Clinical Trial Results:
Aprepitant in histamine-refractory chronic pruritus: a multicenter, randomized, double-blind, placebo-controlled, cross-over, phase II trial
Summary
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EudraCT number |
2013-001601-85 |
Trial protocol |
DE |
Global end of trial date |
04 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jan 2017
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First version publication date |
08 Jan 2017
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Other versions |
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Summary report(s) |
APREPRU |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
UKM10_0037
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
U1111-1140-6701 | ||
Sponsors
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Sponsor organisation name |
University Hospital Münster
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Sponsor organisation address |
Von-Esmach-Str. 58, Münster, Germany, 48149
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Public contact |
Competence Center Chronic Pruritus, University Hospital Münster, Department of Dermatology, sonja.staender@ukmuenster.de
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Scientific contact |
Competence Center Chronic Pruritus, University Hospital Münster, Department of Dermatology, sonja.staender@ukmuenster.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Nov 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Jan 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Jan 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
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)
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Protection of trial subjects |
None
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Background therapy |
Patients were allowed to use emollients including urea which is known to have antipruritic properties in addition to the trial medication. Any other medication taken for any medical condition had to be documented in the patient`s file. If patients needed systemic rescue medication, cetirizine had to be used and documented in the patient´s file. This was not a drop-out criterion but was analyzed as secondary endpoint. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Jun 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 58
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Worldwide total number of subjects |
58
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EEA total number of subjects |
58
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
46
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From 65 to 84 years |
12
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85 years and over |
0
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Recruitment
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Recruitment details |
58 patients were recruited at 5 centers within Germay (Muenster, Gera, Mainz, Berlin, Hannover). | |||||||||||||||
Pre-assignment
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Screening details |
67 patients were screened, of which 58 were enrolled. | |||||||||||||||
Period 1
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Period 1 title |
Baseline
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Aprepitant in first period, placebo in second period | |||||||||||||||
Arm description |
The patients in this arm received aprepitant in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received placebo in the second treatment-period (daily, 4 weeks). | |||||||||||||||
Arm type |
Cross-over arm A | |||||||||||||||
Investigational medicinal product name |
Aprepitant
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
80mg , once daily
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Arm title
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Placebo in first period, aprepitant in second period | |||||||||||||||
Arm description |
The patients in this arm received placebo in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received aprepitant in the second treatment-period (daily, 4 weeks). | |||||||||||||||
Arm type |
Cross-over arm B | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
One capsula daily
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Period 2
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Period 2 title |
First treatment-period
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Investigator, Monitor, Data analyst, Carer, Assessor, Subject | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Aprepritant in first period, placebo in second period | |||||||||||||||
Arm description |
The patients in this arm received aprepitant in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received placebo in the second treatment-period (daily, 4 weeks). | |||||||||||||||
Arm type |
Cross-over arm A | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Placebo in first period, aprepritant in second period | |||||||||||||||
Arm description |
The patients in this arm received placebo in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received aprepritant in the second treatment-period (daily, 4 weeks). | |||||||||||||||
Arm type |
Cross-over arm B | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Period 3
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Period 3 title |
Second treatment-period
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Aprepritant in first period, placebo in second period | |||||||||||||||
Arm description |
The patients in this arm received aprepitant in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received placebo in the second treatment-period (daily, 4 weeks). | |||||||||||||||
Arm type |
Cross-over arm A | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Placebo in first period, aprepritant in second period | |||||||||||||||
Arm description |
The patients in this arm received placebo in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received aprepritant in the second treatment-period (daily, 4 weeks). | |||||||||||||||
Arm type |
Cross-over arm B | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: After the end of treatment-period 1, a two-week wash-out period started. Some patients dropped out during the wash-out period. |
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Baseline characteristics reporting groups
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Reporting group title |
Aprepitant in first period, placebo in second period
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Reporting group description |
The patients in this arm received aprepitant in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received placebo in the second treatment-period (daily, 4 weeks). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo in first period, aprepitant in second period
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Reporting group description |
