Prophylaxis of the rejection of an allogeneic organ Immunosuppression
Conditions
Interventions
Mycophenolate mofetil, a single oral dose (2 tablets of 500 mg) or matching
placebo.
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Eligible subjects must meet all of the following inclusion criteria at screening: 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; 4. All women of child bearing potential and all males 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. All women of child bearing potential must be willing to take a pregnancy test at screening, check-in and follow-up. Men cannot donate any sperm during the study and for three months after EOS. 6. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.
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 (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG) at screening or pre-dose). 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 (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis) at screening or pre-dose. In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects; 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). Exception is paracetamol (up to 4 g/day). Other exceptions will only be made if the rationale is clearly documented by the investigator; 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). Exceptions will only be made if the rationale is clearly documented by the investigator; 8. Participation in an investigational drug or device study within 3 months prior to first dosing; 9. 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; 10. Positive test for drugs of abuse at screening or pre-dose; 11. Alcohol will not be allowed from at least 24 hours before screening and every return visit, and during unit stay; 12. Smoking cigarettes (or equivalent) and/or using nicotine based products within 3 months prior to study drug administration; 13. Is demonstrating excess in xanthine consumption (more than eight cups of coffee or equivalent per day) from 7 days prior to the first dose of the study drug until EOS; 14. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable); 15. 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 and up until 6 weeks after the EOS; 16. If a woman, pregnant, or breast-feeding, or planning to become pregnant during the study; 17. Any known factor, condition, or disease that might interfere with treatmen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 - Plasma MPA levels - Cellular MPA levels in T-cells and/or PBMCs Pharmacodynamic endpoints Drug effects will be monitored by: - T cell proliferation - Cytokine production In addition, the drug concentration * response relationship will be determined in vitro for each individual participant at baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory endpoints - Effect of single dose of MMF on B cell proliferation | — |
Countries
Netherlands
Outcome results
None listed