COPDPhase 4NCT01959516

Effect of Glycopyrronium on Morning Symptoms and Pulmonary Function in Patients With Moderate to Severe COPD

A Phase 4 study testing Glycopyrronium and Tiotropium in people with COPD, run by Novartis Pharmaceuticals at 21 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This study purpose is to further study the profiles of glycopyrronium (NVA237) and tiotropium during the first hours after dosing and their impact on pulmonary function, COPD symptoms and ability to perform daily activities by the patient. Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: COPD
What is being tested?: Glycopyrronium and Tiotropium
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 124 participants
Where: 21 sitesin 4 countries
Study dates: Feb 2014to Oct 2014
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female adults aged ≥ 40 years.
Co-operative outpatients with a clinical diagnosis of moderate to severe COPD confirmed by spirometry according to GOLD criteria 2013 and including all of the following: a) Current or ex-smokers who have a smoking history of at least 10 pack years (e.g.10 pack years = 1 pack /day x 10 years or ½ pack/day x 20 years). An ex-smoker may be defined as a subject who has not smoked for ≥ 6 months at Screening. b) Patients with airflow limitation indicated by a post-bronchodilator FEV1 < 80% and ≥ 40% of the predicted normal value at Visit 2 (Post- bronchodilator refers to within 10-15 min of inhalation of 400 µg (4x100 µg) of salbutamol). c) .Post-bronchodilator FEV1/FVC < 0.7 at Visit 2 (Post- bronchodilator refers to within 10-15 min of inhalation of 400 µg (4x100 µg) of salbutamol).
Patients with a COPD Assessment Test (CAT) score ≥ 10 at Visit 2.

Who cannot join

Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment or antibiotics and/or hospitalization in the 6 weeks prior to Visit 1. In the event of an exacerbation occurring during the Screening period (Visits 1-2), the patient must be discontinued from the study. The patient may be re-enrolled once the inclusion/exclusion criteria are met. Only one re-enrollment is allowed.
Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1. Patients who develop a respiratory tract infection between Visit 1 and Visit 2 must discontinue from the trial, but may be permitted to re-enrol at a later date once the inclusion/exclusion criteria have been met. Only one re-enrollment is allowed.
Patients on any long-acting bronchodilator therapy. Those patients may enter the study after bronchodilator withdrawal during a 10-day wash-out period (only rescue salbutamol allowed as bronchodilator therapy during wash-out). Patients on fixed combination of long acting β2-agonists/inhaled corticosteroid (LABA/ICS) therapy before screening must be switched to the equivalent dose of ICS monotherapy and salbutamol as rescue.
Patients receiving any other prohibited COPD-related medications specified in Table 5-1 must undergo the required wash-out period prior to Visit 2.
Patients who have had a clinical history of asthma.
Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis or clinically significant bronchiectasis.

Show all 14Show fewer

Patients with alpha-1-antitrypsin deficiency.
Patients with contraindications for LAMA treatment including medical history of symptomatic prostatic hypertrophy, bladder neck obstruction, narrow-angle glaucoma and severe renal impairment (estimated glomerular filtration rate below 30 ml/min/1.73 m2) documented in the previous 6 months.
Patients with a history of unstable cardiovascular disease or arrhythmias including atrial fibrillation/flutter or long QT syndrome or whose resting QTcF (calculated according to Fridericia QT correction formula preferred, but Bazett acceptable) is prolonged (≥ 450 msec for males and ≥ 460 msec for females) at screening (Visit 1) or baseline (Visit 2, baseline 1).
Concomitant use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study.
Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof: -anticholinergic agents - long and short acting 2 agonists -sympathomimetic amines -excipients of the trial medication (lactose monohydrate and/or magnesium estearate)
Patients whose body mass index (BMI) is less than 15 or greater than 40 kg/m2.
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
Other exclusion criteria may apply

Trial locations and contacts

21 sites in 4 countries.

Country

City, postcode or hospital

21 sites in 4 countries

Germany9 sites

Novartis Investigative Site
Berlin, Germany, 12099
Novartis Investigative Site
Berlin, State of Berlin, 10119
Novartis Investigative Site
Berlin, 13156
Novartis Investigative Site
Geesthacht, Schleswig-Holstein, 12502
Novartis Investigative Site
Halle, 06108
Novartis Investigative Site
Leipzig, 04103
Novartis Investigative Site
Leipzig, 04275
Novartis Investigative Site
Potsdam, Germany, 14467
Novartis Investigative Site
Wiesbaden, Germany, 65187

Other trials in Germany

United Kingdom6 sites

Novartis Investigative Site
Blackpool, FY3 7EN
Novartis Investigative Site
Bradford, BD9 6RJ
Novartis Investigative Site
Cambridge, United KIngdom, CB7 5JD
Novartis Investigative Site
Cardiff, CF5 4AD
Novartis Investigative Site
Watford, United Kingdom, WD25 7NL
Novartis Investigative Site
Wishaw, ML2 0DP

Other trials in United Kingdom

Italy3 sites

Novartis Investigative Site
Florence, FI, 50122
Novartis Investigative Site
Milan, MI, 20138
Novartis Investigative Site
Orbassano, TO, 10043

Other trials in Italy

Spain3 sites

Novartis Investigative Site
Barcelona, Catalonia, 08026
Novartis Investigative Site
Lugo, Galicia, 27003
Novartis Investigative Site
Zaragoza, Zaragoza, 50009

Other trials in Spain

About this study

Official title: 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

Read the detailed description

Randomized, multicenter, blinded, two-period cross-over design. Each treatment will last 28 days. All patients will receive both treatments in a cross-over design, with a wash-out period of 14-19 days in between. The total duration of the study for each patient is approximately 70 days (from randomization) plus 30 days of safety follow-up.

Conditions: COPD
Being tested: Glycopyrronium, Tiotropium, Placebo to glycopyrronium, Placebo to tiotropium
Keywords: COPD, early morning symptoms
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GlycopyrroniumDrug
Glycopyrronium capsule for inhalation once per day via SDDPI
TiotropiumDrug
Tiotropium capsule for inhalation once per day via HandiHaler® device
Placebo to glycopyrroniumDrug
Placebo to glycopyrronium capsule for inhalation once per day via SDDPI
Placebo to tiotropiumDrug
Placebo to tiotropium capsule for inhalation once per day via HandiHaler® device

Study groups in NCT01959516
Study group	Role	What they receive
Sequence A ⇒ B	Experimental	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. Receives: Drug: Glycopyrronium; Drug: Tiotropium; Drug: Placebo to glycopyrronium; Drug: Placebo to tiotropium
Sequence B ⇒ A	Experimental	Participants will receive sequence B= tiotropium + placebo to glycopyrronium during 28 days, followed by a 14 day washout period, then sequence A= glycopyrronium + placebo to tiotropium for 28 days. Receives: Drug: Glycopyrronium; Drug: Tiotropium; Drug: Placebo to glycopyrronium; Drug: Placebo to tiotropium

What is being measured

The primary outcome is the main question the study is designed to answer.

Forced Expiratory Volume in 1 Second (FEV1) AUC0-4h After First Dose of Treatment.
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.
Measured: Day 1

Secondary outcomes (1)

Comparison of Glycopyrronium QD Versus Tiotropium QD on Symptoms Outcome
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
Measured: day 1 (baseline) and week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2014Oct 2014

First posted10 Oct 2013 (estimated)
Study startFeb 2014
Primary completionOct 2014
Study completionOct 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for COPDStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 124 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01959516
Sponsor's protocol ID: CNVA237A3401
Status last verified: Mar 2016
First submitted: 8 Oct 2013
Last updated: 15 Apr 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 15 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT01959516
Acronym / sponsor ID: CNVA237A3401
Conditions: COPD
Keywords: COPD, early morning symptoms
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 124 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Feb 2014
Primary completion: Oct 2014 (actual)
Study completion: Oct 2014 (actual)
First posted: 10 Oct 2013 (estimated)
Results: Posted 15 Apr 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Sequence A ⇒ B	Experimental	Drug: Glycopyrronium, Drug: Tiotropium, Drug: Placebo to glycopyrronium, Drug: Placebo to tiotropiumParticipants 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.
Sequence B ⇒ A	Experimental	Drug: Glycopyrronium, Drug: Tiotropium, Drug: Placebo to glycopyrronium, Drug: Placebo to tiotropiumParticipants will receive sequence B= tiotropium + placebo to glycopyrronium during 28 days, followed by a 14 day washout period, then sequence A= glycopyrronium + placebo to tiotropium for 28 days.

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Male and female adults aged ≥ 40 years.
Co-operative outpatients with a clinical diagnosis of moderate to severe COPD confirmed by spirometry according to GOLD criteria 2013 and including all of the following: a) Current or ex-smokers who have a smoking history of at least 10 pack years (e.g.10 pack years = 1 pack /day x 10 years or ½ pack/day x 20 years). An ex-smoker may be defined as a subject who has not smoked for ≥ 6 months at Screening. b) Patients with airflow limitation indicated by a post-bronchodilator FEV1 < 80% and ≥ 40% of the predicted normal value at Visit 2 (Post- bronchodilator refers to within 10-15 min of inhalation of 400 µg (4x100 µg) of salbutamol). c) .Post-bronchodilator FEV1/FVC < 0.7 at Visit 2 (Post- bronchodilator refers to within 10-15 min of inhalation of 400 µg (4x100 µg) of salbutamol).
Patients with a COPD Assessment Test (CAT) score ≥ 10 at Visit 2.

Key exclusion criteria (14 listed)

Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment or antibiotics and/or hospitalization in the 6 weeks prior to Visit 1. In the event of an exacerbation occurring during the Screening period (Visits 1-2), the patient must be discontinued from the study. The patient may be re-enrolled once the inclusion/exclusion criteria are met. Only one re-enrollment is allowed.
Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1. Patients who develop a respiratory tract infection between Visit 1 and Visit 2 must discontinue from the trial, but may be permitted to re-enrol at a later date once the inclusion/exclusion criteria have been met. Only one re-enrollment is allowed.
Patients on any long-acting bronchodilator therapy. Those patients may enter the study after bronchodilator withdrawal during a 10-day wash-out period (only rescue salbutamol allowed as bronchodilator therapy during wash-out). Patients on fixed combination of long acting β2-agonists/inhaled corticosteroid (LABA/ICS) therapy before screening must be switched to the equivalent dose of ICS monotherapy and salbutamol as rescue.
Patients receiving any other prohibited COPD-related medications specified in Table 5-1 must undergo the required wash-out period prior to Visit 2.
Patients who have had a clinical history of asthma.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GlycopyrroniumGlycopyrronium capsule for inhalation once per day via SDDPI	Drug	Sequence A ⇒ B, Sequence B ⇒ A
TiotropiumTiotropium capsule for inhalation once per day via HandiHaler® device	Drug	Sequence A ⇒ B, Sequence B ⇒ A
Placebo to glycopyrroniumPlacebo to glycopyrronium capsule for inhalation once per day via SDDPI	Drug	Sequence A ⇒ B, Sequence B ⇒ A
Placebo to tiotropiumPlacebo to tiotropium capsule for inhalation once per day via HandiHaler® device	Drug	Sequence A ⇒ B, Sequence B ⇒ A

Primary outcome

Forced Expiratory Volume in 1 Second (FEV1) AUC0-4h After First Dose of Treatment.
Time frame: Day 1
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.

1 secondary outcome

Comparison of Glycopyrronium QD Versus Tiotropium QD on Symptoms Outcome
Time frame: day 1 (baseline) and week 4

Results and safety

Results posted to the registry on 15 Apr 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Glycopyrronium First, Then Tiotropium"	63	53
Tiotropium First, Then Glycopyrronium	63	58

Primary outcome: Forced Expiratory Volume in 1 Second (FEV1) AUC0-4h After First Dose of Treatment.

Time frame: Day 1. Least squares mean (95% Confidence Interval). Unit: Liters*hours

Measure	Glycopyronium From Sequence A to B and Sequence B to A n = 124	Tiotropium From Sequence A to B and Sequence B to A n = 124
Value	1.7432 (0.5171)	1.7132 (0.5175)

Glycopyronium From Sequence A to B and Sequence B to A vs Tiotropium From Sequence A to B and Sequence B to A: p = 0.0250, Mixed Models Analysis

Population analysed: The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and had at least one post-dose value of FEV1

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0.5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Glycopyronium From Sequence A to B and Sequence B to A	2 of 124 (1.6%)	17 of 124 (13.7%)	Not reported
Tiotropium From Sequence A to B and Sequence B to A	2 of 124 (1.6%)	12 of 124 (9.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

21 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Glycopyrronium and Tiotropium in people with COPD, run by Novartis Pharmaceuticals at 21 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Germany, United Kingdom, Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Forced Expiratory Volume in 1 Second (FEV1) AUC0-4h After First Dose of Treatment. (time frame: Day 1). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01959516.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2016.