Pharmacokinetics and Distribution of Dapsone in Leucocytes After Single-dose and Multiple-dose Administration

• Status: Completed
• Trial end date: 2015-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The objectives of the study are

• to evaluate pharmacokinetics, distribution in blood leucocytes, metabolism and methemoglobinemia after single-dose and repeated-dose administration of 100 mg of dapsone in healthy subjects genotyped for CYP2C9 and NAT2

• to evaluate serum through levels, distribution in blood leucocytes and methemoglobinemia after repeated-dose treatment with dapsone in patients with autoimmune bullous dermatoses before and after concomitant treatment with glucocorticoids

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Medicine Greifswald
• Treatments: Dapsone

Criteria

Inclusion Criteria:

• 18 - 45 years

• preferably males (females will be included if there are not enough males which fulfill the inclusion criteria)

• Caucasian

• body weight: > 19 kg/m² and < 27 kg/m²

• good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state

• written informed consent given by volunteer after being provided with detailed information about the nature, risks, and scope of the clinical trial as well as the expected desirable and adverse effects of the drug

Exclusion Criteria:

• results of the medical examination or laboratory screening which are judged by the clinical investigator to differ in a clinically relevant way from the normal state

• female subjects not willing to apply a highly effective method of birth control, which means contraceptive methods with a low failure rate of less than 1% per year during the entire study as stated in the Note for Guidance on Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals (CPMP/ICH/286/95, modifications). These methods include implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.

• subjects with existing cardiac or hematological diseases and/ or pathological findings which might interfere with safety, pharmacodynamic effect and/ or pharmacokinetics of dapsone

• subjects with existing gastrointestinal diseases and/ or pathological findings which might interfere with safety, pharmacodynamic effect and/ or pharmacokinetics of dapsone

• subjects with acute or chronic organ diseases which could affect drug absorption, metabolism or excretion of dapsone and its metabolites

• subjects liable to orthostatic dysregulation, fainting, or blackout

• subjects with known allergic reactions to the investigational product and its adjuvants

• deficiency of glucose-6-phosphate dehydrogenase (G6PD)

• subjects positive of HBsAG, HIV and /or drugs

• subjects with history of psychiatric disorders (depressions, other psychotic disorders)

• subjects with history of epilepsy

• gravidity

• breast feeding mothers, lactation

• alcohol consumption more than 20 g/day

• special or uniform nutritional habits, e.g. vegetarians or undercaloric diet

• intake of grapefruit containing food or beverages and poppy seeds containing products (will not be allowed) 14 days prior to the first drug administration (and) until the last blood sampling of the study

• subjects with uncommon physical exercise (competitive athletes), excessive physical activity one week before the trial

• excessive smoking (more than 10 cigarettes or equivalents per day)

• less than 14 days after last acute disease

• less than 14 days after last systemic or local drug administration or less than 10 half-lives of the respective drugs

• blood donation within the last 3 months

• blocking time due to another clinical trial with investigational products

• subjects suspected or known not to follow instructions

• subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study