Clinical Trial Results:
Multicenter, randomized, blinded, two-period cross-over study to assess the effect of glycopyrronium (44 micrograms QD) versus tiotropium (18 micrograms QD) on morning symptoms and pulmonary function in patients with moderate to severe COPD.
Due to EudraCT system limitations, which EMA is aware of, results of crossover studies are not accurately represented in this record. Please go to https://www.novctrd.com/CtrdWeb/home.nov for complete trial results.
Summary
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EudraCT number |
2013-002483-84 |
Trial protocol |
DE GB IT ES |
Global end of trial date |
27 Oct 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Jul 2018
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First version publication date |
12 Jul 2018
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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 |
CNVA237A3401
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01959516 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
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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 |
27 Oct 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Oct 2014
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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 |
The primary objective was to demonstrate that glycopyrronium QD is superior to
tiotropium QD in terms of FEV1 AUC0-4h after first dose of treatment.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Feb 2014
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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: 69
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Country: Number of subjects enrolled |
Italy: 8
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Country: Number of subjects enrolled |
Spain: 11
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Country: Number of subjects enrolled |
United Kingdom: 38
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Worldwide total number of subjects |
126
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EEA total number of subjects |
126
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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) |
55
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From 65 to 84 years |
71
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 126 patients were randomized to one of the two treatment sequences in a ratio of 1:1. Due to misrandomization, two patients did not receive at least one dose of the study treatment. Both, safety and ITT population included 124 patients. | |||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Epoch 1
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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 | |||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Glycopyrronium first, then Tiotropium | |||||||||||||||||||||||||||||||||||||||
Arm description |
Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium) Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Seebri® SDDPI / Glycopyrronium bromide
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Investigational medicinal product code |
CNVA237A
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Inhalation use
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Dosage and administration details |
capsule for inhalation
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Arm title
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Tiotropium first, then Glycopyrronium | |||||||||||||||||||||||||||||||||||||||
Arm description |
Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD + placebo of tiotropiumto) Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium) | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Seebri® SDDPI / Glycopyrronium bromide
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Investigational medicinal product code |
CNVA237A
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Inhalation use
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Dosage and administration details |
capsule for inhalation
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Period 2
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Period 2 title |
Epoch 2
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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 | |||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Glycopyrronium first, then Tiotropium\" | |||||||||||||||||||||||||||||||||||||||
Arm description |
Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium) Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Seebri® SDDPI / Glycopyrronium bromide
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Investigational medicinal product code |
CNVA237A
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Inhalation use
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Dosage and administration details |
capsule for inhalation
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Arm title
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Tiotropium first, then Glycopyrronium | |||||||||||||||||||||||||||||||||||||||
Arm description |
Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD + placebo of tiotropiumto) Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium) | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Seebri® SDDPI / Glycopyrronium bromide
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Investigational medicinal product code |
CNVA237A
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Inhalation use
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Dosage and administration details |
capsule for inhalation
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Baseline characteristics reporting groups
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Reporting group title |
Epoch 1
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
All participants (Intent To Treat analysis,ITT)
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All participants who were randomized to one of the two treatment sequences in a ratio of 1:1. Participants will receive sequence A = glycopyrronium + placebo to tiotropium during 28 days, followed by a 14 day washout period, then sequence B= tiotropium + placebo to glycopyrronium for 28 days.
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Subject analysis set title |
Glycopyronium from sequence A to B and sequence B to A
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium) Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto)
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Subject analysis set title |
Tiotropium from sequence A to B and sequence B to A
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD + placebo of tiotropiumto)Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium)
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End points reporting groups
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Reporting group title |
Glycopyrronium first, then Tiotropium
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Reporting group description |
Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium) Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) | ||
Reporting group title |
Tiotropium first, then Glycopyrronium
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Reporting group description |
Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD + placebo of tiotropiumto) Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium) | ||
Reporting group title |
Glycopyrronium first, then Tiotropium\"
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Reporting group description |
Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium) Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) | ||
Reporting group title |
Tiotropium first, then Glycopyrronium
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Reporting group description |
Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD + placebo of tiotropiumto) Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium) | ||
Subject analysis set title |
All participants (Intent To Treat analysis,ITT)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All participants who were randomized to one of the two treatment sequences in a ratio of 1:1. Participants will receive sequence A = glycopyrronium + placebo to tiotropium during 28 days, followed by a 14 day washout period, then sequence B= tiotropium + placebo to glycopyrronium for 28 days.
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Subject analysis set title |
Glycopyronium from sequence A to B and sequence B to A
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium) Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto)
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Subject analysis set title |
Tiotropium from sequence A to B and sequence B to A
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Sequence B (Tiotropium 18 μg QD + placebo of glycopyrronium) to A (Glycopyrronium 44 μg QD + placebo of tiotropiumto)Sequence A (Glycopyrronium 44 μg QD+ placebo of tiotropiumto) to B (Tiotropium 18 μg QD + placebo of glycopyrronium)
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End point title |
Forced Expiratory Volume in 1 second (FEV1) AUC0-4h after first dose of treatment. | ||||||||||||
End point description |
Forced Expiratory Volume in 1 second (FEV1) Area Under the Curve (AUC) will measured via spirometry and calculated from 0 to 4 hours post-dose on day 1 of study treatment.
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End point type |
Primary
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End point timeframe |
Day 1
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Statistical analysis title |
Forced Expiratory Volume in 1 second | ||||||||||||
Comparison groups |
Glycopyronium from sequence A to B and sequence B to A v Tiotropium from sequence A to B and sequence B to A
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Number of subjects included in analysis |
248
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.025 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Comparison of glycopyrronium QD versus tiotropium QD on symptoms outcome | ||||||||||||||||||
End point description |
Comparison of symptoms outcome between glycopyrronium QD versus tiotropium QD will be conducted via the PROMorning COPD Symptoms questionnaire. This questionnaire will be completed by participants at waking-up, pre-inhalation of study treatment (at home), and they will complete Part 2 of PRO-Morning COPD Symptoms questionnaire at site, 3hours post-inhalation of study treatment. The PRO-Morning COPD Symptoms Questionnaire is a self-administered patient reported outcome (PRO) instrument developed by the sponsor to evaluate patients' experience of early morning symptoms of COPD. The questionnaire consists of two parts : predose and postdose. Each part has 6 questions and for each question a scale of 0 to 10 can be reached. For the predose and postdose part of the questionnaire you will have then each a total score of 0-60 by adding the sub-scores for each question, higher scores represent worse severity of COPD morning symptoms
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End point type |
Secondary
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End point timeframe |
day 1 (baseline) and week 4
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Statistical analysis title |
Comparison of glycopyrronium versus tiotropium | ||||||||||||||||||
Comparison groups |
Glycopyronium from sequence A to B and sequence B to A v Tiotropium from sequence A to B and sequence B to A
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Number of subjects included in analysis |
248
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.1439 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Timeframe for AE
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Adverse event reporting additional description |
AE additional description
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Tiotropium
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Reporting group description |
Tiotropium | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Glycopyrronium
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Reporting group description |
Glycopyrronium | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: AEs are validated |
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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? 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. | |||
Due to EudraCT system limitations, which EMA is aware of, results of crossover studies are not accurately represented in this record. Please go to https://www.novctrd.com/CtrdWeb/home.nov for complete trial results. |