The patients in this arm received placebo in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received aprepitant in the second treatment-period (daily, 4 weeks). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Aprepitant in first period, placebo in second period
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Reporting group description |
The patients in this arm received aprepitant in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received placebo in the second treatment-period (daily, 4 weeks). | ||
Reporting group title |
Placebo in first period, aprepitant in second period
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Reporting group description |
The patients in this arm received placebo in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received aprepitant in the second treatment-period (daily, 4 weeks). | ||
Reporting group title |
Aprepritant in first period, placebo in second period
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Reporting group description |
The patients in this arm received aprepitant in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received placebo in the second treatment-period (daily, 4 weeks). | ||
Reporting group title |
Placebo in first period, aprepritant in second period
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Reporting group description |
The patients in this arm received placebo in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received aprepritant in the second treatment-period (daily, 4 weeks). | ||
Reporting group title |
Aprepritant in first period, placebo in second period
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Reporting group description |
The patients in this arm received aprepitant in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received placebo in the second treatment-period (daily, 4 weeks). | ||
Reporting group title |
Placebo in first period, aprepritant in second period
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Reporting group description |
The patients in this arm received placebo in the first treatment-period (daily, 4 weeks). After a wash-out period (2 weeks), the patients received aprepritant in the second treatment-period (daily, 4 weeks). |
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End point title |
Primary efficacy endpoint of treatment-period 1 (PE1) [1] | ||||||||||||
End point description |
The PE1 was the intra-individual difference of the reported VAS (average itch during the past 24h, ranging from 0= "no itch" to 100="worst imaginable itch") at the beginning and at the end of the treatment-period 1. A negative PE1 therefore means an itch relief during treatment-period 1.
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End point type |
Primary
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End point timeframe |
The primary efficacy endpoint PE1 was measured in treatment-period 1.
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary efficacy analysis was conducted considering CROS(PE)=PE1-PE2. |
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No statistical analyses for this end point |
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End point title |
Primary efficacy endpoint of treatment-period 2 (PE2) [2] | ||||||||||||
End point description |
The PE2 was the intra-individual difference of the reported VAS (average itch during the past 24h, ranging from 0= "no itch" to 100="worst imaginable itch") at the beginning and at the end of the treatment-period 2. A negative PE2 therefore means an itch relief during treatment-period 2.
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End point type |
Primary
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End point timeframe |
The primary efficacy endpoint PE2 was measured in treatment-period 2.
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary efficacy analysis was conducted considering CROS(PE)=PE1-PE2. |
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No statistical analyses for this end point |
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End point title |
CROS(PE)=PE1-PE2 | ||||||||||||
End point description |
The primary efficacy analysis was conducted considering the intra-individual difference of PE1 and PE2, denoted as CROS (PE)= PE1 – PE2.
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End point type |
Primary
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End point timeframe |
CROS(PE) is the difference of PE1 and PE2, which were measured during treatment-period 1 and 2.
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Statistical analysis title |
Primary efficacy analysis (Intention-to-Treat) | ||||||||||||
Statistical analysis description |
For each patient, the intra-individual difference CROS(PE) = PE1 – PE2 was calculated. The two arms A (aprepitant in treatment-period 1, placebo in treatment-period 2) and B (placebo in treatment-period 1, aprepitant in treatment-period 2) were compared regarding CROS(PE) by a stratified Wilcoxon-Mann-Whitney test (van Elteren-test) on a two-sided significance level of 5% with strata defined by the patients’ atopic/non-atopic predisposition.
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Comparison groups |
Aprepritant in first period, placebo in second period v Placebo in first period, aprepritant in second period
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Number of subjects included in analysis |
50
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | ||||||||||||
P-value |
= 0.742 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Notes [3] - This was an intention-to-treat analysis that was conducted considering all patients who were randomized (full-analysis set). |
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Adverse events information
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Timeframe for reporting adverse events |
From first Patient in until last Patient out.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18
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Reporting groups
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Reporting group title |
Under aprepitant
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Reporting group description |
This reporting group includes all adverse events that occurred in patients in arm A during treatment-period 1 (under aprepitant) and during the wash-out period, and all adverse events that occurred in patients in arm B during and after treatment-period 2 (under aprepitant). | |||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Under placebo
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Reporting group description |
This reporting group includes all adverse events that occurred in patients in arm B during treatment-period 1 (under placebo) and during the wash-out period, and all adverse events that occurred in patients in arm A during and after treatment-period 2 (under placebo). | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0.05% | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |