Aprepitant in histamine-refractory chronic pruritus: a multicenter, randomized, double-blind, placebo-controlled, cross-over, phase II trial (APREPRU)
- Conditions
- L28.1Prurigo nodularis
- Registration Number
- DRKS00005594
- Lead Sponsor
- niversitätsklinikum Münster
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 58
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
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).
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method intra-individual difference in visual analgo scale (VAS) at visit 4 minus Baseline visit 2, and at visit 7 minus Baseline” visit 5, respectively
- Secondary Outcome Measures
Name Time Method - intra-individual difference in verbal rating scale (VRS) at visit 4 minus Baseline visit 2, and at visit 7 minus Baseline” visit 5, respectively<br>- intra-individual difference in VAS at visit 4 minus Baseline visit 2, and at visit 7 minus Baseline” visit 5, respectively. <br>- Time course changes in VAS, VRS <br>- Time course changes in DLQI, HADS and ItchyQol<br>- PBI-P index at visits 4 and 5, and at visits 7 and 8, respectively, compared to Baseline visit 2<br><br>