Trial document




drksid header

  DRKS00005594

Trial Description

start of 1:1-Block title

Title

Aprepitant in histamine-refractory chronic pruritus: a multicenter, randomized, double-blind, placebo-controlled, cross-over, phase II trial (APREPRU)

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

APREPRU

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

Chronic itching (pruritus) is a frequently occurring symptom with a massive negative impact on the quality of life of those affected. Currently available therapies are not very effective; there is, therefore, urgent need for discovering new therapeutic possibilities. The aim of the present study is to demonstrate the antipruritic properties of the neurokinin 1-receptor antagonist aprepitant on the basis of a randomized, placebo-controlled, phase II study in patients with chronic pruritus. The substance that blocks the activity of the neuropeptide substance P and thereby suppresses itching has already been tested on more than 100 patients with convincing success. What is missing so far is a comparison of the effectiveness of aprepitant with a group of patients treated only with a placebo. In four national Expert Centers, studies with a so-called cross-over design will be conducted in which patients will be treated with aprepitant and placebo. After a 4-week wash-out period, patients will assigned to one treatment group and will receive 80 mg aprepitant or placebo for 4 weeks. After a two-week pause, there will be a second treatment phase (placebo or 80 mg aprepitant for 4 weeks). In the course of the study, patients will be asked to assess several times the intensity and quality of pruritus, the therapeutic benefit and quality of life. Efficacy, safety and adverse effects will be monitored by regular patient visits, physical check-ups and blood analyses.
The study has high significance for the clinics practice and basic research. Worldwide, working groups have been observed with great interest the antipruritic effects of aprepitant with the result that it is already being increasingly used for treating patients with chronic pruritus. A confirmatory study will have a high influence on its further use in patient care and treatment. The results of the study will be communicated to the circle of national and international experts and societies and also to Guidelines Committees.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

Until today chronic pruritus cannot be treated sufficiently. Besides the excruciating symptom, affected patients go through a stigmatization because of the visible scratch lesions. Chronic pruritus has an enormous impact on their quality of life and reactive depressions or further psychosomatic symptoms are given because of the high refractory therapy and associated long duration of pruritus. An effective therapy could not only treat the symptom itself, but also physical and psychical concomitants. The neurokinin 1 receptor antagonist aprepitant is a very promising substance, which only has been examined to its antipruritic properties in case series, but not in clinical trials of high quality. The aim of this clinical trial is to investigate, to confirm and to evaluate qualitative and quantitative the antipruritic efficacy of aprepitant in a randomized, placebo-controlled, multicenter, cross over trial of high quality according to the current ICH-GCP-guidelines. Among change in pruritus intensity, important parameter for the evaluation under treatment are changes in the quality of life and the determination of the patients benefits via questionnaires (patients reported outcomes). Additionally the adverse effect and safety profile of the substance will be assessed over a 4-week-treatment.

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00005594
  •   2014/01/16
  •   [---]*
  •   yes
  •   Approved
  •   2013-584-f-A, Ethik-Kommission der Ärztekammer Westfalen-Lippe und der med. Fakultät der Westfälischen Wilhelms-Universität Münster
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   U1111-1140-6701 
  •   2013-001601-85 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   L28.1 -  Prurigo nodularis
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   -phase 1: screening: maximum of 4 weeks, then randomisation in two groups
    -phase 2 (treatment 1: 4 weeks): group 1: Aprepitant (80 mg, oral)
    -phase 3: wash out perios of two weeks
    -phase 4: (treatment 2: 4 Wochen): group 1: placebo (oral)
    -phase 5: follow-up period of two weeks
  •   -phase 1: screening: maximum of 4 weeks, then randomisation in two groups
    -phase 2 (treatment 1: 4 weeks): group 2: placebo ( oral)
    -phase 3: wash out perios of two weeks
    -phase 4: (treatment 2: 4 Wochen): group 2: Aprepitant (80 mg, oral)
    -phase 5: follow-up period of two weeks
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist, caregiver
  •   Placebo
  •   Treatment
  •   Crossover
  •   II
  •   Yes
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

intra-individual difference in visual analgo scale (VAS) at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5, respectively

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- intra-individual difference in verbal rating scale (VRS) at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5, respectively
- intra-individual difference in VAS at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5, respectively.
- Time course changes in VAS, VRS
- Time course changes in DLQI, HADS and ItchyQol
- PBI-P index at visits 4 and 5, and at visits 7 and 8, respectively, compared to Baseline visit 2

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2014/06/30
  •   58
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   70   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

1. Age: 18 - 70 years, both gender
2. Patients with generalized chronic pruritus (being actively present for at least 6 weeks prior to screening) AND showing prurigo nodularis of dermatological, systemic or mixed origin
3. Pruritus was refractory* to a four-week systemic antihistamine therapy (by history, any antihistamine; *no reduction of pruritus by more than two points on VAS)
4. VAS ≥ 7 (in average during one of the past two days) at Baseline
5. Signed informed consent
6. Male patients agree to use a reliable method of birth control during the study.
7. If the subject is a female of childbearing potential who:
- has been strictly abstinent 1 month prior to baseline (V2) and agrees to continue for the duration of the clinical trial and for 2 months after end of study
- and/or agrees to use a highly effective and approved contraceptive method(s) for the duration of the study and for 2 months after end of the study.
A highly effective method of contraception is defined as:
o combined oral contraceptives (estrogens and progesterone) or implanted or in-jectable contraceptives with a stable dose for at least 1 month prior to Baseline visit AND use of preservative or
o bilateral tubal ligation
o or hormonal intra-uterine device (IUD) inserted at least 1 month prior to Base-line visit AND use of preservative
o or vasectomized partner for at least 3 months prior to baseline
Or
Female of non-childbearing potential, defined as post menopausal (absence of menstrual bleeding for one year without any other medical reasons), hysterectomy or bilateral oophorectomy at Screening and Baseline visit

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

1. Patients with
a. chronic pruritus of paraneoplastic, neurogenic, and psychogenic origin
b. pruritus of dermatologic origin with severe skin inflammation necessitating systemic anti-inflammatory therapy, for example urticaria, bullous pemphigoid, acute generalized flaring up in atopic dermatitis.
c. localized pruritus (only a single area involved)
2. Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction and/or disease unless currently controlled and stable
3. Subjects with an underlying known disease, a surgical or medical condition, which in the judgement of the Investigator, would put the subjects at risk (e.g., uncontrolled chronic or serious diseases which would normally prevent participation in any clinical study or might confound the study assessments (e.g. other dermatological diseases), or might interfere with the subject’s study participation (e.g. planned hospitalization during the study) at Screening and Baseline visits
4. Subjects with clinically significant abnormal laboratory values according to the Investigator at Screening visit
5. Current psychosomatic and psychiatric diseases
6. Current malignant disease and chemotherapy (e.g., hodgkins lymphoma during therapy)
7. Chemotherapy with etoposide, vinorelbine
8. Current and past use of topical (washout period 2 weeks) or systemic steroids (washout period 4 weeks) before baseline
9. Current and past use before baseline of topical and systemic antihistamines such as cetirizine or loratadine (washout period 2 weeks) [remark: During the study the intake of cetirizine as rescue medication is allowed.]
10. Current and past use before baseline of the following systemic drugs (washout period 4 weeks): ultraviolet A or B light therapy, cyclosporin A and other immunosuppressants, antiepileptics (e.g., midazolam) and anti-cholinergics, antidepressants, pain modulators (gabapentin/pregabalin), opioid receptor agonists or antagonists, anti-anxiety drugs, tranquilizers, hypnotics, antipsychotic drugs (e.g., pimozide)
11. Current and past use before baseline and planned intake during the study of the following drugs (washout period 4 weeks):
- drugs strongly inducing CYP3A4 activity (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s Wort (Hypericum perforatum, “Johanniskraut”),
- ketoconazole, itraconazole, voriconazol, posaconazol, clarithromycin, telithromycin, nefazodon, protease inhibitors, irinotecan
- pimozid, terfenadine, astemizole, cisapride
- tacrolimus, sirolimus, everolimus, alfentanil, dihydroergotamin, ergotamin, fentanyl, chinidin
- warfarin, phenprcoumon, midazolam, alprazolam, triazolam, acenocoumarol, tolbutamide
12. Pregnancy, breast feeding
13. Subjects currently enrolled in another investigational drug or device study or participated in such a study in the month prior to Baseline visit.
14. Known hypersensitivity to aprepitant or to any of the excipients, especially sucrose (e.g. patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency).

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsklinikum Münster
    • Domagkstraße 5
    • 48149  Münster
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Kompetenzzentrum chronischer Pruritus (KCP) und Klinik für Hautkrankheiten Universitätsklinikum Münster
    • Ms.  Prof. Dr.  Sonja  Ständer 
    • Von-Esmarch-Str. 58
    • 48149  Münster
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Universitätsklinikum MünsterKlinik für HautkrankheitenZentrale Studienkoordination für innovative Dermatologie (ZiD)
    • Mr.  Dr.  Athanasios  Tsianakas 
    • Von-Esmarch-Str. 58
    • 48149  Münster
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bundesministerium für Bildung und Forschung Dienstsitz Bonn
    • Heinemannstr. 2
    • 53175  Bonn
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting complete, follow-up complete
  •   2016/01/04
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  •   Tsianakas A, Zeidler C, Riepe C, Borowski M, Forner C, Gerss J, Metz M, Staubach P, Raap U, Kaatz M, Urban M, Luger TA, Ständer S.: Aprepitant in Anti-histamine-refractory Chronic Nodular Prurigo: A Multicentre, Randomized, Double-blind, Placebo-controlled, Cross-over, Phase-II trial (APREPRU).Acta Derm Venereol. 2019 Jan 17. doi: 10.2340/00015555-3120.
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.