investigational Site | Duncanville | Texas | 75137 | United States |
| GSK Investigational Site | Ogden | Utah | 84403 | United States |
| GSK Investigational Site | Burlington | Vermont | 05401 | United States |
| GSK Investigational Site | Assebroek | 8310 | Belgium |
| GSK Investigational Site | Bonheiden | 2820 | Belgium |
| GSK Investigational Site | Ghent | 9000 | Belgium |
| GSK Investigational Site | Ottignies | 1340 | Belgium |
| GSK Investigational Site | Shumen | 9700 | Bulgaria |
| GSK Investigational Site | Sofia | 1756 | Bulgaria |
| GSK Investigational Site | Varna | 9010 | Bulgaria |
| GSK Investigational Site | Sault Ste. Marie | Ontario | P6A 2C4 | Canada |
| GSK Investigational Site | Thunder Bay | Ontario | P7B 6V4 | Canada |
| GSK Investigational Site | Toronto | Ontario | M5G 1X5 | Canada |
| GSK Investigational Site | Charlottetown | Prince Edward Island | C1A 8T5 | Canada |
| GSK Investigational Site | Greenfield Park | Quebec | J4V 2H1 | Canada |
| GSK Investigational Site | Laval | Quebec | H7M 3L9 | Canada |
| GSK Investigational Site | Montreal | Quebec | H1T 2M4 | Canada |
| GSK Investigational Site | Rimouski | Quebec | G5L 5T1 | Canada |
| GSK Investigational Site | Sherbrooke | Quebec | J1H 5N4 | Canada |
| GSK Investigational Site | Brno | 625 00 | Czechia |
| GSK Investigational Site | Brno | 656 91 | Czechia |
| GSK Investigational Site | Chomutov | 430 12 | Czechia |
| GSK Investigational Site | Havlíčkův Brod | 580 22 | Czechia |
| GSK Investigational Site | Prague | 100 00 | Czechia |
| GSK Investigational Site | Prague | 180 81 | Czechia |
| GSK Investigational Site | Semily | 513 01 | Czechia |
| GSK Investigational Site | Freiburg im Breisgau | Baden-Wurttemberg | 79106 | Germany |
| GSK Investigational Site | Ulm | Baden-Wurttemberg | 89081 | Germany |
| GSK Investigational Site | Aschaffenburg | Bavaria | 63739 | Germany |
| GSK Investigational Site | Augsburg | Bavaria | 86150 | Germany |
| GSK Investigational Site | Hof | Bavaria | 95028 | Germany |
| GSK Investigational Site | Munich | Bavaria | 81241 | Germany |
| GSK Investigational Site | Würzburg | Bavaria | 97070 | Germany |
| GSK Investigational Site | Bad Soden | Hesse | 65812 | Germany |
| GSK Investigational Site | Kassel | Hesse | 34119 | Germany |
| GSK Investigational Site | Braunschweig | Lower Saxony | 38114 | Germany |
| GSK Investigational Site | Hanover | Lower Saxony | 30171 | Germany |
| GSK Investigational Site | Essen | North Rhine-Westphalia | 45122 | Germany |
| GSK Investigational Site | Recklinghausen | North Rhine-Westphalia | 45657 | Germany |
| GSK Investigational Site | Würselen | North Rhine-Westphalia | 52146 | Germany |
| GSK Investigational Site | Magdeburg | Saxony-Anhalt | 39104 | Germany |
| GSK Investigational Site | Lübeck | Schleswig-Holstein | 23562 | Germany |
| GSK Investigational Site | Pinneberg | Schleswig-Holstein | 25421 | Germany |
| GSK Investigational Site | Jena | Thuringia | 07743 | Germany |
| GSK Investigational Site | Hamburg | 22081 | Germany |
| GSK Investigational Site | Hamburg | 22457 | Germany |
| GSK Investigational Site | Budapest | 1106 | Hungary |
| GSK Investigational Site | Budapest | 1125 | Hungary |
| GSK Investigational Site | Gyula | 5700 | Hungary |
| GSK Investigational Site | Veszprém | 8200 | Hungary |
| GSK Investigational Site | Potenza | Basilicate | 85100 | Italy |
| GSK Investigational Site | Rionero in Vulture (PZ) | Basilicate | 85028 | Italy |
| GSK Investigational Site | Reggio Calabria | Calabria | 89125 | Italy |
| GSK Investigational Site | Avellino | Campania | 83100 | Italy |
| GSK Investigational Site | Benevento | Campania | 82100 | Italy |
| GSK Investigational Site | Naples | Campania | 80131 | Italy |
| GSK Investigational Site | Genoa | Liguria | 16132 | Italy |
| GSK Investigational Site | Sassari | Sardinia | 07100 | Italy |
| GSK Investigational Site | Catania | Sicily | 95125 | Italy |
| GSK Investigational Site | Florence | Tuscany | 50139 | Italy |
| GSK Investigational Site | Terni | Umbria | 05100 | Italy |
| GSK Investigational Site | Padova | Veneto | 35128 | Italy |
| GSK Investigational Site | Kazan' | 420029 | Russia |
| GSK Investigational Site | Moscow | 115478 | Russia |
| GSK Investigational Site | Moscow | 129 128 | Russia |
| GSK Investigational Site | Moscow Region | 143 423 | Russia |
| GSK Investigational Site | Saint Petersburg | 197758 | Russia |
| GSK Investigational Site | Samara | 443066 | Russia |
| GSK Investigational Site | Banská Bystrica | 975 17 | Slovakia |
| GSK Investigational Site | Bratislava | 833 10 | Slovakia |
| GSK Investigational Site | Košice | 041 91 | Slovakia |
| GSK Investigational Site | Poprad | 058 01 | Slovakia |
| GSK Investigational Site | Gyeonggi-do | 410-769 | South Korea |
| GSK Investigational Site | Seoul | 120-752 | South Korea |
| GSK Investigational Site | Seoul | 135-710 | South Korea |
| GSK Investigational Site | Songpa-gu, Seoul | 138-736 | South Korea |
Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes. |
| COMPLETED |
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| NOT COMPLETED |
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For Age, only 352 participants were analyzed in the Placebo group.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes. |
| BG001 | Casopitant 90 mg | Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age data is presented for modified Intent-to-Treat (mITT) Population which comprised of all participants who were randomized, received any investigational product and had oxaliplatin administered. | N=352 | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Percentage of Participants Who Achieved a Complete Response in the Overall Phase (0-120 Hours) Following Initiation of the First Cycle of an Oxaliplatin Based Moderately Emetogenic Chemotherapy (MEC) Regimen | Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. The overall phase began at the start of the administration of the oxaliplatin infusion. Percentage of participants who achieved a complete response in the overall phase (0-120 hours) are presented. | Modified Intent-to-Treat Population (mITT) comprised of all participants who were randomized, received any investigational product and had oxaliplatin administered. | Posted | Number | Percentage of participants | 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Percentage of Participants Who Achieved a Complete Response in the Acute Phase of Cycle 1 | Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. Percentage of participants who achieved a complete response in the acute phase of Cycle 1 are presented. | MITT Population. | Posted | Number | Percentage of participants | 0 to 24 hours in the first cycle of chemotherapy |
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| Secondary | Percentage of Participants Who Achieved a Complete Response in the Delayed Phase of Cycle 1 | Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. Percentage of participants who achieved a complete response in the delayed phase of Cycle 1 are presented. | MITT Population. | Posted | Number | Percentage of participants | 24 to 120 hours (delayed phase) in the first cycle of chemotherapy |
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| Secondary | Percentage of Participants Who Achieved a Complete Response in the Overall Phase of Cycle 2 | Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. The overall phase began at the start of the administration of the oxaliplatin infusion. Percentage of participants who achieved a complete response in the overall phase of Cycle 2 are presented. | MITT Population. | Posted | Number | Percentage of participants | 0 to 120 hours in the second cycle of chemotherapy |
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| Secondary | Maximum Nausea Score, Assessed by a Visual Analogue Scale (VAS) | VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 millimeter (mm) (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. | MITT Population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Scores on a Scale | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Percentage of Participants Who Received Rescue Medication | Anti-emetic rescue medication was defined as medication that was administered specifically for the treatment of nausea and/or emesis during Days 1-6 of each cycle. The choice of rescue anti-emetic medication was left to the discretion of the investigator. Participants who required antiemetic rescue medication(s) during the 120-hour assessment period were considered treatment failures for that cycle. Percentage of participants who received rescue medication are presented. | MITT Population. | Posted | Number | Percentage of participants | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Percentage of Participants Who Vomited and/or Retched | Vomiting was defined as the forceful expulsion of gastrointestinal contents through the mouth or nose. Retching was defined as the labored, spasmodic, rhythmic contraction of the respiratory and abdominal muscles in an attempt to vomit, that is not productive of gastrointestinal contents (also known as dry heaves). If a participant took rescue medication but there was no evidence of vomiting or retching, then the participant was considered as not having vomited. Percentage of participants who vomited and/or retched during the first 120 hours of the first cycle of chemotherapy are presented. | MITT Population. | Posted | Number | Percentage of participants | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Percentage of Participants Who Reported Significant Nausea, Defined as a Maximum Score >= 25 mm on the VAS | VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 mm (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. Percentage of participants who reported significant nausea, defined as a maximum score >= 25 mm on the VAS are presented. | MITT Population. | Posted | Number | Percentage of participants | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Percentage of Participants Who Reported Nausea, Defined as a Maximum Score of >= 5 mm on the VAS | VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 mm (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. Percentage of participants who reported nausea, defined as a maximum score of >= 5 mm on the VAS are presented. | MITT Population. | Posted | Number | Percentage of participants | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Percentage of Participants Who Achieved Complete Protection Defined as Complete Responders With no Significant Nausea | Complete protection was defined as no vomiting/retching, no use of rescue medication and no significant nausea. Percentage of participants who achieved complete protection or complete responders with no significant nausea are presented. | MITT Population. | Posted | Number | Percentage of participants | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Percentage of Participants Who Achieved Total Control, Defined as Complete Responders Who Had no Nausea | Total control was defined as no vomiting/retching, no use of rescue medication and no nausea. Percentage of participants who achieved total control or complete responders with no nausea are presented. | MITT Population. | Posted | Number | Percentage of participants | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Percentage of Participants Whose Daily Life Activities Were Impacted in the Overall Phase of Cycle 1, Assessed by Functional Living Index-Emesis (FLIE) Questionnaire | FLIE questionnaire specifically addresses the impact of nausea and vomiting on daily activities (physical, social and emotional function, ability to enjoy meals). It consists of 18 items with questions divided into two domains: Nausea (questions 1-9) and Vomiting (questions 10-18). Each item is scored on a VAS with 7 hatch marks. The scale is anchored at 1 (Not at all) and 7 (A great deal). For questions 1,2,4,5,7,8-10,12-14,16 and 17 the final score was calculated by subtracting the initial score from 100 for questions 3,6,11,15 and 18 the final score was the one provided in the dataset. The score for the nausea domain: ([sum of nausea item scores] ÷ [Number of items answered] x 9) and for vomiting domain: ([sum of vomiting item scores] ÷ [Number of items answered] x 9). The total score was the sum of the nausea and vomiting domain scores. Higher scores indicate less impairment on daily life as a result of nausea or vomiting. | MITT Population. | Posted | Number | Percentage of participants | 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale | Participants were asked to rate the level of nausea he/she experienced over the previous (24 hours for a period of 120 hours following the administration of MEC), by placing a vertical mark on a VAS. The severity of nausea and was calculated by using a 0 - 100 VAS where 0 = No Nausea and 100 = Nausea as bad as it can be. The categorical scale assessed the participants severity of his/her nausea using the following: mild: Queasiness/upset stomach that is manageable and minimally (if at all) affects daily activities, moderate: increased queasiness, sometimes with the feeling of having to vomit/throw up (but not vomiting), that has significant negative effect on the daily activities (for example, being unable to work, eat and drink, prepare food, care for children or others) and severe: feeling sick and vomiting or feeling like you are going to vomit, and unable to perform most daily activities. Higher scores indicated worst outcome. | MITT Population. | Posted | Count of Participants | Participants | 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 | Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the electronic case report form (eCRF). Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. AUC(0-∞), AUC(0-t), AUC(0-24) for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented. | PK parameter population: All participants who consented to PK sampling, who were randomized to IV casopitant and for whom a PK sample was obtained and analyzed, and from whom sufficient data was available to calculate casopitant PK parameters on an as-treated basis. Only those participants with data available at indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram/milliliter (hr*ng/mL) | Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion |
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| Secondary | Single-dose Pharmacokinetic Parameters: Maximum Observed Drug Concentration (Cmax) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 | Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the electronic case report form (eCRF). Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. (Cmax) for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented. | PK Parameter population. Only those participants available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter (ng/mL) | Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion |
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| Secondary | Single-dose Pharmacokinetic Parameters: Time to Maximum Observed Drug Concentration (Tmax) and Observed Elimination Half-life (t1/2) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 | Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. Tmax and t1/2 for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented. | PK parameter population. Only those participants available at the specified time points were analyzed. | Posted | Median | Full Range | Hour | Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion |
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| Secondary | Single-dose Pharmacokinetic Parameters: Clearance (CL) for Casopitant | Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. CL for casopitant is presented. | PK Parameter Population. Only those participants available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter/hour | Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion |
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| Secondary | Single-dose Pharmacokinetic Parameters: Volume of Distribution (Vdss) for Casopitant | Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. Vdss for casopitant is presented. | PK Parameter Population. Only those participants available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion |
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| Secondary | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect. Any SAEs assessed as related to study participation (e.g. study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK product was recorded from the time a participant consents to participate in the study up to and including any follow-up contact. | Safety Population which comprised of all participants who were randomized, and received any investigational product. | Posted | Count of Participants | Participants | Up to 35 days |
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| Secondary | Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 | Grade shifts from Baseline were assessed as shift from any Grade to Grade 3 or Grade 4 in any cycle. Toxicities were graded according to the National Cancer Institute common toxicity criteria for adverse events (NCI-CTCAE), version 3.0. Grade refers to the severity of the toxicity. The NCI-CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. It was assessed on Baseline (Day 1), during Day 6-10 and end of cycle. Hematology parameters assessed were hematocrit, hemoglobin, platelet count, total neutrophils and white blood cell count. Data has been presented for the number of participants with hematology toxicity grade shifts from Baseline to toxicity grade 3 and 4 for all cycles in a consolidated format. | Safety Population. | Posted | Count of Participants | Participants | Baseline (Day 1) to Day 24 |
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| Secondary | Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 | Grade shifts from Baseline were assessed as shift from any Grade to Grade 3 or Grade 4 in any cycle. Toxicities were graded according to the NCI-CTCAE, version 3.0. Grade refers to the severity of the toxicity. The NCI-CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. It was assessed on Baseline (Day 1), during Day 6-10 and end of cycle. Clinical chemistry parameters assessed were alanine amino transferase (ALT), aspartate amino transferase (AST), chloride, glucose, potassium, sodium and total bilirubin. Data has been presented for the number of participants with chemistry toxicity grade shifts from Baseline to toxicity grade 3 and 4 for all cycles in a consolidated format. | Safety Population. | Posted | Count of Participants | Participants | Up to Day 24 |
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| Secondary | Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Vital signs assessment included DBP and SBP. SBP and DBP were recorded at Screening, on Day 1 of each cycle immediately before start of the investigational product infusion, at the completion of the infusion, and immediately after the end of the oxaliplatin infusion, then again at each end of cycle visit. Mean SBP and DBP are presented. | Safety Population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Millimeters of mercury (mmHg) | Up to End of Cycle for 6 cycles, an average of 24 days per cycle |
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| Secondary | Evaluation of Vital Signs: Mean Heart Rate | Vital sign included heart rate which was recorded at Screening, on Day 1 of each cycle immediately before start of the investigational product infusion, at the completion of the infusion, and immediately after the end of the oxaliplatin infusion, then again at each end of cycle visit. Mean heart rate is presented. | Safety Population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Beats/minute | Up to End of Cycle for 6 cycles, an average of 24 days per cycle |
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| Secondary | Time to First Anti-emetic Rescue Medication | Time to first rescue medication was defined as the length of time from initiation of oxaliplatin till the first reported use of a rescue medication. Participants withdrawing prematurely during the 120 hour assessment period without having received a rescue medication were assumed to have done so and the time of rescue medication was set to 0 hours. The first quartile for time to use of anti-emetic rescue medication was evaluated when 25th percentile of participants of MITT population reported use of anti-emetic rescue medication. Similarly, median and 75th percentile of participants of MITT population was planned to be reported. If, less than 25th percentile of participants reported use of anti-emetic rescue medication at the end of the 120 hour time period, then the observation was censored for the purpose of this analysis and in such case the data was planned to be reported as not evaluable (NA). | MITT Population. | Posted | Median | Inter-Quartile Range | Hours | 0 to 120 hours in the first cycle of chemotherapy |
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| Secondary | Time to First Emetic Event | Time to first emetic event was defined as the length of time from initiation of oxaliplatin until the time of first emetic event. Participants withdrawing prematurely from the study without having experienced an emetic event were assumed to have done so and the time of emetic event was set to 0 hours. The first quartile for time to emetic event was evaluated when 25th percentile of participants of MITT population reported emetic event. Similarly, median and 75th percentile of participants of MITT population was planned to be reported. If, less than 25th percentile of participants reported emetic event at the end of the 120 hour time period, then the observation was censored for the purpose of this analysis and in such case the data was planned to be reported as not evaluable (NA). | MITT Population. | Posted | Median | Inter-Quartile Range | Hours | 0 to 120 hours in the first cycle of chemotherapy |
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Up to 35 days.
SAE and non-SAE were collected and are reported for the Safety Population.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes. | 5 | 352 | 23 | 352 | 237 | 352 |
| EG001 | Casopitant 90 mg | Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes. | 4 | 355 | 26 | 355 | 257 | 355 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Ileus | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Rectal haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Duodenal ulcer | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Gastrointestinal obstruction | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Deep vein thrombosis | Vascular disorders | MedDRA | Systematic Assessment |
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| Thrombosis | Vascular disorders | MedDRA | Systematic Assessment |
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| Hypertensive crisis | Vascular disorders | MedDRA | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
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| Hypovolaemic shock | Vascular disorders | MedDRA | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA | Systematic Assessment |
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| Venous thrombosis | Vascular disorders | MedDRA | Systematic Assessment |
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| Angina unstable | Cardiac disorders | MedDRA | Systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Atrioventricular block complete | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiopulmonary failure | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiovascular disorder | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Catheter related infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Febrile infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Sudden death | General disorders | MedDRA | Systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Tumour compression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Ureteric stenosis | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D009325 | Nausea |
| D014839 | Vomiting |
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C531951 | casopitant |
| D003907 | Dexamethasone |
| D017294 | Ondansetron |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006575 | Heterocyclic Compounds, 3-Ring |
Not provided
Not provided
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| Participants |
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| Participants |
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| Units |
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| Participants |
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| Participants |
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Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
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| Units | Counts |
|---|---|
| Participants |
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| Moderate |
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| Severe |
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| Moderate |
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| Severe |
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