Patients with generalized chronic pruritus (> 6 weeks duration) and showing prurigo nodularis refractory to pretreatment with antihistamines (normal dosage, four weeks) MedDRA version: 17.0 Level: LLT Classification code 10037084 Term: Prurigo nodularis System Organ Class: 100000004858 MedDRA version: 17.0 Level: LLT Classification code 10018123 Term: Generalized pruritus System Organ Class: 100000004858
Conditions
Interventions
Trade Name: EMEND® 80 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Aprepitant
Other descriptive name: APREPITANT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentrati
Sponsors
University Hospital Münster
Eligibility
Sex/Gender
All
Inclusion criteria
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: - 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 - bilateral tubal ligation - or hormonal intra-uterine device (IUD) inserted at least 1 month prior to Base-line visit AND use of preservative - 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 26 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26
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, hematopoiet-ic, renal, gastrointestinal or metabolic dysfunction and/or disease unless currently con-trolled 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 or phototherapie (washout period 4 weeks): ultraviolet A or B light therapie, 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, phenprocoumon, 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of aprepitant relative to placebo in reducing chronic pruritus according to the Patient Global Assessment (PGA) as measured by the Visual Ana-logue Scale (VAS, average itch, visit-obtained);Primary end point(s): Baseline-adjusted VAS (average itch, visit-obtained) according to the PGA; i.e., intra-individual difference in VAS at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5, respectively ;Timepoint(s) of evaluation of this end point: at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5;Secondary Objective: •To evaluate the efficacy of aprepitant relative to placebo in reducing chronic pruritus according to the PGA as measured by the -VRS concerning itch, burning, stinging (visit-obtained) -VAS (worst itch, visit-obtained) -Global and dynamic score (visit-obtained) -VRS concerning itch (diary-obtained) -NRS (average itch, diary-obtained) -NRS (worst itch, diary-obtained) -Global question concerning presence of pruritus (diary-obtained) •To evaluate the efficacy of aprepitant relative to placebo in reducing chronic pruritus as measured by the -DLQI (visit-obtained) -HADS (visit-obtained) -PBI-P (visit-obtained) -PAS of skin lesions of prurigo nodularis (visit-obtained) •To assess the safety of aprepitant •Subanalysis of response in atopic and non-atopic patients •To compare the results obtained by PAS and VAS with VRS and NRS in order to analyze the sensitivity of the tools and to validate the diary-obtained measurements | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Baseline-adjusted VRS concerning itch, burning, and stinging (visit-obtained) according to the PGA; i.e., intra-individual difference in VRS at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5, respectively 2. Baseline-adjusted VAS (worst itch, visit-obtained) according to the PGA; i.e., intra-individual difference in VAS at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5, respectively. 3. Global and dynamic score (visit-obtained) according to the PGA at visit 4 and at visit 7, respectively 4. Time course changes in VAS, VRS and Global/dynamic score according to the PGA (visit-obtained) 5. Time course changes in VRS concerning itch, NRS (average itch and worst itch), and global question concerning presence of pruritus according to the PGA (diary-obtained) 6. Time course changes in DLQI and HADS (visit-obtained) 7. PBI-P index (visit-obtained) at visits 4 and 5, and at visits 7 and 8, respectively, compared to Baseline visit 2 8. Baseline-adjusted PAS of skin lesions of prurigo nodularis (visit-obtained); i.e., intra-individual difference in PAS at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5, respectively; 9. Time course changes in PAS (visit-obtained) 10. Use of rescue medication ;Timepoint(s) of evaluation of this end point: 1. at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5 2.at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5 3. at visit 4 and at visit 7 4. - 5. - 6. - 7. at visits 4 and 5, and at visits 7 and 8 8. at visit 4 minus Baseline visit 2, and at visit 7 minus “Baseline” visit 5 9. - 10. - | — |
Countries
Germany
Contacts
Public ContactCompetence Center Chronic Pruritus
University Hospital Münster, Department of Dermatology
Outcome results
None listed