| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chemotherapy Induced Nausea and Vomiting (CINV) 0 Moderately Emetogenic Chemotherapy (MEC) |
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
- Determine the optimal dose of oral GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone for the prevention of vomiting during the first 120 hours in subjects receiving their first cycle of moderately emetogenic chemotherapy.
- Determine the optimal dose of oral GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone for the prevention of nausea during the first 120 hours in subjects receiving their first cycle of moderately emetogenic chemotherapy.
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| E.2.2 | Secondary objectives of the trial |
- To determine the safety of oral GW679769 at various dosages when administered in combination with ondansetron hydrochloride and dexamethasone in subjects receiving their first cycle of moderately emetogenic chemotherapy.
- To quantify the impact on daily life activities of oral GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone during the first 120 hours in subjects receiving their first cycle of moderately emetogenic chemotherapy.
- To evaluate population pharmacokinetics and pharmacodynamics (PK/PD) of oral GW679769 and its active metabolites when administered in combination with ondansetron hydrochloride and dexamethasone in subjects receiving their first cycle of moderately emetogenic chemotherapy.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Male, or female not of childbearing potential (i.e., physically incapable of becoming pregnant, including postmenopausal females and those who have had attained such status via surgical means) or premenopausal women who demonstrate a negative serum or a negative urine pregnancy test within 24 hours prior to the first administration of any study medication or GW679769 investigational product and agrees to:
a) abstain from sexual intercourse for two (2) weeks prior to administration of the first dose of study medication or GW679769 investigational product until 30 days after the final dose of study medication or GW679769 investigational product, or
b) use hormonal methods of birth control (e.g., oral, injectable, or implantable) or other highly effective method of contraception [e.g., an intrauterine device (IUD)] in conjunction with a barrier method of contraception (condom, spermicidal foam, sponge, gel, diaphragm) if engaging in sexual intercourse for at least seven (7) days prior to the first dose of study medication or GW679769 investigational product and continuing until 30 days after the final dose of study medication or GW679769 investigational product.
2. At least 18 years of age.
3. Diagnosed with a malignant solid tumor, and is scheduled to receive their first course of chemotherapy as outlined below and in Section 8.1.2 ("Chemotherapeutic Regimens").
a) Chemotherapeutic regimens must not contain any therapeutic agents that are considered highly emetogenic as defined within this protocol [ see Section 14.3 “Appendix 3: Emetogenic Risk of Chemotherapy (Generic Names)”].
b) All chemotherapeutic agents will be administered according to individual institutional standards, including measures to ensure adequate hydration of the subject.
4. Karnofsky Performance Scale score of at least 70.
5. Hematologic and metabolic status must be adequate for receiving the moderately emetogenic chemotherapy regimen previously described and meet the following criteria:
• White blood cells (WBC) > 3000/mm3
• Platelets > 100,000/mm3
• Absolute neutrophil count (ANC) > 1500/mm3
• Serum creatinine < 1.5 mg/dL
• Liver enzymes must be below the following limits:
• Without known liver metastases: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 2.5 X the upper limit of normal.
• With known liver metastases: AST and/or ALT < 5.0 X the upper limit of normal.
6. Subject should be able and willing to complete daily components of the subject diary on study Day 1 and until the end of the 120 hour follow-up assessment period (beginning at the initiation of chemotherapy on study Day 1). In addition subjects should be available to respond to daily follow-up contacts by study personnel and complete a study Day 6 - 10 Visit.
7. Subject should understand the nature and purpose of this study and the study procedures and have signed an informed consent form for this study to indicate this understanding.
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| E.4 | Principal exclusion criteria |
1.Has previously received cytotoxic chemotherapy. A history of previous biological or hormonal therapy will be permitted.
2.Is scheduled to receive highly emetogenic chemotherapeutic agents as defined by this protocol
3.Is scheduled to receive adjuvant chemotherapy with cyclophosphamide-containing regimens, however neo-adjuvant cyclophosphamide-containing regimens will not be excluded
4.A female subject who is pregnant or lactating.
5.An unwillingness of the male subject to use a condom with spermicide in addition to having their female partner use another form of contraception such as an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation if the woman could become pregnant from the time of the first dose GW679769 investigational product until 84 days following administration of the final dose GW679769 investigational product.
6.Has received radiation therapy to the abdomen or the pelvis in the seven (7) days prior to receiving the first dose of study medication or GW679769 investigational product and/or will receive radiation therapy to the abdomen or the pelvis in the six (6) days following the first dose of study medication or GW679769 investigational product.
7.The subject has experienced emesis (i.e., vomiting and/or retching) or clinically significant nausea in the 24 hours prior to receiving their first dose of any study medication or GW679769 investigational product.
8.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 GW679769 investigational product
9.Has an etiology for emesis and nausea including, but not limited to, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, and/or active peptic ulcer.
10.Has been diagnosed and treated for peptic ulcer disease and who, in the investigator’s opinion, may be at risk for ulcer perforation or bleeding.
11.Has an active systemic infection or any uncontrolled disease (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.
12.Has initiated systemic corticosteroid therapy at any dose within 72 hours prior to receiving the first dose of study medication or GW679769 investigational product except where indicated as prophylactic medication for taxane therapy.
13.Is scheduled to receive bone marrow transplantation and/or stem cell rescue with this course of chemotherapy.
14.Has a known hypersensitivity or contraindication to ondansetron hydrochloride or ondansetron, another 5-HT3 receptor antagonist, dexamethasone, or any component of GW679769 or GW679769B.
15.Has previously received an NK-1 receptor antagonist, with the exception of GW679769 previously administered in prior study cycles for those subjects continuing study participation beyond Cycle 1.
16.Has received an investigational drug in the previous 30 days or who is scheduled to receive any investigational drug in addition to GW679769 during the study period with the exception of GW679769 previously administered in prior study cycles for those subjects continuing study participation beyond Cycle 1.
17.Has taken/received any medication of moderate or high emetogenic potential within the 48 hours prior to the first dose of study medication or GW679769 investigational product. Opioid narcotics for cancer pain will be permitted if the subject has been on a stable dose of such medication for at least seven (7) days and has experienced neither emesis nor nausea from the narcotics.
18.Has taken/received any medication with known or potential antiemetic activity within the 24-hour period prior to receiving study drug, unless otherwise stated in protocol as acceptable.
19.Has taken/received palonosetron within 7 days prior to initial dose of study medication or GW679769 investigational product.
20.Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 within the following duration prior to administration of GW679769 investigational product:
•Two (2) days: Clarithromycin, diltiazem, erythromycin, grapefruit juice, ketoconazole, verapamil
•Fourteen (14) days:Fluconazole, itraconazole.
21.Has taken/received inducers of CYP3A4 and CYP3A5 within fourteen (14) days prior to the administration of GW679769 investigational product, including carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort, and troglitazone.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
- The proportion of subjects who achieve a complete response (defined as no vomiting, no retching, no rescue therapy, and no premature discontinuation from the study) for each treatment arm during the 120 hour evaluation period following the initiation of moderately emetogenic chemotherapy.
- The proportion of subjects experiencing significant nausea during the 120 hour evaluation period following the initiation of the first cycle of moderately emetogenic chemotherapy, as assessed by a Visual Analogue Scale (VAS).
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
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