E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cisplatin-induced nausea and vomiting |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054133 |
E.1.2 | Term | Prophylaxis of nausea and vomiting |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
To determine the lowest dose of APD421 which shows an adequate level of effectiveness at preventing sickness in patients given cisplatin chemotherapy (compared to what would be expected based on historical data on other known anti-emetics). |
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E.2.2 | Secondary objectives of the trial |
To quantify the severity and timescale of any sickness seen in patients given APD421 (at various doses) before cisplatin chemotherapy, and to assess the safety of APD421 at various doses. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients ≥ 18 years of age. 2. Ability and willingness to give written informed consent. 3. Patients scheduled to receive, on day 1 of their chemotherapy, a first cisplatin chemotherapy infusion at a dose of 50 mg/m2 or greater. 4. Karnofsky performance score ≥ 60%. 5. Adequate cardiac, hepatic and renal function • QTc interval < 500 ms • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 5 x upper limit normal (ULN) • Bilirubin < 3 x ULN • Creatinine < 2 x ULN. 6. Adequate haematological function • Haemoglobin ≥ 9 g/dL • White blood count ≥ 3.0 x 109/L • Platelet count ≥ 100 x 109/L 7. For females of child-bearing potential: ability and willingness to use a highly effective form of contraception (e.g., abstinence from sexual intercourse, surgical sterilisation (of subject or partner) or a double-barrier method of contraception such as either an intra-uterine device (IUD) or an occlusive cap with spermicide, in conjunction with partner’s use of a condom) during the study and for a period of at least 48 hours afterwards. |
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E.4 | Principal exclusion criteria |
1. Patients scheduled to receive, prior to or in the 24 hours after cisplatin, any chemotherapeutic agent with a high or moderate emetic risk according to published criteria. 2. Patients scheduled to receive paclitaxel or docetaxel. 3. Patients undergoing abdominal or pelvic irradiation within 48 hours prior to screening or scheduled to receive abdominal or pelvic irradiation between screening and 24 hours after cisplatin administration. 4. Patients receiving amisulpride for any indication within the last 2 weeks. 5. Patients who are allergic to amisulpride or any of the excipients of APD421. 6. Patients with a pre-existing vestibular disorder. 7. Patients being treated with regular anti-emetic therapy including corticosteroids. 8. Patients receiving inhaled corticosteroids, unless started more than one month prior to the expected date of study entry. 9. Patients being treated with medications which could induce torsades de pointes, including Class Ia antiarrhythmic agents such as quinidine, disopyramide, procainamide; Class III antiarrhythmic agents such as amiodarone and sotalol; and other medications such as bepridil, cisapride, thioridazine, methadone, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin. 10. Patients being treated with levodopa. 11. Patients receiving benzodiazepines, unless on a stable dose for at least one month prior to the expected date of study entry. 12. Patients with pre-existing nausea or vomiting in the 24 hours before receiving cisplatin chemotherapy, e.g. anticipatory emesis. 13. Patients who are pregnant or breast feeding. 14. Patients with a history of alcohol abuse. 15. Patients with pre-existing, clinically significant cardiac arrhythmia. 16. Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study. 17. Patients who have participated in another study within the previous 28 days. 18. Patients who are allergic to ondansetron or who would otherwise be considered inappropriate to receive ondansetron. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is complete response, described as an absence of emetic episodes and no rescue medication use in the 24-hour period after the start of the cisplatin infusion. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |