E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post Operative Nausea and Vomiting (PONV) Post Discharge Nausea and Vomiting (PDNV) |
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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 |
The primary objective of this clinical trial is to determine the optimal single dose of oral GW679769 when administered in combination with intravenous (IV) ondansetron hydrochloride for the prevention of emesis (defined as vomiting or retching) during the first 24 hours following the emergence from anesthesia in female subjects with known risk factors for post-operative nausea and vomiting (PONV) who are undergoing surgical procedures that are associated with an increased emetogenic risk. |
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E.2.2 | Secondary objectives of the trial |
1.Determine the optimal single dose of oral GW679769 when administered in combination with intravenous ondansetron. 2.Determine the optimal single dose of oral GW679769 when administered in combination with intravenous ondansetron hydrochloride. 3.Determine the safety of oral GW679769 at various dose levels. 4.Quantify the impact on daily life activities, as assessed by a Functional Living Index - Emesis (FLIE) questionnaire. 5.Assess the subject satisfaction with the control of PONV and post-discharge nausea and vomiting (PDNV). 6.Evaluate the reporting of pain experienced by subjects during the 2, 6, and 24 hour evaluation periods, and each subsequent 24 hour evaluation period (up to 120 hours). 7.Evaluate population pharmacokinetics (PK) and pharmacodynamics (PD) of a single dose of oral GW679769. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Is a female with the following three (3) risk factors: •Pre-menopausal or peri-menopausal between the ages of 18-55 years, who is not of childbearing potential (i.e., physically incapable of becoming pregnant) or who demonstrates a negative serum or a negative urine pregnancy test within 24 hours prior to the first administration of study medication and agrees to: a)abstain from sexual intercourse for two (2) weeks prior to administration of the first dose of study medication until 30 days after the final dose of study medication, 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 and continuing until 30 days after the final dose of study medication. •Has never smoked or used (e.g., chewing) tobacco, or has successfully quit smoking and/or using tobacco and has been a nonsmoker and nonuser (including a nicotine patch) for at least the previous twelve (12) consecutive months. •Known to have a history of: apost-operative nausea and vomiting, and/or bmotion sickness. 2.Is undergoing a laparoscopic/laparotomic gynecological surgical procedure or laparoscopic cholecystectomy that is scheduled for no less than one (1) hour in duration and no longer than three (3) hours in duration. 3.Is scheduled to receive general anesthesia with an anesthetic regimen as described in Section 4.2. 4.Meets the American Society of Anesthesiologists (ASA) Physical Status Classification of I or II preoperatively on the day of surgery (see Section 14.5.). 5.Has hematology and blood chemistry values within acceptable limits [i.e., within 10% outside (either above or below) normal reference values, unless otherwise specified] for surgery 6.Is able and willing to complete daily components of the subject diary preoperatively on the day of surgery and until the end of the 120 Hour Follow-up Assessment period, and will be available to respond to follow-up by study personnel at the 120 hour study period post-emergence from anesthesia. 7.Understands the nature and purpose of this study and the study procedures and has signed an informed consent form (ICF) for this study to indicate this understanding. |
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E.4 | Principal exclusion criteria |
1.Meets ASA Physical Status Classification of III, IV, or V preoperatively on the day of surgery (see Section 14.5.). 2.Is pregnant or lactating. 3.Is post-menopausal. If the last menstrual period was within the previous eighteen (18) months, a follicle stimulating hormone (FSH) evaluation must be elevated into the postmenopausal range. 4.Is scheduled to undergo a laparoscopic biopsy. 5.Is scheduled to receive neuroaxial anesthesia or total intravenous volatile anesthesia (TIVA). 6.Is scheduled to receive propofol for maintenance of anesthesia. 7.Is scheduled to have gastric contents suctioned continuously during the surgical procedure via a nasogastric (NG) tube, or a nasogastric or oral gastric tube during the post-operative period. 8.Has been taking more than 10 - 15 mg of oxycodone, or an equivalent opioid dose. 9.Has received an investigational drug in the previous thirty (30) days or who is scheduled to receive any investigational drug in addition to GW679769 during the study period. 10.Has persistant or recurrent nausea and/or vomiting due to other etiologies. 11.Has experienced retching or vomiting or uncontrolled nausea within 48 hours prior to administration of study drug. 12.Has experienced significant nausea in the 24 hour period prior to receiving the dose of GW679769 study medication. 13.Has received radiation therapy to the abdomen or the pelvis in the seven days prior to receiving study medication and/or will receive radiation therapy to the abdomen or the pelvis in the evaluation period. 14.Has a history of wound dehiscence. 15.Has a history of previous or current peptic ulceration or inflammatory bowel disease. 16.Has a history of any other illness, that, in the opinion of the investigator, may pose an unacceptable risk by administering study medication. 17.Has any current or past medical condition (e.g., vagotomy) and/or require medication to treat a condition that could confound the evaluation of the data collected in this clinical trial. 18.Has a known hypersensitivity or contraindication to ondansetron hydrochloride or ondansetron, another 5-HT3 receptor antagonist, any scheduled anesthetic or analgesic agents, or any component of GW679769. 19.Has a known hypersensitivity to fentanyl and/or ketorolac tromethamine. 20.Has a known allergy to eggs or egg products. 21.Is scheduled to receive antiemetics not outlined in the study dosing scheme. 22.Has received medication with known or potential antiemetic activity within the 24 hour period prior to receiving study drug. 23.Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 within the following duration prior to administration of the study medication 24.Has taken/received inducers of CYP3A4 and CYP3A5 within fourteen (14) days prior to the administration of the study medication. 25.Has previously received an NK-1 receptor antagonist. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the number of subjects who achieve a complete response (defined as no vomiting, no retching, no rescue therapy, and no premature discontinuation from the study) during the first 24 hour evaluation period following the emergence from anesthesia. |
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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 | Information not present in EudraCT |
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 | 6 |
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 | 6 |