E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Colorectal carcinoma or other solid tumours |
Colorectal carcinoom of een ander type solide tumor |
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E.1.1.1 | Medical condition in easily understood language |
Colorectal carcinoma or other solid tumours |
Darmkanker of een ander vorm van solide tumor |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 |
1. To evaluate the area under the plasma concentration-time curve (AUC) of capecitabine alone, compared to capecitabine used with esomeprazole and compared with capacitabine used with esomeprazole and the acid beverage Coca-Cola Classic in patients with CRC or other solid tumours.
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Evalueren van de beschikbaarheid van capecitabine alleen, vergeleken met wanneer 3 uur voorafgaande aan de inname van capecitabine esomeprazol wordt ingenomen vergeleken en wanneer capecitabine wordt ingenomen met Coca-Cola 3 uur na inname van esomeprazol. |
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E.2.2 | Secondary objectives of the trial |
1. to study other PK parameters, including the clearance (CL), the maximum concentration (Cmax), and time of Cmax (tmax) of capecitabine. 2. to determine AUC, CL, Cmax and tmax of the metabolites of capecitabine: 5'-deoxy-5-fluorocytidine (5’-DFCR), 5'-deoxy-5-fluorouridine (5’-DFUR) and 5-FU. 3. to evaluate the incidence and severity of side- effects of treatment with capecitabine in the presence of esomeprazole alone and in the presence of esomeprazole combined with the acid beverage Coca-Cola Classic.
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Andere farmacokinetische uitkomstmaten zoals klaring, maximale concentratie, tijd tot maximale concentratie voor capecitabine en metabolieten5'-deoxy-5-fluorocytidine (5’-DFCR), 5'-deoxy-5-fluorouridine (5’-DFUR) and 5-FU. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years. 2. Histologically or cytologically confirmed diagnosis of a solid tumour for which capecitabine is an appropriate treatment option. 3. Planned treatment with capecitabine. 4. ECOG Performance Status ≤2 5. Able and willing to sign the informed consent form prior to screening evaluations. 6. No concurrent (over the counter) use of other acid reducing drugs (PPIs, H2As and/or antacids) other than esomeprazole 40 mg once daily during the study. 7. Abstain from acid beverage (on study days, except for the Coca-Cola in Phase C according to study procedures), grapefruit, grapefruit juice, grapefruit-related citrus fruits, herbal dietary supplements and herbal tea during the study period.
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Leeftijd 18 jaar of ouder, histologisch of cytologisch bewijs van een solide tumor, geplande behandeling met capecitabine, ECOG lager of gelijk aan 2, in staat en bereidwillig het toestemmingsformulier te ondertekenen, geen andere maagzuurremmers gebruiken tijdens de studie periode, geen andere zure drank dan alleen Coca-Cola tijdens de studieperiode. |
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E.4 | Principal exclusion criteria |
1. Prior treatment with capecitabine is allowed, however, patients with a documented history of ≥ grade 3 toxicities with capecitabine are excluded. 2. Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria) 3. Known serious illness or medical unstable conditions (e.g. instable diabetes mellitus) that could interfere with the study medication/liquid. 4. Patients who are clinical dependent of use of PPIs or other acid reducing drugs. 5. Known complete deficiency of dihydropyrimidine dehydrogenase (DPD) activity. 6. Known poor metabolizers of cytochrome P450 2C19. 7. Use of cytochrome P450 2C19/ 3A4 inducers and or inhibitors. 8. Use of medicines/supplements wich can interact by capecitabine or esomeprazole |
Bij eerdere behandeling met capecitabine geen gr 3 toxiciteit zijn opgetreden, geen bekend verminderd absorptie vermogen van de maag, bekende ernstige aandoeningen medisch instabiele conditie, complete deficiëntie van DPD, afhankelijkheid van maagzuurremmers, gebruik van inducers/remmers van P450 2C19/3A4, gebruik van medicatie die een interactie geeft met capecitabine en of esomeprazol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the area under the plasma concentration-time curve (AUC) of capecitabine alone, compared to capecitabine used with esomeprazole and compared with capacitabine used with esomeprazole and the acid beverage Coca-Cola Classic in patients with CRC or other solid tumours.
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Evalueren van de beschikbaarheid van capecitabine alleen, vergeleken met wanneer 3 uur voorafgaande aan de inname van capecitabine esomeprazol wordt ingenomen vergeleken en wanneer capecitabine wordt ingenomen met Coca-Cola 3 uur na inname van esomeprazol. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of study
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Einde van de studie |
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E.5.2 | Secondary end point(s) |
1. to study other PK parameters, including the clearance (CL), the maximum concentration (Cmax), and time of Cmax (tmax) of capecitabine. 2. to determine AUC, CL, Cmax and tmax of the metabolites of capecitabine: 5'-deoxy-5-fluorocytidine (5’-DFCR), 5'-deoxy-5-fluorouridine (5’-DFUR) and 5-FU. 3. to evaluate the incidence and severity of side- effects of treatment with capecitabine in the presence of esomeprazole alone and in the presence of esomeprazole combined with the acid beverage Coca-Cola Classic.
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Andere farmacokinetische uitkomstmaten zoals klaring, maximale concentratie, tijd tot maximale concentratie voor capecitabine en metabolieten5'-deoxy-5-fluorocytidine (5’-DFCR), 5'-deoxy-5-fluorouridine (5’-DFUR) and 5-FU. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of study |
Einde van de studie |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Esomeprazol/ Coca-Cola |
Esomeprazole/Coca-Cola |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.5 | 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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LVLS |
Laatste visite van de laatste patiënt. |
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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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |