Immunesuppression
Conditions
Interventions
Trade Name: Prograf®
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: TACROLIMUS
CAS Number: 104987-11-3
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration
Sponsors
Centre for Human Drug Research
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing to give written informed consent and willing and able to comply with the study protocol; 2. Healthy male or female subjects, 18 to 55 years of age (inclusive) at screening. The health status is verified by absence of evidence of any clinical significant active or uncontrolled chronic disease following a detailed medical history and a complete physical examination including vital signs, laboratory measurements and 12-lead ECG; 3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and with a minimum bodyweight of 50 kg at screening; 4. All women of child bearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 90 days after their last dose of study treatment. 5. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any disease associated with immune system impairment, including auto-immune diseases, HIV, any confirmed history of severe allergic reaction and transplantation patients; 2. Evidence of any other active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator. Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance; 3. Clinically significant abnormalities, as judged by the investigator, in laboratory test results 4. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening, or other known infection requiring antibiotic therapy within the last three months prior to the study; 5. Use of any medications (prescription or over-the-counter [OTC]), within 21 days of study drug administration, or less than 5 half-lives (whichever is longer). 6. Received immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study; 7. Use of any vitamin, mineral, herbal, and dietary supplements within 7 days of study drug administration, or less than 5 half-lives (whichever is longer). 8. Use of grapefruit(juice), bitter lemon or tonic within 3 days of study drug administration; 9. Participation in an investigational drug or device study within 3 months prior to first dosing; 10. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 14 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillisers, or any other addictive agent; 11. Positive test for drugs of abuse at screening or pre-dose; 12. Alcohol will not be allowed from at least 24 hours before screening and every return visit; 13. Smoking cigarettes (or equivalent) and/or using nicotine based products within 3 months prior to study drug administration; 14. Is demonstrating excess in xanthine consumption (more than eight cups of coffee or equivalent per day); 15. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable); 16. Loss or donation of blood over 500 mL within three months prior to screening or intention to donate blood or blood products during the study; 17. If a woman, pregnant, or breast-feeding, or planning to become pregnant during the study; 18. Any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the pharmacokinetic profile of a single dose of tacrolimus; o Whole blood concentrations o Cellular concentrations (T cells and/or PBMCs) o Relationship between whole blood and cellular concentrations To investigate the pharmacodynamic effects of a single dose of tacrolimus; o Calcineurin activity o T cell function (activation, proliferation) To investigate the relationship between the pharmacokinetic profile of tacrolimus (in whole blood and intracellular) and the pharmacodynamic effects ex vivo; To investigate the correlation between pharmacodynamic effects (calcineurin activity and T cell function) in vitro and ex vivo; ;Secondary Objective: N.A.;Primary end point(s): Tolerability / safety endpoints: (Serious) adverse events ((S)AEs) will be collected throughout the study at every study visit. Laboratory safety and vital signs will be obtained multiple times during the course of the study according to the Visit and Assessment Schedule Pharmacokinetic endpoints: • Whole blood tacrolimus levels • Cellular tacrolimus levels in T-cells and/or PBMCs Pharmacodynamic endpoints: Drug effects will be monitored in vitro and ex vivo by: • Calcineurin activity • T cell proliferation • T cell activation (cell surface markers) • T cell activation (cytokine release) ;Timepoint(s) of evaluation of this end point: Day 0 - Day 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): N.A.;Timepoint(s) of evaluation of this end point: N.A. | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Centre for Human Drug Research
Outcome results
None listed