The Effects Of GW679769 (Casopitant) On The Pharmacokinetics Of Docetaxel In Subjects With Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00440128
First received: February 22, 2007
Last updated: March 15, 2012
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Nausea and Vomiting, Chemotherapy-Induced
Cancer
Drug: Docetaxel
Drug: Casopitant/Docetaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Randomized, Two Period Crossover Study to Investigate the Effects of GW679769 on the Pharmacokinetics of Docetaxel in Subjects With Cancer

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Plasma levels of study drugs will be taken on Day 1 & 8. [ Time Frame: taken on Day 1 & 8. ] [ Designated as safety issue: Yes ]
    Plasma samples of study drugs


Secondary Outcome Measures:
  • Safety is evaluated by: -AEs monitored at each visit [ Time Frame: starting at Day 1. ] [ Designated as safety issue: Yes ]
  • -Physical exam, vital signs, & ECOG performance status score [ Time Frame: at Screening, Day 1,8,&15. ] [ Designated as safety issue: Yes ]
  • -ECG [ Time Frame: at Screening & Day 15. ] [ Designated as safety issue: Yes ]
  • -Serum Pepsinogen levels monitored [ Time Frame: at Screening & Followup ] [ Designated as safety issue: Yes ]
  • Terminal half-life (t1/2, as data permit), AUC(0-t), volume of distribution at steady state (Vdss), and clearance (Cl) of docetaxel [ Time Frame: on Day 1 and 8. ] [ Designated as safety issue: Yes ]
  • Lowest measured absolute neutrophil count. [ Time Frame: on Day 1 and 8 ] [ Designated as safety issue: Yes ]
  • Physical exam findings, blood pressure, heart rate, clinical laboratory tests, clinical monitoring/observation, and adverse events reporting. [ Time Frame: on Day 1 and 8 ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: May 2007
Study Completion Date: July 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Docetaxel
Docetaxel
Drug: Docetaxel
Docetaxel
Other Name: Docetaxel
Experimental: Docetaxel/Casopitant
Docetaxel/Casopitant
Drug: Casopitant/Docetaxel
Casopitant/Docetaxel
Other Names:
  • Docetaxel
  • Casopitant

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 Exclusion Criteria 5) within 14 days prior to the first dose of study medication
  • Use of drugs with a narrow therapeutic index that interact with the P-glycoprotein pathway within 14 days prior to the first dose of study medication until 14 days after the last dose of docetaxel including digoxin.
  • Use of drugs with a narrow therapeutic index that are metabolized by CYP2C8 within 14 days prior to the first dose of study medication including repaglinide and torsemide.
  • Disease that will significantly affect absorption of oral medications.
  • Inadequate venous access for pharmacokinetic sampling.
  • Unresolved Grade 2 or worse toxicity from prior therapy.
  • Active peptic ulcer disease (PUD) or a history of PUD of unknown etiology. NOTE: Subject is eligible to enter and participate in this study if they have a history of PUD of known etiology with documentation from a gastroenterologist or other qualified physician of the etiology of the PUD and that effective treatment was provided with full eradication of ulcers and symptoms. Subjects who present with symptoms of gastroesophageal reflux disease (GERD) are eligible. However, if the investigator suspects PUD in such a subject, the subject must have a GI assessment to rule out PUD. If assessment is negative, subject may enter the study. For these subjects, appropriate steps must also have been taken to minimize the risk of reoccurrence. If PUD was non-steroidal anti-inflammatory drug (NSAID) induced, the subject should no longer be taking NSAID medication(s). If PUD was induced by H. pylori, the subject should have been appropriately treated.
  • Stool positive for occult blood. Test may be repeated once if subject did not abstain from red meat for the previous three days.
  • Pepsinogen level below the lower limit of laboratory reference range (LLRR).
  • Troponin level above 10% of the coefficient of variation of the assay as determined by the laboratory performing the test.
  • Calculated QT interval (QTc) > 480 msecs.
  • Clinically significant cardiac disease that would interfere with participation in the study as determined by the investigator.
  • Known or suspected iron deficiency.
  • Use of NSAIDS, including aspirin at any dose, and including COX2 inhibitors. These medications are prohibited 7 days prior to administration of study drug and for the duration of the study until 72 hours after the last dose of study drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00440128

Locations
United States, Arkansas
GSK Investigational Site
Hot Springs, Arkansas, United States, 71913
United States, Iowa
GSK Investigational Site
Iowa City, Iowa, United States, 52242
United States, Michigan
GSK Investigational Site
Detroit, Michigan, United States, 48201
United States, New Hampshire
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00440128     History of Changes
Other Study ID Numbers: NKV100781
Study First Received: February 22, 2007
Last Updated: March 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Casopitant,
Neurokinin-1 Receptor Antagonist,
NK-1 Receptor Antagonist,
Drug-Interaction,
CYP3A
GW679769,
Docetaxel,

Additional relevant MeSH terms:
Docetaxel
Casopitant
Neurokinin-1 Receptor Antagonists
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 15, 2014