MethemoglobinemiaPhase 1NCT02493283
Pharmacokinetics and Distribution of Dapsone in Leucocytes After Single-dose and Multiple-dose Administration
A Phase 1 study testing Dapsone single dose, Dapsone multiple dose and leucocytes in people with Methemoglobinemia and Linear IgA Bullous Dermatosis, run by University Medicine Greifswald at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Methemoglobinemia, Linear IgA Bullous Dermatosis
- What is being tested?
- Dapsone single dose, Dapsone multiple dose and leucocytes
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteGermany
- Study dates
- Sep 2011to Mar 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald
Greifswald, Mecklenburg-Vorpommern, 17487
About this study
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
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
Read the detailed description
Dapsone (diamino diphenyl sulphone, DDS) was synthesized by Emil Fromm and Jakob Wittmann in Freiburg (Germany) in 1908. In 1937, the anti-inflammatory potency of dapsone was discovered in experimentally-induced infections in mice. Since 1941, dapsone (as Promin®) is used with great success in the therapy of leprosy. Dapsone is a mainstay in the treatment of leprosy, being one of the components of the multidrug regimen advised by the World Health Organization (WHO).
In 1950, Esteves and Brandão confirmed the efficacy of the drug in patients with dermatitis herpetiformis Duhring. Sneddon and Wilkinson in England reported a remission as caused by dapsone in a patient with subcorneal pustulosis. The efficacy of dapsone in treatment of pemphigus vulgaris was initially reported by Winkelmann and Roth in 1960.
After oral administration, dapsone is almost completely absorbed from the gastrointestinal tract with bioavailability of more than 86 %. Maximum serum concentrations between 0,63 and 4,82 mg/l are attained within 2-8 hours after single doses between 50 mg and 300 mg. At steady-state, the serum concentration fluctuate between 3,26 mg/l and 1,95 mg/l chronic treatment with 100 mg dapsone once daily (s.i.d.).
Dapsone is distributed to all organs, it crosses the blood-brain barrier and placenta and is detected in breast milk.
About 20% of dapsone is excreted unchanged into the urine, 70-85% as water-soluble metabolites additionally to a small amount in feces.
Dapsone is nearly completely metabolized in the liver and in activated polymorphic neutrophils (PMN) and/or mononuclear cells. The major metabolic pathway in the liver is N-acetylation by the polymorphic N-acetyltransferase 2 (NAT2) and N-oxidation by cytochrome P-450 (CYP) enzymes. Major metabolites are monoacetyl-dapsone (MADDS) and dapsone hydroxylamine (DDS-NOH). Dapsone undergoes enterohepatic circulation.
MADDS is subjected also to significant deacetylation. A constant equilibrium between acetylation and deacetylation is reached within a few hours after the oral administration of either dapsone or MADDS. The acetylation ratio shows a large interindividual variation, ranging from 0.1 to 2.0. These ratios show a bimodal distribution pattern.
Acetylation is not the rate-determining step in overall elimination of dapsone. The amount of MADDS excreted in urine is very low because it is largely deacetylated to dapsone before excretion into the urine. Between slow acetylators (SA) and rapid acetylators (RA), there are no differences neither in dapsone serum concentrations nor any pharmacokinetic parameters of dapsone. Also, the therapeutic response is the same in both acetylator phenotypes.
However, excretion of both MADDS and its conjugated derivatives is higher in RA. Therefore, dapsone may be used for determination of the NAT2 phenotype even though these metabolites represent only a very small fraction of the dose.
MADDS is highly bound to plasma proteins (> 98%), about 20-25 times more tightly than dapsone. Presumably, the small fraction of unbound MADDS and its strong binding to plasma proteins are reasons for its low availability in erythrocytes (erythrocyte/plasma ratio = 0.33). Tight protein binding is also the reason behind low glomerular filtration rate of the metabolite; therefore the half-life for MADDS is approximately 20-25 hours, similar like for dapsone.
Microsomal N-hydoxylation is the second major metabolic route of dapsone which seems to be associated with hematological side effects of the drug. However, the data on excretion of free and conjugated DDS-NOH vary widely in the literature. No reliable information is available on excretion of hydroxylated MADDS compounds.
In terms of efficacy and safety of dapsone, most important is the generation of DDS-NOH, that also occurs in inflamed lesions of the skin as mediated by activated PMN. Thus, over the years, dapsone became a first-line drug in the treatment of dermatitis herpetiformis Duhring, Sneddon-Wilkinson-Syndrome and further bullous autoimmune dermatoses. Most recently was found, that formation of DDS-NOH is mainly under control of CYP2C9 in-vitro.(Lit.) Because of the known CYP2C9 gene polymorphisms (about 4-6 % are poor metabolizers, PM), efficacy of the drug in bullous autoimmune dermatoses may be dependent on the metabolizer status of the patients.
The investigators hypothesize, that subjects which are slow acetylators of NAT2 (SA) but extensive metabolizers of CYP2C9 (EM) may form significantly higher levels of the active metabolite DDS-NOH than rapid acetylators of NAT2 (RA) being PM of CYP2C9 (PM).
- Conditions
- Methemoglobinemia, Linear IgA Bullous Dermatosis
- Being tested
- Dapsone single dose, Dapsone multiple dose, leucocytes, Met-Hb
- Keywords
- dapsone, blood leucocytes, pharmacokinetics, metabolism
- Medical subject headings
- Methemoglobinemia, Linear IgA Bullous Dermatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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)
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)
leucocytesBiological
sampling for leucocytes collection: study days -1, 1, 14 and 15
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
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Dapsone single dose; Biological: leucocytes; Biological: 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) Receives: Drug: Dapsone multiple dose; Biological: leucocytes; Biological: Met-Hb |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve (AUC) for dapsone (DDS) and MA-DDS
AUC0-∞ for single dose administration and AUC0-24h for multiple dose
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
renal clearance (CLR) for dapsone (DDS) and MA-DDS
Measured: 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
metabolic clearance (CLM) for dapsone (DDS)
Measured: 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
rate of adverse events
Measured: 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
Met-Hb
Measured: 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
leucocytes
Measured: study day 12
erythrocytes
Measured: study day 12
hemoglobin
Measured: study day 12
hematocrit
Measured: study day 12
platelets
Measured: study day 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2015 (estimated)
- Study startSep 2011
- Primary completionJun 2012
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MethemoglobinemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medicine Greifswald
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Werner Siegmund, Prof, Principal investigator, Department of Clinical Pharmacology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02493283
- Sponsor's protocol ID
- Dapson - 2010
- Status last verified
- Jul 2015
- First submitted
- 30 Jun 2015
- Last updated
- 9 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02493283
- Acronym / sponsor ID
- Dapson - 2010
- Conditions
- Methemoglobinemia, Linear IgA Bullous Dermatosis
- Keywords
- dapsone, blood leucocytes, pharmacokinetics, metabolism
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University Medicine GreifswaldUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 9 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Dapsone (diamino diphenyl sulphone, DDS) was synthesized by Emil Fromm and Jakob Wittmann in Freiburg (Germany) in 1908. In 1937, the anti-inflammatory potency of dapsone was discovered in experimentally-induced infections in mice. Since 1941, dapsone (as Promin®) is used with great success in the therapy of leprosy. Dapsone is a mainstay in the treatment of leprosy, being one of the components of the multidrug regimen advised by the World Health Organization (WHO).
In 1950, Esteves and Brandão confirmed the efficacy of the drug in patients with dermatitis herpetiformis Duhring. Sneddon and Wilkinson in England reported a remission as caused by dapsone in a patient with subcorneal pustulosis. The efficacy of dapsone in treatment of pemphigus vulgaris was initially reported by Winkelmann and Roth in 1960.
After oral administration, dapsone is almost completely absorbed from the gastrointestinal tract with bioavailability of more than 86 %. Maximum serum concentrations between 0,63 and 4,82 mg/l are attained within 2-8 hours after single doses between 50 mg and 300 mg. At steady-state, the serum concentration fluctuate between 3,26 mg/l and 1,95 mg/l chronic treatment with 100 mg dapsone once daily (s.i.d.).
Dapsone is distributed to all organs, it crosses the blood-brain barrier and placenta and is detected in breast milk.
About 20% of dapsone is excreted unchanged into the urine, 70-85% as water-soluble metabolites additionally to a small amount in feces.
Dapsone is nearly completely metabolized in the liver and in activated polymorphic neutrophils (PMN) and/or mononuclear cells. The major metabolic pathway in the liver is N-acetylation by the polymorphic N-acetyltransferase 2 (NAT2) and N-oxidation by cytochrome P-450 (CYP) enzymes. Major metabolites are monoacetyl-dapsone (MADDS) and dapsone hydroxylamine (DDS-NOH). Dapsone undergoes enterohepatic circulation.
MADDS is subjected also to significant deacetylation. A constant equilibrium between acetylation and deacetylation is reached within a few hours after the oral administration of either dapsone or MADDS. The acetylation ratio shows a large interindividual variation, ranging from 0.1 to 2.0. These ratios show a bimodal distribution pattern.
Acetylation is not the rate-determining step in overall elimination of dapsone. The amount of MADDS excreted in urine is very low because it is largely deacetylated to dapsone before excretion into the urine. Between slow acetylators (SA) and rapid acetylators (RA), there are no differences neither in dapsone serum concentrations nor any pharmacokinetic parameters of dapsone. Also, the therapeutic response is the same in both acetylator phenotypes.
However, excretion of both MADDS and its conjugated derivatives is higher in RA. Therefore, dapsone may be used for determination of the NAT2 phenotype even though these metabolites represent only a very small fraction of the dose.
MADDS is highly bound to plasma proteins (> 98%), about 20-25 times more tightly than dapsone. Presumably, the small fraction of unbound MADDS and its strong binding to plasma proteins are reasons for its low availability in erythrocytes (erythrocyte/plasma ratio = 0.33). Tight protein binding is also the reason behind low glomerular filtration rate of the metabolite; therefore the half-life for MADDS is approximately 20-25 hours, similar like for dapsone.
Microsomal N-hydoxylation is the second major metabolic route of dapsone which seems to be associated with hematological side effects of the drug. However, the data on excretion of free and conjugated DDS-NOH vary widely in the literature. No reliable information is available on excretion of hydroxylated MADDS compounds.
In terms of efficacy and safety of dapsone, most important is the generation of DDS-NOH, that also occurs in inflamed lesions of the skin as mediated by activated PMN. Thus, over the years, dapsone became a first-line drug in the treatment of dermatitis herpetiformis Duhring, Sneddon-Wilkinson-Syndrome and further bullous autoimmune dermatoses. Most recently was found, that formation of DDS-NOH is mainly under control of CYP2C9 in-vitro.(Lit.) Because of the known CYP2C9 gene polymorphisms (about 4-6 % are poor metabolizers, PM), efficacy of the drug in bullous autoimmune dermatoses may be dependent on the metabolizer status of the patients.
The investigators hypothesize, that subjects which are slow acetylators of NAT2 (SA) but extensive metabolizers of CYP2C9 (EM) may form significantly higher levels of the active metabolite DDS-NOH than rapid acetylators of NAT2 (RA) being PM of CYP2C9 (PM).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Active comparator | Drug: Dapsone single dose, Biological: leucocytes, Biological: Met-Hbsingle-dose administration of 100 mg dapsone; sampling of blood, urine and feces; sampling for leucocytes collection and sampling for additional safety analyses (Met-Hb) |
| Treatment B | Active comparator | Drug: Dapsone multiple dose, Biological: leucocytes, Biological: Met-Hbmultiple-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) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapsone single doseAdministration 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) | Drug | Treatment A |
| Dapsone multiple doseAdministration 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) | Drug | Treatment B |
| leucocytessampling for leucocytes collection: study days -1, 1, 14 and 15 | Biological | Treatment A, Treatment B |
| Met-Hbsampling 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 | Biological | Treatment A, Treatment B |
Primary outcome
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
14 secondary outcomes
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
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
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
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
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
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
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
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
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
leucocytes
Time frame: study day 12
erythrocytes
Time frame: study day 12
hemoglobin
Time frame: study day 12
hematocrit
Time frame: study day 12
platelets
Time frame: study day 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2015.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Werner Siegmund, Prof principal investigator
Department of Clinical Pharmacology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dapsone single dose, Dapsone multiple dose and leucocytes in people with Methemoglobinemia and Linear IgA Bullous Dermatosis, run by University Medicine Greifswald at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2015.