Intravenous And Oral Casopitant (GW679769) For The Prevention Of Chemotherapy Induced Nausea And Vomiting

NCT ID: NCT00366834

Last Updated: 2012-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1840 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-07-31

Study Completion Date

2009-10-31

Brief Summary

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This is a Phase III trial designed to demonstrate that casopitant (GW679769) plus dexamethasone and ondansetron is more effective in the prevention of vomiting than dexamethasone and ondansetron alone following the administration of moderately emetogenic chemotherapy.

Detailed Description

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A Phase III, Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group Study of the Safety and Efficacy of the Intravenous and Oral Formulations of the Neurokinin-1 Receptor Antagonist, Casopitant (GW679769) in Combination with Ondansetron and Dexamethasone for the Prevention of Nausea and Vomiting Induced by Moderately Emetogenic Chemotherapy

Conditions

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Vomiting Nausea Nausea and Vomiting, Chemotherapy-Induced

Keywords

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Anthracycline Cyclophosphamide Moderately Nausea Emetogenic Vomiting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Control

ondansetron 8 mg oral twice daily on Day 1-3 and dexamethasone 8 mg IV on Day 1 + placebo

Group Type PLACEBO_COMPARATOR

Dexamethasone intravenous

Intervention Type DRUG

Ondansetron oral tablets

Intervention Type DRUG

placebo

Intervention Type DRUG

casopitant placebo

Single dose oral

ondansetron 8 mg oral twice daily on Day 1-3 and dexamethasone 8 mg IV + casopitant 150 mg on Day 1

Group Type EXPERIMENTAL

Casopitant (GW679769) oral tablets

Intervention Type DRUG

Dexamethasone intravenous

Intervention Type DRUG

Ondansetron oral tablets

Intervention Type DRUG

3-day oral

ondansetron 8 mg oral twice daily on Day 1-3 and dexamethasone 8 mg IV + casopitant 150 mg on Day 1 + 50 mg on days 2 \& 3

Group Type EXPERIMENTAL

Casopitant (GW679769) oral tablets

Intervention Type DRUG

Dexamethasone intravenous

Intervention Type DRUG

Ondansetron oral tablets

Intervention Type DRUG

3-day IV/oral

ondansetron 8 mg oral twice daily on Day 1-3 and dexamethasone 8 mg IV on Day 1 + 90 mg IV casopitant on day 1 and 50 mg oral casopitant on days 2 \& 3

Group Type EXPERIMENTAL

Casopitant (GW679769) oral tablets

Intervention Type DRUG

Casopitant (GW679769) intravenous

Intervention Type DRUG

Dexamethasone intravenous

Intervention Type DRUG

Ondansetron oral tablets

Intervention Type DRUG

Interventions

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Casopitant (GW679769) oral tablets

Intervention Type DRUG

Casopitant (GW679769) intravenous

Intervention Type DRUG

Dexamethasone intravenous

Intervention Type DRUG

Ondansetron oral tablets

Intervention Type DRUG

placebo

casopitant placebo

Intervention Type DRUG

Other Intervention Names

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Dexamethasone intravenous Casopitant (GW679769) oral tablets Casopitant (GW679769) intravenous

Eligibility Criteria

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Inclusion Criteria

* A subject will be considered eligible for inclusion in this 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 their first course of an anthracycline and cyclophosphamide containing moderately emetogenic chemotherapy regimen for the treatment of a solid malignant tumor as outlined in Section 8.1.1.
* Has an ECOG performance status of 0, 1, or 2.
* Hematologic and metabolic status must be adequate for receiving a moderately emetogenic regimen and meet 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 ULN
* Liver enzymes must be below the following limits:

* Without known liver metastases: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal.
* With known liver metastases: AST and/or ALT ≤ 5.0 x upper limit of normal.
* Is willing and able to complete daily components of the subject diary for each study cycle.
* Women of childbearing potential; must 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 a physician, are as follows:

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 of Cycle 1, Day 1 and agrees to one of the following:

* 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 potential drug interaction (minimum of six weeks)
* double-barrier method of contraception consisting of spermicide with either condom or diaphragm
* intra-uterine device (IUD) 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 three days),
* if subjects indicate 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

* Has previously received cytotoxic chemotherapy. A history of previous biological or hormonal therapy will be permitted.
* Is a female subject who is pregnant or lactating.
* Has received radiation therapy to the brain, abdomen, or pelvis in the ten days prior to the first dose of study medication or casopitant investigational product and/or will receive radiation therapy to the brain, abdomen, or the pelvis in the six days following the first dose of study medication (ZOFRAN and dexamethasone) or casopitant investigational product.
* Is scheduled to receive taxane therapy during cycle 1. Note that subjects will be permitted to receive taxane therapy in conjunction with one of the allowed MEC regimens during subsequent cycles.
* 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 casopitant investigational product.
* Has a known central nervous system primary or metastatic malignancy, unless successfully treated with excision or radiation and has been medically stable for at least 1 week prior to receiving the first dose of study medication or casopitant investigational product.
* Has history of documented peptic ulcer disease (via endoscopy or x-ray), active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, 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 ZOFRAN, another 5-HT3 receptor antagonist, dexamethasone, or any component of casopitant.
* Has previously received an NK-1 receptor antagonist.
* Received an investigational drug in the previous 30 days or is scheduled to receive any investigational drug other than casopitant during the study period.
* Has taken/received any medication of moderate or high emetogenic potential within the 48 hours prior to the first dose of study medication or casopitant investigational product. Opioid narcotics for cancer pain will be permitted if the subject has been on a stable dose 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 prior to receiving study drug. This includes, but is not limited to:

* 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron). Palonestron is not permitted within 7 days prior to administration of 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 seven days prior to the first dose of casopitant 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)
* butyrophenone (e.g., haloperidol, droperidol)
* corticosteroids (e.g., dexamethasone, methylprednisolone; with the exception of topical steroids for skin disorders, inhaled steroids for respiratory disorders, and prophylactic treatment for taxane therapy during subsequent cycles)
* anticholinergics (e.g., scopolamine, with the exception of inhaled anticholingerics for respiratory disorders e.g., ipratropium bromide)
* antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine), except for prophylactic use for taxane therapy during cycle 2-4
* domperidone
* cannabinoids
* mirtazpine
* olanzapine
* Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 for a specified period prior to administration of casopitant investigational product (see Section 8.2.1 "Inhibitors of CYP3A4 and CYP3A5")
* Has taken/received inducers of CYP3A4 and CYP3A5 within fourteen days prior to the administration of casopitant investigational product. (see Section 8.2.2 "Inducers of CYP3A4 and CYP3A5")
* Is taking the anti-diabetic agent repaglinide or the diuretic torsemide. Investigators are advised to exercise caution if including patients taking the anti-diabetic agents rosiglitazone or pioglitazone, or antimalarial agents such as chloroquine and amodiaquine, as the metabolite of casopitant is a potential inhibitor of CYP2C8 (See Section 8.2.3 "Substrates for CYP2C8" and Section 8.4 "Necessary Caution with CYP2C8 Substrates").
* Is currently taking or plans to take the any of the following CYP3A4 substrates: astemizole, cisapride, pimozide, terfenadine.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Glendale, Arizona, United States

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Fayetteville, Arkansas, United States

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Hot Springs, Arkansas, United States

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Jonesboro, Arkansas, United States

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Concord, California, United States

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Fountain Valley, California, United States

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Fresno, California, United States

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Greenbrae, California, United States

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La Verne, California, United States

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Los Angeles, California, United States

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Orange, California, United States

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Poway, California, United States

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San Diego, California, United States

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Soquel, California, United States

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Norwich, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Boynton Beach, Florida, United States

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Brooksville, Florida, United States

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Fort Lauderdale, Florida, United States

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Fort Lauderdale, Florida, United States

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Inverness, Florida, United States

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Miami, Florida, United States

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New Port Richey, Florida, United States

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Tamarac, Florida, United States

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Tampa, Florida, United States

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West Palm Beach, Florida, United States

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Augusta, Georgia, United States

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Columbus, Georgia, United States

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Lawrenceville, Georgia, United States

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Centralia, Illinois, United States

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Galesburg, Illinois, United States

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Skokie, Illinois, United States

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Evansville, Indiana, United States

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Muncie, Indiana, United States

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Terre Haute, Indiana, United States

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Mason City, Iowa, United States

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Hazard, Kentucky, United States

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Lexington, Kentucky, United States

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Alexandria, Louisiana, United States

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Baton Rouge, Louisiana, United States

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Metairie, Louisiana, United States

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Baltimore, Maryland, United States

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Baltimore, Maryland, United States

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Pittsfield, Massachusetts, United States

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Worcester, Massachusetts, United States

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Clinton Township, Michigan, United States

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Free Soil, Michigan, United States

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Saint Joseph, Michigan, United States

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Troy, Michigan, United States

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Hattiesburg, Mississippi, United States

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Tupelo, Mississippi, United States

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Jefferson City, Missouri, United States

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Rolla, Missouri, United States

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St Louis, Missouri, United States

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Billings, Montana, United States

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Great Falls, Montana, United States

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Denville, New Jersey, United States

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Newark, New Jersey, United States

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Somerville, New Jersey, United States

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Sparta, New Jersey, United States

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Albuquerque, New Mexico, United States

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Buffalo, New York, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Bismarck, North Dakota, United States

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Akron, Ohio, United States

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Bethlehem, Pennsylvania, United States

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Hershey, Pennsylvania, United States

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Sayre, Pennsylvania, United States

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Mt. Pleasant, South Carolina, United States

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Sumter, South Carolina, United States

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Corpus Christi, Texas, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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Richardson, Texas, United States

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Logan, Utah, United States

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Ogden, Utah, United States

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Burlington, Vermont, United States

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Everett, Washington, United States

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Spokane, Washington, United States

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Tacoma, Washington, United States

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Huntington, West Virginia, United States

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Huntington, West Virginia, United States

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Madison, Wisconsin, United States

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Capital Federal, Buenos Aires, Argentina

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Mendoza, Mendoza Province, Argentina

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Rosario, Santa Fe Province, Argentina

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San Miguel de Tucumán, Tucumán Province, Argentina

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Quilmes, , Argentina

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Salzburg, , Austria

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Sankt Pölten, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Vöcklabruck, , Austria

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Brussels, , Belgium

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Ghent, , Belgium

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Ottignies, , Belgium

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Plovdiv, , Bulgaria

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Shumen, , Bulgaria

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Sofia, , Bulgaria

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Vancouver, British Columbia, Canada

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Moncton, New Brunswick, Canada

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St. John's, Newfoundland and Labrador, Canada

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Oshawa, Ontario, Canada

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Thunder Bay, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Windsor, Ontario, Canada

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Charlottetown, Prince Edward Island, Canada

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Greenfield Park, Quebec, Canada

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Laval, Quebec, Canada

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Lévis, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Saskatoon, Saskatchewan, Canada

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Zagreb, , Croatia

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Brno, , Czechia

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Chomutov, , Czechia

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Ostrava - Poruba, , Czechia

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Pardubice, , Czechia

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Prague, , Czechia

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Tábor, , Czechia

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Ústí nad Labem, , Czechia

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Herlev, , Denmark

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Hilleroed, , Denmark

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Tallinn, , Estonia

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Tartu, , Estonia

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Heidelberg, Baden-Wurttemberg, Germany

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Ingolstadt, Bavaria, Germany

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Munich, Bavaria, Germany

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Munich, Bavaria, Germany

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Würzburg, Bavaria, Germany

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Hamburg, City state of Hamburg, Germany

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Hamburg, City state of Hamburg, Germany

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Hamburg, City state of Hamburg, Germany

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Kassel, Hesse, Germany

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Würselen, North Rhine-Westphalia, Germany

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Berlin, State of Berlin, Germany

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Berlin, State of Berlin, Germany

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Bad Berka, Thuringia, Germany

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Jena, Thuringia, Germany

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Athens, , Greece

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Athens, , Greece

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Kavala, , Greece

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Pátrai, , Greece

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Thessaloniki, , Greece

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Hong Kong, , Hong Kong

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Shatin, , Hong Kong

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Tuenmen, , Hong Kong

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Wan Chai, , Hong Kong

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Győr, , Hungary

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Gyula, , Hungary

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Veszprém, , Hungary

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Pune, , India

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Dublin, , Ireland

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Dublin, , Ireland

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Dublin, , Ireland

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Tallaght, Dublin, , Ireland

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Wilton, Cork, , Ireland

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Benevento, Campania, Italy

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Rome, Lazio, Italy

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Genoa, Liguria, Italy

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Sanremo (IM), Liguria, Italy

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Sassari, Sardinia, Italy

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Perugia, Umbria, Italy

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Liepāja, , Latvia

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Riga, , Latvia

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Riga, , Latvia

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Kaunas, , Lithuania

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Klaipėda, , Lithuania

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Vilnius, , Lithuania

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Durango, Durango, Mexico

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Mérida, Yucatán, Mexico

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Lahore, , Pakistan

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Lima, Lima Province, Peru

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Lima, Lima Province, Peru

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Callao, , Peru

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Cebu, , Philippines

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Manila, , Philippines

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Quezon City, , Philippines

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Santa Cruz, Manila, , Philippines

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Krakow, , Poland

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow Region, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Yaroslavl, , Russia

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Bratislava, , Slovakia

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Bratislava, , Slovakia

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Nitra, , Slovakia

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Poprad, , Slovakia

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Žilina, , Slovakia

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Athlone Park, Amanzimtoti, , South Africa

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Bloemfontein, , South Africa

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Observatory, , South Africa

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Panorama, , South Africa

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Parktown, , South Africa

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Saxonwold, Johannesburg, , South Africa

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Seoul, , South Korea

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Seoul, , South Korea

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Donostia / San Sebastian, , Spain

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Madrid, , Spain

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Ourense, , Spain

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Santiago de Compostela, , Spain

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Segovia, , Spain

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Zamora, , Spain

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Kaohsiung City, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Chelmsford, Essex, United Kingdom

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Aberdeen, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Maidstone, , United Kingdom

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Nottingham, , United Kingdom

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Shrewsbury, , United Kingdom

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Countries

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Brazil United States Argentina Austria Belgium Bulgaria Canada Croatia Czechia Denmark Estonia Germany Greece Hong Kong Hungary India Ireland Italy Latvia Lithuania Mexico Pakistan Peru Philippines Poland Russia Slovakia South Africa South Korea Spain Taiwan Thailand United Kingdom

References

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Herrstedt J, Apornwirat W, Shaharyar A, Aziz Z, Roila F, Van Belle S, Russo MW, Levin J, Ranganathan S, Guckert M, Grunberg SM. Phase III trial of casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy. J Clin Oncol. 2009 Nov 10;27(32):5363-9. doi: 10.1200/JCO.2009.21.8511. Epub 2009 Oct 5.

Reference Type RESULT
PMID: 19805683 (View on PubMed)

Other Identifiers

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NKV102549

Identifier Type: -

Identifier Source: org_study_id