Nausea and Vomiting, Chemotherapy-Induced
Conditions
Keywords
Casopitant,, Neurokinin-1 Receptor Antagonist,, Drug-Interaction,, CYP3A, NK-1 Receptor Antagonist,, GW679769,, Docetaxel,
Brief summary
The purpose of the study is to evaluate the effect of the study drug (GW679769) on a commonly used chemotherapy drug (docetaxel) which will be given I.V. Blood samples will be taken to see if the GW679769 alters the blood levels of the chemotherapy. The study will last about 2 weeks with a final follow-up visit 6 weeks later.
Interventions
DRUGDocetaxel
Docetaxel
DRUGCasopitant/Docetaxel
Casopitant/Docetaxel
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female * 18 years of age * A female is eligible to enter and participate in this study if she is of: 1. Non-child-bearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had at least one of the following: * Has had a hysterectomy, or * Has had a bilateral oophorectomy (ovariectomy), or * Has had a bilateral tubal ligation, or • Is considered post-menopausal (defined as amenorrheic for ≥ 1 year) and having serum follicle stimulating hormone (FSH) and serum estradiol concentrations consistent with post-menopausal status. 2. Childbearing potential, has a negative serum pregnancy or negative urine pregnancy test within 24 hours prior to administration of the first dose of study medication and agrees to one of the following: * Complete abstinence from sexual intercourse from two weeks prior to administration of the first dose of investigational product until 30 days after the final dose of study medication. * Use double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm) from two weeks prior to administration of the first dose of investigational product until 30 days after the final dose of study medication. * Vasectomized partner who has been documented to be sterile prior to the female subject's entry and is the sole sexual partner for that female. * NOTE: if women of childbearing potential are enrolled, they must use double-barrier contraception in addition to oral contraceptives during the active study treatment period until 6 weeks after the final dose of study medication. * Histologically confirmed malignant solid tumor and is scheduled to receive at least 2 courses of chemotherapy with docetaxel as a single intravenous dose of 20 to 40 mg/m2 given over a duration of one hour and repeated weekly. * Received eight or fewer previous doses of docetaxel. Subjects that have received more than eight doses of docetaxel must receive permission from the GSK medical monitor in order to be eligible for the study. * ECOG performance status score of less than or equal to 2 NOTE: If the subject's performance status deteriorates between the screening Visit and the time of first dose of study drug to a score \> 2, the subject will be excluded from the study * Adequate hematologic and other physiological organ function as evidenced by Absolute Neutrophil Count ≥1500/mm3. Platelets ≥ 100,000/mm3 Hemoglobin ≥ 9 g/dL Serum creatinine \< 1.5 mg/dL Total Bilirubin ≤ upper limit of the reference range Aspartate Transaminase (AST) \< 2 x upper limit of the reference range Alanine Transaminase (ALT) \< 2 x upper limit of the reference range Alkaline Phosphatase \< 2.5 x upper limit of the reference range. Calculated creatinine clearance \> 50 mL/min (measured by Cockcroft Gault Formula;) * Written informed consent is obtained prior to any study-specific procedures or assessments. * Able to swallow and retain oral medications.
Exclusion criteria
* Pregnant or lactating. * Received radiation therapy to the abdomen or the pelvis in the 28 days prior to receiving the first dose of study medication or that are scheduled to receive radiation therapy to the abdomen or the pelvis in the six days following the first dose of study medication. * Received a dose of docetaxel during the week prior to Day -1. * Known central nervous system primary or metastatic malignancy, unless successfully treated with excision or radiation and has been stable for at least 3 months prior to receiving the first dose of study medication. * Active systemic infection or any poorly controlled medical condition (other than malignancy) which, in the opinion of the investigator, may confound the results of the study or pose an unwarranted risk to the subject. Subjects with a previous, but not current, history of alcoholism may be permitted provided that, in the investigator's opinion, the subject's disease state will not confound the results of the study. * Receiving regular treatment with high dose systemic corticosteroid therapy or steroid dose within 72 hours prior to receiving the first dose of study medication. Topical steroids and inhaled corticosteroids with a steroid dose of less than or equal to 10 mg prednisone daily (or its equivalent) are permitted if the subject has been on this dose for at least 14 days prior to dosing. * Hypersensitivity or contraindication to ondansetron or other 5-HT3 receptor antagonist, dexamethasone, docetaxel, casopitant, or any component of the above mentioned medications. * Received an investigational drug within the 28 days or five half-lives (whichever is longer) prior to receiving the first dose of study medication, or is scheduled to receive any investigational drug during the study. * Use of strong inhibitors of CYP3A4 or CYP3A5 prior to the first dose of study medication * Use of inducers of CYP3A4 or CYP3A5 (other than steroids described in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma levels of study drugs will be taken on Day 1 & 8. | taken on Day 1 & 8. | Plasma samples of study drugs |
Secondary
| Measure | Time frame |
|---|---|
| -Physical exam, vital signs, & ECOG performance status score | at Screening, Day 1,8,&15. |
| -ECG | at Screening & Day 15. |
| -Serum Pepsinogen levels monitored | at Screening & Followup |
| Safety is evaluated by: -AEs monitored at each visit | starting at Day 1. |
| Lowest measured absolute neutrophil count. | on Day 1 and 8 |
| Physical exam findings, blood pressure, heart rate, clinical laboratory tests, clinical monitoring/observation, and adverse events reporting. | on Day 1 and 8 |
| Terminal half-life (t1/2, as data permit), AUC(0-t), volume of distribution at steady state (Vdss), and clearance (Cl) of docetaxel | on Day 1 and 8. |
Countries
United States
Outcome results
None listed