The primary objective is to compare the pharmacokinetic profile of tacrolimus after rectal and sublingual administration with oral administration.
ID
Bron
Verkorte titel
Aandoening
Tacrolimus, rectal, sublingual, pharmacokinetics.
Tacrolimus, rectaal, sublinguaal, farmacokinetiek.
Ondersteuning
Maastricht University Medical Centre
P. Debyelaan 25
6229 HX Maastricht
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
Area under the blood concentration of tacrolimus – time curve (AUC).
Achtergrond van het onderzoek
Rationale:
Tacrolimus is an immunosuppressant drug that is used to prevent rejection of transplanted donor organs. Both oral and intravenous routes of administration are currently used in clinical practice. A need exists for alternative routes of administration, such as rectal or sublingual administration. These routes of administration have not been adequately assessed.
Objective:
To compare the pharmacokinetic profile of tacrolimus after rectal (suppository) and sublingual (powder) administration with oral (capsule) administration.
Study design:
Open, stratified, randomized, 3-way cross-over trial.
Study population:
Eighteen healthy volunteers, 18-65 years old.
Intervention:
Three single doses of tacrolimus will be administered in randomized order with an interval of at least 1 week:
1. A sublingual dose of 3 mg;
2. A rectal dose of 15 mg;
3. An oral dose of 7 mg.
Venous blood samples are drawn at prespecified time points.
Main study parameters/endpoints:
The area under the blood concentration-time curve (AUC) is used as main study parameter.
Secondary parameters are: Relative bioavailability, the time after administration when the maximum blood concentration is reached (tmax) and the elimination rate constant (kel).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The safety of single doses of tacrolimus has been well established. Volunteers may experience tacrolimus-related adverse effects. These adverse effects are generally mild and transient. During the trial, 42 venous blood samples are taken (a total of 196 ml blood). The trial comprises of 9 site visits. Volunteers will not benefit directly from participation.
Doel van het onderzoek
The primary objective is to compare the pharmacokinetic profile of tacrolimus after rectal and sublingual administration with oral administration.
Onderzoeksopzet
Three single doses of tacrolimus will be administered in randomized order with an interval of at least 1 week.
Onderzoeksproduct en/of interventie
Three single doses of tacrolimus will be administered in randomized order with an interval of at least 1 week:
1. A sublingual dose of 3 mg;
2. A rectal dose of 15 mg;
3. An oral dose of 7 mg.
Venous blood samples are drawn at prespecified time points.
Publiek
Maastricht University Medical Centre, Dept of Internal Medicine, Division of Nephrology,
P.Debyelaan 25,
Maastricht 6229 HX
The Netherlands
+31 (0)43 3875007
M.Christiaans@MUMC.nl
Wetenschappelijk
Maastricht University Medical Centre, Dept of Internal Medicine, Division of Nephrology,
P.Debyelaan 25,
Maastricht 6229 HX
The Netherlands
+31 (0)43 3875007
M.Christiaans@MUMC.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. Legally capacitated;
2. 18-65 years old;
3. Using adequate contraception (female volunteers of childbearing potential);
4. Able to comply with the study protocol and willing to give written informed consent.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
1. Concomitant use of medication, grapefruit juice or St John’s worth;
2. Smoking 10 or more cigarettes per day;
3. Simultaneous participation in another clinical trial;
4. Pregnancy or lactation (female volunteers);
5. Abnormal liver biochemistry (>2x upper normal limit);
6. Renal insufficiency (estimated creatinin clearance according to Cockroft-Gault < 70 mL/min);
7. Blood pressure > 160/100 mmHg, measured after at least 10 min rest in semi-recumbent position;
8. Prolonged QT interval, corrected for heart rate using the Bazett’s formula (women>470 ms, men>450 ms);
9. Active infection, as determined by clinical examination.
Opzet
Deelname
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
| Register | ID |
|---|---|
| NTR-new | NL2630 |
| NTR-old | NTR2758 |
| Ander register | MEC azM/UM / Drug Research Unit Maastricht : 11-2-004 / DRUM11-TACR; |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |