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.

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.

Study Overview

• Status: Completed
• Conditions: Nausea and Vomiting, Chemotherapy-Induced
• Intervention / Treatment: Drug: Dexamethasone; Drug: Placebo; Drug: Ondansetron; Drug: Casopitant

• Study Type: Interventional
• Enrollment (Actual): 710
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Assebroek, Belgium, 8310
    • GSK Investigational Site
  • Bonheiden, Belgium, 2820
    • GSK Investigational Site
  • Gent, Belgium, 9000
    • GSK Investigational Site
  • Ottignies, Belgium, 1340
    • GSK Investigational Site
• Bulgaria
  • Shumen, Bulgaria, 9700
    • GSK Investigational Site
  • Sofia, Bulgaria, 1756
    • GSK Investigational Site
  • Varna, Bulgaria, 9010
    • GSK Investigational Site
• Canada
  • Ontario
    • Sault Ste. Marie, Ontario, Canada, P6A 2C4
      • GSK Investigational Site
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 1X5
      • GSK Investigational Site
  • Prince Edward Island
    • Charlottetown, Prince Edward Island, Canada, C1A 8T5
      • GSK Investigational Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • GSK Investigational Site
    • Laval, Quebec, Canada, H7M 3L9
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H1T 2M4
      • GSK Investigational Site
    • Rimouski, Quebec, Canada, G5L 5T1
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • GSK Investigational Site
• Czechia
  • Brno, Czechia, 625 00
    • GSK Investigational Site
  • Brno, Czechia, 656 91
    • GSK Investigational Site
  • Chomutov, Czechia, 430 12
    • GSK Investigational Site
  • Havlickuv Brod, Czechia, 580 22
    • GSK Investigational Site
  • Praha 10, Czechia, 100 00
    • GSK Investigational Site
  • Praha 8, Czechia, 180 81
    • GSK Investigational Site
  • Semily, Czechia, 513 01
    • GSK Investigational Site
• Germany
  • Hamburg, Germany, 22457
    • GSK Investigational Site
  • Hamburg, Germany, 22081
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79106
      • GSK Investigational Site
    • Ulm, Baden-Wuerttemberg, Germany, 89081
      • GSK Investigational Site
  • Bayern
    • Aschaffenburg, Bayern, Germany, 63739
      • GSK Investigational Site
    • Augsburg, Bayern, Germany, 86150
      • GSK Investigational Site
    • Hof, Bayern, Germany, 95028
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 81241
      • GSK Investigational Site
    • Wuerzburg, Bayern, Germany, 97070
      • GSK Investigational Site
  • Hessen
    • Bad Soden, Hessen, Germany, 65812
      • GSK Investigational Site
    • Kassel, Hessen, Germany, 34119
      • GSK Investigational Site
  • Niedersachsen
    • Braunschweig, Niedersachsen, Germany, 38114
      • GSK Investigational Site
    • Hannover, Niedersachsen, Germany, 30171
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45122
      • GSK Investigational Site
    • Recklinghausen, Nordrhein-Westfalen, Germany, 45657
      • GSK Investigational Site
    • Wuerselen, Nordrhein-Westfalen, Germany, 52146
      • GSK Investigational Site
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39104
      • GSK Investigational Site
  • Schleswig-Holstein
    • Luebeck, Schleswig-Holstein, Germany, 23562
      • GSK Investigational Site
    • Pinneberg, Schleswig-Holstein, Germany, 25421
      • GSK Investigational Site
  • Thueringen
    • Jena, Thueringen, Germany, 07743
      • GSK Investigational Site
• Hungary
  • Budapest, Hungary, 1106
    • GSK Investigational Site
  • Budapest, Hungary, 1125
    • GSK Investigational Site
  • Gyula, Hungary, 5700
    • GSK Investigational Site
  • Veszprém, Hungary, 8200
    • GSK Investigational Site
• Italy
  • Basilicata
    • Potenza, Basilicata, Italy, 85100
      • GSK Investigational Site
    • Rionero In Vulture (PZ), Basilicata, Italy, 85028
      • GSK Investigational Site
  • Calabria
    • Reggio Calabria, Calabria, Italy, 89125
      • GSK Investigational Site
  • Campania
    • Avellino, Campania, Italy, 83100
      • GSK Investigational Site
    • Benevento, Campania, Italy, 82100
      • GSK Investigational Site
    • Napoli, Campania, Italy, 80131
      • GSK Investigational Site
  • Liguria
    • Genova, Liguria, Italy, 16132
      • GSK Investigational Site
  • Sardegna
    • Sassari, Sardegna, Italy, 07100
      • GSK Investigational Site
  • Sicilia
    • Catania, Sicilia, Italy, 95125
      • GSK Investigational Site
  • Toscana
    • Firenze, Toscana, Italy, 50139
      • GSK Investigational Site
  • Umbria
    • Terni, Umbria, Italy, 05100
      • GSK Investigational Site
  • Veneto
    • Padova, Veneto, Italy, 35128
      • GSK Investigational Site
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 410-769
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 120-752
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 135-710
    • GSK Investigational Site
  • Songpa-gu, Seoul, Korea, Republic of, 138-736
    • GSK Investigational Site
• Russian Federation
  • Kazan, Russian Federation, 420029
    • GSK Investigational Site
  • Moscow, Russian Federation, 115478
    • GSK Investigational Site
  • Moscow, Russian Federation, 129 128
    • GSK Investigational Site
  • Moscow Region, Russian Federation, 143 423
    • GSK Investigational Site
  • Samara, Russian Federation, 443066
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 197758
    • GSK Investigational Site
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • GSK Investigational Site
  • Bratislava, Slovakia, 833 10
    • GSK Investigational Site
  • Kosice, Slovakia, 041 91
    • GSK Investigational Site
  • Poprad, Slovakia, 058 01
    • GSK Investigational Site
• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • GSK Investigational Site
  • California
    • Corona, California, United States, 92879
      • GSK Investigational Site
    • Fountain Valley, California, United States, 92708
      • GSK Investigational Site
    • Riverside, California, United States, 92501
      • GSK Investigational Site
  • Florida
    • Saint Petersburg, Florida, United States, 33705
      • GSK Investigational Site
    • Tampa, Florida, United States, 33614
      • GSK Investigational Site
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • GSK Investigational Site
    • Baton Rouge, Louisiana, United States, 70809
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21215-5271
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • GSK Investigational Site
    • Worcester, Massachusetts, United States, 01608
      • GSK Investigational Site
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • GSK Investigational Site
  • Montana
    • Great Falls, Montana, United States, 59405
      • GSK Investigational Site
  • New York
    • Bronx, New York, United States, 10467
      • GSK Investigational Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • GSK Investigational Site
  • South Carolina
    • Hilton Head Island, South Carolina, United States, 29926
      • GSK Investigational Site
    • Mount Pleasant, South Carolina, United States, 29464
      • GSK Investigational Site
    • Sumter, South Carolina, United States, 29150
      • GSK Investigational Site
  • Texas
    • Corpus Christi, Texas, United States, 78412
      • GSK Investigational Site
    • Corpus Christi, Texas, United States, 78463-3069
      • GSK Investigational Site
    • Duncanville, Texas, United States, 75137
      • GSK Investigational Site
  • Utah
    • Ogden, Utah, United States, 84403
      • GSK Investigational Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  • Total Neutrophils ≥1500/mm³ (Standard units : ≥1.5 x 10^9/L)
  • Platelets ≥100,000/mm³ (Standard units: ≥100.0 x 10^9/L)
  • Bilirubin ≤1.5 x upper limit of normal (ULN)
  • Serum Creatinine ≤1.5 mg/dL (Standard units : ≤132.6 µmol/L) OR
  • Creatinine clearance ≥60 mL/min

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:

    1. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal. For purposes of this study, postmenopausal is defined as one year without menses)
    2. child-bearing potential: must have a negative serum pregnancy test result or negative urine dipstick pregnancy test within 24 hours prior to the first dose of investigational product on Cycle 1 Day 1. Women of childbearing potential must also commit to consistent and correct use of an acceptable method of birth control. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:
• 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:

  • 5-HT3 receptor antagonists (e.g., additional ondansetron, or granisetron, dolasetron, tropisetron, ramosetron). Palonosetron is not permitted within 7 days prior to administration of study medication or investigational product;
  • benzamide / benzamide derivatives (e.g., metoclopramide, alizapride);
  • benzodiazepines (except if the subject is receiving such medication for sleep or anxiety and has been on a stable dose for at least 7 days prior to the first dose of investigational product; however, lorazepam is prohibited 24 hours prior to receiving study drug regardless of reason for use);
  • phenothiazines (e.g., prochlorperazine, promethazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine);
  • butyrophenones (e.g., haloperidol, droperidol);
  • corticosteroids within 72 hours prior to the first dose of study medication or investigational product (e.g., dexamethasone, methylprednisolone); with the exception that topical steroids for skin disorders including eye and ear drops, and inhaled steroids for respiratory disorders at ≤ 10 mg prednisone daily or its equivalent are permitted;
  • anticholinergics (e.g., scopolamine); with the exception that anticholinergics for the treatment of respiratory disorders and the management of diarrhea (e.g., ipratropium bromide, and hyoscyamine) and anticholinergic eye drops are permitted;
  • first-generation antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine; see Appendix 4); except for topical use which is permitted;
  • domperidone;
  • cannabinoids;
  • mirtazapine;
  • olanzapine.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control; Placebo + standard antiemetics	Drug: Dexamethasone; Standard antiemetics; Drug: Placebo; Placebo to match IV casopitant; Drug: Ondansetron; Standard antiemetics
EXPERIMENTAL: Single Dose IV; Casopitant + standard antiemetics	Drug: Dexamethasone; Standard antiemetics; Drug: Ondansetron; Standard antiemetics; Drug: Casopitant; Experimental NK-1 receptor antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 10, 2008
• Primary Completion (ACTUAL): April 13, 2009
• Study Completion (ACTUAL): April 13, 2009

Study Registration Dates

• First Submitted: January 15, 2008
• First Submitted That Met QC Criteria: January 24, 2008
• First Posted (ESTIMATE): January 25, 2008

Study Record Updates

• Last Update Posted (ACTUAL): January 17, 2018
• Last Update Submitted That Met QC Criteria: December 18, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: colorectal cancer; oxaliplatin; nausea; vomiting
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Dexamethasone; Ondansetron; Casopitant
• Other Study ID Numbers: NKV110721