E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10028817 |
E.1.2 | Term | Nausea and vomiting symptoms |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014542 |
E.1.2 | Term | Emesis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028813 |
E.1.2 | Term | Nausea |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
The primary objective is to compare whether the administration of the neurokinin1-receptor antagonist (NK1-RA) fosaprepitant dimeglumine results in a significant improvement in nausea scores from baseline to 24 hours as compared with placebo. In patients included because of vomiting only (nausea score less than moderate), the primary parameter will be change in number of emetic episodes from baseline to 24 hours. |
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E.2.2 | Secondary objectives of the trial |
1. Two-item nausea score and CAT (computer adaptive testing)-score recorded on the ext. EORTC QLQ-C15-PAL at baseline, 24 hours and after 7 days. 2. Number of emetic episodes (vomit/dry retch) in the first 24 hours after administration of study medication. 3. Time to first emetic episode. 4. Nausea score measured daily for 7 days following administration of study medication 5. Number of emetic episodes measured daily for 7 days following the administration of study medication. 6. Tolerability. 7. Parameters indicative of efficacy: appetite, fatigue, pain, emotional function and overall quality of life. 8. Use of rescue anti-emetics.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Advanced cancer 2. Age ≥ 18 years 3. One or both of the following: 3.1. Nausea at least ‘moderate’ on the baseline diary 3.2. At least 1 emetic episode within the last 24 hours (recorded on the baseline diary) 4. Ability to read and understand the forms required for the study. 5. Life-expectancy more than 2 weeks.
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E.4 | Principal exclusion criteria |
1. Contraindications for fosaprepitant including allergic reaction. 2. ALAT > 5 times above normal 3. Symptoms of increased intracranial pressure or cerebral metastasis. If this is suspected, a normal MR scan of the cerebrum are needed before inclusion 4. Radiologic confirmed ileus, or strong clinical suspicion evaluated by the study Investigator 5. Cognitive impairment or language barrier that makes the patient unable to complete the questionnaires 6. Surgery to the brain or abdomen within the last 2 weeks or exposure to general anesthesia within the last 4 days 7. Chemotherapy or radiation therapy within the last 4 weeks 8. Reversible causes of nausea/vomiting: e.g. Hypercalcemia (ion-calcium > 1,5), uremia (eGFR <20 ml/min), hypomagnesemia (p-mg < 0,50), newly commenced/changed opioid-therapy (within 7 days), other medication with emetic potential. 9. Pregnancy 10. Use of strong or moderate inhibitors of CYP3A4 within seven (7) days prior to administration of study drugs (see Section 11.2., “Inhibitors of CYP3A4”). 11. Use of inducers of CYP3A4 within thirty (30) days prior to the administration of study drugs (see Section 11.3., “Inducers of CYP3A4”).
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in nausea score If patients included because of vomiting: Change in number of emetic episodes |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and 24 hous following infusion |
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E.5.2 | Secondary end point(s) |
1. Two-item nausea score and CAT (computer adaptive testing)-score 2. Number of emetic episodes (vomit/dry retch). 3. Time to first emetic episode. 4. Nausea score measured daily for 7 days following administration of study medication 5. Number of emetic episodes measured daily for 7 days following the administration of study medication. 6. Tolerability. 7. Parameters indicative of efficacy: appetite, fatigue, pain, emotional function and overall quality of life. 8. Use of rescue anti-emetics.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: Baseline, 24 hours and after 7 days. 2 Baseline and 24 hours 3: Between 0-7 days 4: Daily from study day 0 to study day 7 5: Daily from study day 0 to study day 7 6: Daily from study day 0 to study day 7 7: Baseline and 7 days 8: Daily from study day 0 to study day 7 |
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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 | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
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 | No |
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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |