| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chemotherapy-Induced Nausea and Vomiting (CINV) - Highly Emetogenic Chemotherapy (HEC) |
|
| 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 antiemetic dose of oral GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone for the prevention of emesis during the first 120 hours following initiation of the first cycle of highly emetogenic cisplatin-based chemotherapy. |
|
| E.2.2 | Secondary objectives of the trial |
- Determine the optimal dose of oral GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone for the prevention of nausea.
-To determine the safety and tolerability profile of oral GW679769 at various dose levels when administered in combination with ondansetron hydrochloride and dexamethasone in subjects receiving their first cycle of highly emetogenic cisplatin-based chemotherapy.
- To evaluate population pharmacokinetics and pharmacodynamics (PK/PD) of oral GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone.
- To compare the efficacy of GW679769 when administered in combination with ondansetron hydrochloride and dexamethasone to that of aprepitant administered in combination with ondansetron hydrochloride and dexamethasone.
- To compare the antiemetic efficacy and tolerability of single and repeat (3 days) dosing with GW679769 in combination with ondansetron hydrochloride and dexamethasone. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Male, or female at least 18 years of age.
2. Diagnosed with a malignant solid tumour and is scheduled to receive the first course of chemotherapy with cisplatin as a single intravenous dose of > 70 mg/m2 on study Day 1, given over a duration of between 1 and 4 hours (as per local institutional standards), either alone or in combination with other chemotherapeutic agents. Additional chemotherapeutic agents of low to high emetogenic potential (e.g. cyclophosphamide, doxorubicin, ifosfamide), must be administered after the initiation of cisplatin and be completed within 6 hours from the time that cisplatin was initiated. Chemotherapeutic agents of low emetogenic potential (e.g., gemcitabine), may be administered at the time of or after the initiation of cisplatin administration, as per usual institutional practices. Taxanes (e.g., paclitaxel, docetaxel) may be administered on study Day 1 only.
3. A Karnofsky Performance Scale score of at least 70
4. Adequate haematologic and metabolic status for receiving cisplatin chemotherapy:
- WBC > 3000/mm3.
- Platelets > 100,000/mm3.
- Serum creatinine < 1.5 mg/dL.
5. Ability and willingness to complete VASs, questionnaires and daily components of the subject diary from Day 1 until the end of the 120-hour follow-up assessment period, plus availability to respond to follow-up by study personnel at the 120-hour study period post-infusion of HEC.
6. 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 who demonstrates 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 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 or aprepitant and continuing until 30 days after the final dose of study medication or GW679769 investigational product or aprepitant.
7. Understands the nature and purpose of the study and its procedures and signs an informed consent form to indicate this understanding before any study procedures or dosing. |
|
| E.4 | Principal exclusion criteria |
1. Has previously received cytotoxic chemotherapy.
2. Is scheduled to receive greater than 1 day of cisplatin treatment during a single cycle of therapy.
3. Is scheduled to receive adjuvant chemotherapy with cyclophosphamide-containing regimens.
4. 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.
6. Has received radiation therapy to the abdomen or the pelvis in the 7 days prior to receiving the first dose of study medication or will receive radiation therapy to the abdomen or the pelvis in the 6 days following the first dose of study medication.
7. Emesis (i.e., vomiting and/or retching) experienced in the 24 hours prior to receiving the first dose of study medication.
8. Clinically significant nausea in the 24 hours prior to receiving the first dose of study medication.
9. A known central nervous system primary or metastatic malignancy, unless successfully treated with excision or radiation and has been stable for at least 1 week prior to receiving the first dose of study medication.
10. An etiology for emesis and nausea including, but not limited to, gastrointestinal obstruction, increased intracranial pressure, hypercalcaemia, active peptic ulcer.
11. Any known history of peptic ulcer disease or irritable bowel disease.
12. 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. 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.
13. Initiated systemic corticosteroid therapy at any dose within 72 hours prior to receiving the first dose of study medication except where indicated as prophylactic medication for taxane therapy(e.g., paclitaxel or docetaxel).
14. Is scheduled to receive bone marrow transplantation and/or stem cell rescue with this course of cisplatin therapy.
15. A known hypersensitivity or contraindication to ondansetron hydrochloride or ondansetron, another 5-HT3 receptor antagonist, dexamethasone, or any component of GW679769.
16. Has previously received an NK-1 receptor antagonist.
17. Has received any investigational drug within the 30 days or five half-lives (whichever is longer) prior to receiving the first dose of study medication and/or is scheduled to receive any investigational drug during the study.
18. Has received moderately and/or highly emetogenic medication within the 48 hours prior to the first dose of study medication. Opioid narcotics for cancer pain will be permitted if the subject has been on a stable dose of such medication for at least 7 days and has experienced neither emesis nor nausea from the narcotics.
19. Has taken/received palonosetron within 7 days prior to the initial dose of study medication/investigational product.
20. 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).
- Benzamide / benzamide derivatives (e.g., metoclopramide, alizapride).
- Benzodiazepines (except if the subject is receiving such medication for sleep and has been on a stable dose for at least 7 days prior to the first dose of study medication or GW679769 investigational product or aprepitant, however lorazepam is prohibited).
- 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 and inhaled steroids, and as specifically permitted elsewhere in the protocol).
- Anticholinergics (e.g., scopolamine).
- Antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine).
- Domperidone.
- Cannabinoids.
21. Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 within the following duration prior to the first administration of GW679769 investigational product or aprepitant:
Two (2) days: Clarithromycin, diltiazem, erythromycin, grapefruit juice, ketoconazole, verapamil.
Fourteen (14) days: Fluconazole, itraconazole.
22. Has taken/received inducers of CYP3A4 within 14 days prior to the first dose of study medication including carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, barbiturates, efavirenz, nevirapine, St. John’s wort and troglitazone.
23. Abnormal laboratory values in AST and/or ALT > 2.5 X the upper limit of normal without known liver metastases, > 5.0 X the upper limit of normal with liver metastases. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this clinical trial is 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 initiation of highly emetogenic cisplatin-based chemotherapy. |
|
| 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 | No |
| 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 |
|
| 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
|
|
| 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 | 7 |
| 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 | 7 |
Print
