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

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ClinicalTrials.gov Identifier: NCT02493283
Recruitment Status : Completed
First Posted : July 9, 2015
Last Update Posted : July 9, 2015
Sponsor:
Information provided by (Responsible Party):
University Medicine Greifswald

Brief 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

Condition or disease Intervention/treatment Phase
Methemoglobinemia Linear IgA Bullous Dermatosis Drug: Dapsone single dose Drug: Dapsone multiple dose Biological: leucocytes Biological: Met-Hb Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pharmacokinetics and Distribution of Dapsone (DDS) in Leucocytes After Single-dose and Multiple-dose Administration in Healthy Subjects Genotyped for CYP2C9 and NAT2 and in Patients With Autoimmune Bullous Dermatoses
Study Start Date : September 2011
Actual Primary Completion Date : June 2012
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Skin Conditions
Drug Information available for: Dapsone

Arm Intervention/treatment
Active Comparator: Treatment A
single-dose administration of 100 mg dapsone; sampling of blood, urine and feces; sampling for leucocytes collection and sampling for additional safety analyses (Met-Hb)
Drug: Dapsone single dose
Administration of two tablets Dapson-Fatol 50 mg Tabletten (= 100 mg dapsone) and sampling of blood (before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 h after single-dose administration), urine (0-24 h, 24-48 h, 48-72 h, 72-96 h, 96 -120 h) and feces (on treatment days 1-5)

Biological: leucocytes
sampling for leucocytes collection: study days -1, 1, 14 and 15

Biological: Met-Hb
sampling before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 h after single-dose administration, before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 h after last repeated-dose administration and sampling for additional safety analyses (Met-Hb): study days 10, 12, 14 and hematology on study day 12

Active Comparator: Treatment B
multiple-dose administration of 100 mg dapsone s.i.d. for 7 days; sampling of blood, urine and feces; sampling for leucocytes collection and sampling for additional safety analyses (Met-Hb)
Drug: Dapsone multiple dose
Administration of two tablets Dapson-Fatol 50 mg Tabletten (= 100 mg dapsone) s.i.d. for 7 days and sampling of blood (before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 h after last repeated-dose administration), urine (last treatment day 0-24 h) and feces (on treatment days 12-15)

Biological: leucocytes
sampling for leucocytes collection: study days -1, 1, 14 and 15

Biological: Met-Hb
sampling before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 h after single-dose administration, before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 h after last repeated-dose administration and sampling for additional safety analyses (Met-Hb): study days 10, 12, 14 and hematology on study day 12




Primary Outcome Measures :
  1. Area under the curve (AUC) for dapsone (DDS) and MA-DDS [ Time Frame: before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours after single-dose administration and before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after last repeated-dose administration ]
    AUC0-∞ for single dose administration and AUC0-24h for multiple dose


Secondary Outcome Measures :
  1. maximal serum concentration (Cmax) for dapsone (DDS) and MA-DDS [ Time Frame: before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours after single-dose administration and before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after last repeated-dose administration ]
  2. minimal serum concentration (Cmin) for dapsone (DDS) and MA-DDS [ Time Frame: before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after last repeated-dose administration on study-day 15 ]
  3. peak trough fluctuation (PTF) for dapsone (DDS) and MA-DDS [ Time Frame: before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after last repeated-dose administration on study-day 15 ]
  4. timepoint of maximal serum concentration (Tmax) for dapsone (DDS) and MA-DDS [ Time Frame: before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours after single -dose administration and before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after last repeated-dose administration ]
  5. terminal half live (T1/2) for dapsone (DDS) and MA-DDS [ Time Frame: before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours after single-dose administration and before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours after last repeated-dose administration ]
  6. renal clearance (CLR) for dapsone (DDS) and MA-DDS [ Time Frame: before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 and 120 hours after single-dose administration and before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 and 120 hours after last repeated-dose administration ]
  7. metabolic clearance (CLM) for dapsone (DDS) [ Time Frame: before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 and 120 hours after single-dose administration and before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 and 120 hours after last repeated-dose administration ]
  8. rate of adverse events [ Time Frame: participants will be followed for the duration of hospital stay (3 weeks) and up to 2 weeks after last study medication, an expected average of 5 weeks ]
  9. Met-Hb [ Time Frame: before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 on study day 1 and 14 and additional once on study day 10 and 12 ]
  10. leucocytes [ Time Frame: study day 12 ]
  11. erythrocytes [ Time Frame: study day 12 ]
  12. hemoglobin [ Time Frame: study day 12 ]
  13. hematocrit [ Time Frame: study day 12 ]
  14. platelets [ Time Frame: study day 12 ]


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02493283


Locations
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Germany
Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald
Greifswald, Mecklenburg-Vorpommern, Germany, 17487
Sponsors and Collaborators
University Medicine Greifswald
Investigators
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Principal Investigator: Werner Siegmund, Prof Department of Clinical Pharmacology
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Responsible Party: University Medicine Greifswald
ClinicalTrials.gov Identifier: NCT02493283    
Other Study ID Numbers: Dapson - 2010
First Posted: July 9, 2015    Key Record Dates
Last Update Posted: July 9, 2015
Last Verified: July 2015
Keywords provided by University Medicine Greifswald:
dapsone
blood leucocytes
pharmacokinetics
metabolism
Additional relevant MeSH terms:
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Methemoglobinemia
Skin Diseases
Skin Diseases, Vesiculobullous
Linear IgA Bullous Dermatosis
Hematologic Diseases
Autoimmune Diseases
Immune System Diseases
Dapsone
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Anti-Bacterial Agents