NCT02493283

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Sep 2011

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2011

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2012

Completed
2.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

June 30, 2015

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 9, 2015

Completed
Last Updated

July 9, 2015

Status Verified

July 1, 2015

Enrollment Period

9 months

First QC Date

June 30, 2015

Last Update Submit

July 6, 2015

Conditions

MethemoglobinemiaLinear IgA Bullous Dermatosis

Keywords

dapsoneblood leucocytespharmacokineticsmetabolism

Outcome Measures

Primary Outcomes (1)

  • Area under the curve (AUC) for dapsone (DDS) and MA-DDS

    AUC0-∞ for single dose administration and AUC0-24h for multiple dose

    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

Secondary Outcomes (14)

  • maximal serum concentration (Cmax) for dapsone (DDS) and MA-DDS

    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

  • minimal serum concentration (Cmin) for dapsone (DDS) and MA-DDS

    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

  • peak trough fluctuation (PTF) for dapsone (DDS) and MA-DDS

    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

  • timepoint of maximal serum concentration (Tmax) for dapsone (DDS) and MA-DDS

    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

  • terminal half live (T1/2) for dapsone (DDS) and MA-DDS

    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

  • +9 more secondary outcomes

Study Arms (2)

Treatment A

ACTIVE COMPARATOR

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 doseBiological: leucocytesBiological: Met-Hb

Treatment B

ACTIVE COMPARATOR

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 doseBiological: leucocytesBiological: Met-Hb

Interventions

Dapsone single doseDRUG

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)

Treatment A
Dapsone multiple doseDRUG

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)

Treatment B
leucocytesBIOLOGICAL

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

Treatment ATreatment B
Met-HbBIOLOGICAL

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

Treatment ATreatment B

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • years
  • 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

You may not qualify if:

  • 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
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald

Greifswald, Mecklenburg-Vorpommern, 17487, Germany

Location

MeSH Terms

Conditions

MethemoglobinemiaLinear IgA Bullous Dermatosis

Interventions

DapsoneLeukocyte Count

Condition Hierarchy (Ancestors)

Hematologic DiseasesHemic and Lymphatic DiseasesSkin Diseases, VesiculobullousSkin DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

SulfonesSulfur CompoundsOrganic ChemicalsBlood Cell CountCell CountCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisHematologic TestsInvestigative TechniquesCell Physiological PhenomenaBlood Physiological PhenomenaCirculatory and Respiratory Physiological Phenomena

Study Officials

  • Werner Siegmund, Prof

    Department of Clinical Pharmacology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 30, 2015

First Posted

July 9, 2015

Study Start

September 1, 2011

Primary Completion

June 1, 2012

Study Completion

March 1, 2015

Last Updated

July 9, 2015

Record last verified: 2015-07

Locations

DE(1)