Clinical Trial Results:
A randomised, double-blind, placebo controlled, parallel study to assess the benefits of aclidinium bromide in the relief of COPD symptoms including cough when administered to patients with COPD
Summary
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EudraCT number |
2014-004715-37 |
Trial protocol |
DE GB HU IT ES |
Global end of trial date |
17 Nov 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Nov 2016
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First version publication date |
12 Nov 2016
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Other versions |
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 |
M-34273-46
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02375724 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Alternative sponsor identifier: D6560C00001 | ||
Sponsors
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Sponsor organisation name |
AstraZeneca
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Sponsor organisation address |
2 Kingdom St, London, United Kingdom, W2 6BD
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Public contact |
Study Director, AstraZeneca, ClinicalTrialTransparency@astrazeneca.com
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Scientific contact |
Study Director, AstraZeneca, ClinicalTrialTransparency@astrazeneca.com
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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 |
17 Nov 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Nov 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Nov 2015
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess the effect of aclidinium bromide 400 μg administered twice a day on COPD symptoms including cough and on cough-related quality of life measures in patients with moderate COPD compared to placebo
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Protection of trial subjects |
This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Conference on Harmonisation/Good Clinical Practice and applicable regulatory requirements and the AstraZeneca policy on Bioethics
Before enrolment into the study, all patients were comprehensively informed by the investigator (or the personnel identified as designated staff) orally and by means of the patient information sheet about the characteristics of the investigational medicinal products to be administered, the nature of the clinical investigation, the risks and the discomfort that could reasonably be expected as a result of their participation and about their right to withdraw at any time from the study, without prejudice and without any need to specify the reasons
Patients documented their willingness to participate in the study by giving their written consent by signing the Informed Consent Form before the start of any study procedure
Salbutamol pMDI (100 μg/puff) was allowed as relief medication
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Mar 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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: 115
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Country: Number of subjects enrolled |
Hungary: 88
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Country: Number of subjects enrolled |
Italy: 3
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Country: Number of subjects enrolled |
Spain: 27
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Country: Number of subjects enrolled |
United Kingdom: 36
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Worldwide total number of subjects |
269
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EEA total number of subjects |
269
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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) |
163
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From 65 to 84 years |
105
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85 years and over |
1
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Recruitment
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Recruitment details |
Patients were randomized in 30 study sites in 5 countries Germany (10 sites), Hungary (6), Italy (2), Spain (9) and the United Kingdom (3) First patient was enrolled in March 2015 and last patient last visit was in November 2015 | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
300 patients were screened; 269 were assessed as eligible and were randomized into the study Thirty-one patients failed screening, with the main reason for screening failure being non-fulfilment of the inclusion or exclusion criteria (24 patients) | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Investigator, Subject | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Aclidinium 400 μg | |||||||||||||||||||||||||||
Arm description |
Aclidinium bromide 400 μg BID administered by Genuair® multidose dry powder inhaler | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Aclidinium
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
1 puff of 400 μg in the morning (09:00±1 hour) and in the evening (21:00±1 hour)
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
Placebo BID administered by Genuair® multidose dry powder inhaler | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
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 |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
1 puff of 400 μg in the morning (09:00±1 hour) and in the evening (21:00±1 hour)
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Baseline characteristics reporting groups
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Reporting group title |
Aclidinium 400 μg
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Reporting group description |
Aclidinium bromide 400 μg BID administered by Genuair® multidose dry powder inhaler | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo BID administered by Genuair® multidose dry powder inhaler | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Aclidinium 400 μg
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Reporting group description |
Aclidinium bromide 400 μg BID administered by Genuair® multidose dry powder inhaler | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo BID administered by Genuair® multidose dry powder inhaler |
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End point title |
Change from baseline in overall Exacerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (E-RS) total score | ||||||||||||
End point description |
The EXACT-Respiratory Symptoms (E-RS) questionnaire was completed every evening
The E-RS scale is an instrument comprising a subset of EXACT items to test the effect of treatment on the severity of respiratory symptoms in stable COPD
Eleven of the 14-items of the EXACT questionnaire provides information about COPD symptoms: The E-RS Total Score is an aggregate of three domains: chest symptoms (derived sum of 3 items), cough and sputum (derived sum of 3 items) and RS-breathlessness (derived sum of 4 items)
Individual scores are rated from 0 to 4
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End point type |
Primary
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End point timeframe |
Week 8
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Statistical analysis title |
Aclidinium v Placebo | ||||||||||||
Comparison groups |
Aclidinium 400 μg v Placebo
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Number of subjects included in analysis |
264
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0306 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Least squares mean difference | ||||||||||||
Point estimate |
-1.02
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.94 | ||||||||||||
upper limit |
-0.1 |
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End point title |
Change from baseline in overall E-RS cough and sputum domain score | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Week 8
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Statistical analysis title |
Aclidinium v Placebo | ||||||||||||
Comparison groups |
Aclidinium 400 μg v Placebo
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Number of subjects included in analysis |
264
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0793 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Least squares mean difference | ||||||||||||
Point estimate |
-0.22
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.46 | ||||||||||||
upper limit |
0.03 |
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End point title |
Change from baseline in the Leicester Cough Questionnaire (LCQ) total score | ||||||||||||
End point description |
The LCQ is a self-administered questionnaire that assesses cough related quality of life
The LCQ comprises 19 items and 3 domains (physical, psychological and social)
The total score ranges from 3 to 21 and each domain scores range from 1 to 7; a higher score indicates a better quality of life
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End point type |
Secondary
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End point timeframe |
Week 8
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Statistical analysis title |
Aclidinium v Placebo | ||||||||||||
Comparison groups |
Aclidinium 400 μg v Placebo
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Number of subjects included in analysis |
254
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.844 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Least squares mean difference | ||||||||||||
Point estimate |
-0.06
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.64 | ||||||||||||
upper limit |
0.52 |
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Adverse events information
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Timeframe for reporting adverse events |
Day 70±3
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo BID administered by Genuair® multidose dry powder inhaler | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Aclidinium 400 μg
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Reporting group description |
Aclidinium bromide 400 μg BID administered by Genuair® multidose dry powder inhaler | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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05 Dec 2014 |
Correction included, as the Investigator Brochure was not provided along with the protocol and was available on request; Modification of the clarification note of inclusion criteria 1, as a serum pregnancy test was not performed in the study, but a urine pregnancy test was performed; Correction on the number of digits for site identification, as the first 5 digits representing the investigator identifier was replaced by the first 4 digits representing the site identifier |
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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 |