E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy volunteers. (Dicloxacillin is used against infections caused by beta-lactamase-producing organisms) Testing for drug-drug interactions caused by dicloxacillin. |
Raske frivillige. (Dicloxacillin bruges mod infektioner forårsaget af beta-laktamase producerende organismer). Tester for lægemiddelinteraktioner forårsaget af dicloxacillin. |
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E.1.1.1 | Medical condition in easily understood language |
Healthy volunteers. (Dicloxacillin is used against bacterial infections) Investigating if dicloxacillin causes drug-drug interactions when it is administered for a longer period of time. |
Raske frivillige.
(Dicloxacillin bruges mod bakterielle infektioner) Tester for om dicloxacillin forårsager lægemiddelinteraktioner når det gives i en længere periode. |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004035 |
E.1.2 | Term | Bacterial infection due to staphylococcus aureus |
E.1.2 | System Organ Class | 100000004862 |
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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 aim of this study is to investigate if treatment with dicloxacillin can lead to drug-drug interactions through induction of the efflux transporter P-glycoprotein (P-gp). |
Hovedformålet med studiet er at undersøge om behandling med dicloxacillin fører til lægemiddelinteraktioner gennem induktion af efflux transporteren P-glycoprotein (P-gp). |
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E.2.2 | Secondary objectives of the trial |
It will be investigated whether or not dicloxacillin induces its own metabolism. |
Det vil blive undersøgt om dicloxacillin inducerer sin egen metabolisme. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 18-55 years - The following data must be in the normal range or only clinical insignificantly different from this: eGFR, ALAT, bilirubin, HbA1c, hemoglobin - BMI >18.5 and < 30 kg/m2 - Bodyweight ≥ 50 kg - Non-smoker (abstained from smoking minimum 2 weeks before the first study day and during the trial) - Generally healthy - Willing to give informed consent |
- Alder 18-55 år - Nyrefunktion (eGFR), leverfunktion (ALAT, bilirubin), langtidsblodsukker (HbA1c) og blodmængde (hæmoglobin) i det normale interval eller uden væsentlig klinisk afvigelse herfra - Body Mass Index (BMI) >18,5 og < 30 kg/m - Ikke-ryger (har ikke røget i minimum 14 dage inden første forsøgsdag og gennem hele forsøgsperioden) - Godt helbred - Kropsvægt ≥ 50 kg - Villig til at afgive informeret samtykke |
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E.4 | Principal exclusion criteria |
- Known sensitivity to any of the used drugs or any excipients listed in section 6.1 in the Summary of Product Characteristics (SmPC). - Intake of any significant prescription drugs, over-the-counter drugs, herbal drugs, or dietary supplements*. Contraindicated drugs include: Anticoagulants, antiplatelet aggregation medicinal products, ticagrelor, clopidogrel, acetylsalicylic acid, chronic NSAIDs use, amiodarone, verapamil, systemic ketoconazole, clarithromycin, cyclosporin, itraconazole, tacrolimus, posaconazole, dronedarone, glecaprevir/pibrentasvir, quinidine, ritonavir, digoxin, selective serotonin reuptake inhibitors (SSRIs), selective serotonin norephinephrine reuptake inhibitors (SNRIs), pantoprazole, ranitidine, previous use of dicloxacillin or other P-gp or CYP450 inhibitors/inducers within 4 weeks prior to the start of treatment, probenecid, tetracycline, methotrexate - Alcohol abuse or if the Danish Health Authority recommendation regarding alcohol intake has been exceeded 2 weeks before the first study day (men 14 units alcohol/week, women 7 unites alcohol/week) - Participating in any other intervention trials - A positive pregnancy test at inclusion screening or any of the study days - Known penicillin allergy or reactions against cephalosporins, cephamycin, 1-oxa-ß-lactamer, or carbapenems - Women who are breastfeeding - Diagnosis of any of the following diseases (current or previous): Mechanical heart valve, congenital or acquired coagulation disorders, thrombocytopenia or functional platelet defects, biopsy within 4 weeks, major trauma, bacterial endocarditis, esophagitis, gastritis, gastroesophageal reflux, active meningitis, encephalitis, intracranial abscess, undergoing surgery, liver disease, history of thrombosis or diagnosed with antiphospholipid syndrome, active cancer
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- Kendt overfølsomhed over for de anvendte lægemidler eller nogle af de hjælpestoffer, der er nævnt i produktresumeet sektion 6.1 for lægemidlerne - Indtag af receptlægemidler, håndkøbslægemidler, naturlægemidler eller kosttilskud, der kan ændre effekten af lægemidler anvendt i forsøget*. Kontraindicerede lægemidler inkluderer: Antikoagulantia, blodpladehæmmende lægemidler, ticagrelor, clopidogrel, acetylsalicylsyre, kronisk anvendelse af NSAID’er, amiodaron, verapamil, quinidin, systemisk ketoconazol, clarithromycin, cyclosporin, itraconazol, tacrolimus, posaconazol, dronedaron, glecaprevir/pibrentasvir, ritonavir, digoxin, selektive serotonin-genoptagshæmmere (SSRI), selektive serotonin norephinephrine-genoptagshæmmere (SNRI), pantoprazol, ranitidin, probenicid, tetracyclin, methotrexat, tidligere brug af dicloxacillin eller andre P-gp eller CYP450 hæmmere/inducere indenfor de sidste 4 uger før forsøgsstart - Alkoholmisbrug eller hvis sundhedsmyndighedernes anbefalinger overskrides 14 dage inden forsøgsdagene (mænd 14 genstande/uge, kvinder 7 genstande/uge) - Deltagelse i et andet interventionsstudie - Positiv graviditetstest inden forsøgets start eller på de pågældende forsøgsdage - Kendt penicillin allergi eller overfølsomhed overfor cephalosporiner, cephamycin, 1-oxa-ß-lactamer eller carbapenemer - Kvinder der ammer - Diagnose af en af følgende sygdomme (nuværende eller tidligere): mekanisk hjerteklap, medfødt eller erhvervede koagulationsforstyrrelser, trombocytopeni eller blodpladefejl, biopsi 4 uger inden forsøgsstart, større traumer, bakteriel endokarditis, esophagitis, gastritis, gastroesophagael reflux, aktiv menigitis, encephalitis, intrakraniel abscess, gennemgår operation, leversygdom, fortid med blodprop eller diagnosticeret med antiphospholipidsyndrom, aktiv kræft |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change in AUC of the P-gp substrate dabigatran after 28 days of dicloxacillin treatment compared to baseline. |
Det primære endepunkt er ændring i AUC for P-gp substratet dabigatran efter 28 dages behandling med dicloxacillin sammenlignet med baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After the drug analysis is completed |
Nå lægemiddelanalysen er afsluttet |
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E.5.2 | Secondary end point(s) |
Changes in the full pharmacokinetics of the P-gp substrate dabigatran etexilate and all relevant metabolites after 10 and 28 days of dicloxacillin treatment compared to baseline. The concentrations will be determined from plasma and urine samples.
Changes in the full pharmacokinetics of dicloxacillin and its metabolites after 9 and 27 days of dicloxacillin treatment compared to baseline. This will be measured as concentrations in plasma and urine samples.
Changes in biomarkers of DMET after 10 and 28 days of dicloxacillin treatment compared to baseline.
Changes in exosome-derived biomarkers after 10 and 28 days of dicloxacillin treatment compared to baseline. |
Ændringer i farmakokinetikken for P-gp substratet dabigatran etexilate og alle dets relevante metabolitter efter 10 og 28 dages dicloxacillin behandling sammenlignet med baseline. Koncentrationen bliver målt i plasma og urinprøver.
Ændringer i farmakokinetikken af dicloxacillin og dets metabolitter efter 9 og 27 dages behandling med dicloxacillin sammenlignet med baseline. Koncentrationen bliver målt i plasma og urinprøver.
Ændring i biomarkører for DMET efter 10 of 28 dages dicloxacillin behandling sammenlignet med baseline.
Ændring i exosome-biomarkører efter 10 og 28 dages behandling med dicloxacillin sammenlignet med baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After the drug analysis is completed |
Når lægemiddelanalysen er afsluttet |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Pharmacokinetic trial |
Farmakokinetisk forsøg |
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Selv-kontrolleret |
Self-controlled |
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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
| 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. LVLS is defined as the day for the phone call 2 weeks after the last visit from the last trial subject. |
LVLS. LVLS er defineret som dagen for opringningen, 2 uger efter det sidste besøg fra den sidste forsøgsdeltager. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | |