Symptoms and General Pathology

All Conditions

Nausea

Vomiting

Signs and Symptoms, Digestive

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dermatologic Agents

Dexamethasone

Ondansetron

Oxaliplatin

Dexamethasone acetate

Casopitant

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Serotonin

Serotonin 5-HT3 Receptor Antagonists

Neurotransmitter Agents

Neurokinin-1 Receptor Antagonists

Substance P

Neurokinin A

Placebo

GSK Clinical Trials

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.

A Study Of IV Casopitant For The Prevention Of Chemotherapy Induced Nausea And Vomiting.

A Study of Single Dose Intravenous Casopitant in Combination With Ondansetron and Dexamethasone for the Prevention of Oxaliplatin Induced Nausea and Vomiting.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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).

GlaxoSmithKline

SAE and non-SAE were collected and are reported for the Safety Population.

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.

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.

Casopitant 90 mg

Total

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.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

For Age, only 352 participants were analyzed in the Placebo group.

GSK Response Center

Modified Intent-to-Treat Population (mITT) comprised of all participants who were randomized, received any investigational product and had oxaliplatin administered.

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

Percentage of Participants Who Achieved a Complete Response in the Acute Phase of Cycle 1

Percentage of Participants Who Achieved a Complete Response in the Delayed Phase of Cycle 1

Percentage of Participants Who Achieved a Complete Response in the Overall Phase of Cycle 2

Placebo vs Casopitant 90 mg (0-120 hours)

Placebo vs Casopitant 90 mg (24-120 hours)

0-120 hours

0-24 hours

24-120 hours

MITT Population. Only those participants available at the specified time points were analyzed.

Maximum Nausea Score, Assessed by a Visual Analogue Scale (VAS)

Percentage of Participants Who Received Rescue Medication

Percentage of Participants Who Vomited and/or Retched

Percentage of Participants Who Reported Significant Nausea, Defined as a Maximum Score >= 25 mm on the VAS

Percentage of Participants Who Reported Nausea, Defined as a Maximum Score of >= 5 mm on the VAS

Percentage of Participants Who Achieved Complete Protection Defined as Complete Responders With no Significant Nausea

Percentage of Participants Who Achieved Total Control, Defined as Complete Responders Who Had no Nausea

Nausea Impact: Placebo vs. Casopitant 90 mg; Cycle 1 (0-120 hours)

Vomiting Impact: Placebo vs. Casopitant 90 mg; Cycle 1 (0-120 hours)

Nausea impact

Vomiting impact

Percentage of Participants Whose Daily Life Activities Were Impacted in the Overall Phase of Cycle 1, Assessed by Functional Living Index-Emesis (FLIE) Questionnaire

Placebo vs. Casopitant 90 mg: (0-120 hours) in Cycle 1

Placebo vs. Casopitant 90 mg: (0-24 hours) in Cycle 1

Placebo vs. Casopitant 90 mg: (24-120 hours) in Cycle 1

Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale

Casopitant: AUC(0-24)

Casopitant: AUC(0-inf)

Casopitant: AUC(0-t)

GSK525060: AUC(0-24)

GSK525060: AUC(0-t)

GSK517142: AUC(0-24)

GSK517142: AUC(0-t)

GSK631832: AUC(0-24)

GSK631832: AUC(0-t)

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.

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

GSK525060

GSK517142

GSK631832

PK Parameter population. Only those participants available at the specified time points were analyzed.

Single-dose Pharmacokinetic Parameters: Maximum Observed Drug Concentration (Cmax) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832

Casopitant: Tmax

Casopitant: t1/2

GSK525060: Tmax

GSK517142: Tmax

GSK631832: Tmax

PK parameter population. Only those participants available at the specified time points were analyzed.

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

PK Parameter Population. Only those participants available at the specified time points were analyzed.

Single-dose Pharmacokinetic Parameters: Clearance (CL) for Casopitant

Single-dose Pharmacokinetic Parameters: Volume of Distribution (Vdss) for Casopitant

Safety Population which comprised of all participants who were randomized, and received any investigational product.

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

Hematocrit: All cycles, Grade 2 to Grade 3

Hemoglobin: All cycles, Grade 1 to Grade 3

Hemoglobin: All cycles, Grade 2 to Grade 3

Hemoglobin: All cycles, Grade 3 to Grade 3

Platelet count: All cycles, Grade 0 to 3

Total Neutrophils: All cycles, Grade 0 to 3

Total Neutrophils: All cycles, Grade 1 to 3

Total Neutrophils: All cycles, Grade 2 to 3

White Blood Cell count: All cycles, Grade 0 to 3

White Blood Cell count: All cycles, Grade 1 to 3

White Blood Cell count: All cycles, Grade 2 to 3

Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4

ALT: All cycles, Grade 0 to 3

ALT: All cycles, Grade 2 to 3

AST: All cycles, Grade 0 to 3

High chloride: All cycles, Grade 1 to 3

Low chloride: All cycles, Grade 0 to 3

Hyperglycemia: Al cycles, Grade 0 to 3

Hyperglycemia: All cycles, Grade 1 to 3

Hyperglycemia: All cycles, Grade 2 to 3

Hyperglycemia: All cycles, Grade 3 to 3

Hypoglycemia: All cycles, Grade 0 to 4

Hyperkalemia: All cycles, Grade 2 to 3

Hyperkalemia: All cycles, Grade 4 to 3

Hyperkalemia: All cycles, Grade 0 to 3

Hyperkalemia: All cycles, Grade 0 to 4

Hypokalemia: All cycles, Grade 0 to 3

Hyponatremia: All cycles, Grade 1 to 3

Total Bilirubin: All cycles, Grade 0 to 3

Total Bilirubin: All cycles, Grade 0 to 4

Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4

DBP: Cycle 1, post-oxaliplatin

DBP: Cycle 1, End of cycle

DBP: Cycle 2, post-oxaliplatin

DBP: Cycle 2, End of cycle

DBP: Cycle 3, post-oxaliplatin

DBP: Cycle 3, End of cycle

DBP: Cycle 4, post-oxaliplatin

DBP: Cycle 4, End of cycle

DBP: Cycle 5, post-oxaliplatin

DBP: Cycle 5, End of cycle

DBP: Cycle 6, post-oxaliplatin

DBP: Cycle 6, End of cycle

SBP: Cycle 1, post-oxaliplatin

SBP: Cycle 1, End of cycle

SBP: Cycle 2, post-oxaliplatin

SBP: Cycle 2, End of cycle

SBP: Cycle 3, post-oxaliplatin

SBP: Cycle 3, End of cycle

SBP: Cycle 4, post-oxaliplatin

SBP: Cycle 4, End of cycle

SBP: Cycle 5, post-oxaliplatin

SBP: Cycle 5, End of cycle

SBP: Cycle 6, post-oxaliplatin

SBP: Cycle 6, End of cycle

Safety Population. Only those participants available at the specified time points were analyzed.

Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Cycle 1, post-oxaliplatin

Cycle 1, End of cycle

Cycle 2, post-oxaliplatin

Cycle 2, End of cycle

Cycle 3, post-oxaliplatin

Cycle 3, End of cycle

Cycle 4, post-oxaliplatin

Cycle 4, End of cycle

Cycle 5, post-oxaliplatin

Cycle 5, End of cycle

Cycle 6, post-oxaliplatin

Cycle 6, End of cycle

Evaluation of Vital Signs: Mean Heart Rate

Time to First Anti-emetic Rescue Medication

Time to First Emetic Event

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Of IV Casopitant For The Prevention Of Chemotherapy Induced Nausea And Vomiting.	NCT00601172	Nausea and Vomi...	Casopitant Dexamethasone Placebo Ondansetron	18 Years -	GlaxoSmithKline
A Study Of IV Casopitant For The Prevention Of Chemotherapy Induced Nausea And Vomiting.	NCT00601172	Nausea and Vomi...	Casopitant Dexamethasone Placebo Ondansetron	18 Years -	GlaxoSmithKline
A Study Of IV Casopitant For The Prevention Of Chemotherapy Induced Nausea And Vomiting.	NCT00601172	Nausea and Vomi...	Casopitant Dexamethasone Placebo Ondansetron	18 Years -	GlaxoSmithKline
A Study Of IV Casopitant For The Prevention Of Chemotherapy Induced Nausea And Vomiting.	NCT00601172	Nausea and Vomi...	Casopitant Dexamethasone Placebo Ondansetron	18 Years -	GlaxoSmithKline

Spots Global Cancer Trial Database for casopitant

Every month we try and update this database with for casopitant cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for casopitant

Every month we try and update this database with for casopitant cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for casopitant cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.