COPD
Conditions
Keywords
COPD, early morning symptoms
Brief 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.
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.
Interventions
DRUGGlycopyrronium
Glycopyrronium capsule for inhalation once per day via SDDPI
DRUGTiotropium
Tiotropium capsule for inhalation once per day via HandiHaler® device
DRUGPlacebo to glycopyrronium
Placebo to glycopyrronium capsule for inhalation once per day via SDDPI
Placebo to tiotropium capsule for inhalation once per day via HandiHaler® device
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) AUC0-4h After First Dose of Treatment. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Glycopyrronium QD Versus Tiotropium QD on Symptoms Outcome | day 1 (baseline) and week 4 | 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 |
Countries
Germany, Italy, Spain, United Kingdom
Participant flow
Recruitment 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.
Participants by arm
| Arm | Count |
|---|---|
| All Participants (Intent To Treat Analysis,ITT) 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. | 124 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Epoch 1 | Administrative problems | 1 | 0 |
| Epoch 1 | Adverse Event | 4 | 1 |
| Epoch 1 | Moderate or severe COPD exacerbation | 0 | 1 |
| Epoch 1 | Protocol deviation | 0 | 1 |
| Epoch 1 | Subject withdrew consent | 3 | 2 |
| Epoch 1 | unsatisfactory therapeutic effect | 1 | 0 |
| Epoch 1 | Use of prohibited treatment | 1 | 0 |
| Epoch 2 | Moderate or severe COPD exacerbation | 0 | 1 |
| Epoch 2 | Subject withdrew consent | 1 | 0 |
| Epoch 2 | unsatisfactory therapeutic effect | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants (Intent To Treat Analysis,ITT) |
|---|---|
| Age, Continuous | 65.7 Years STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 124 | 12 / 124 |
| serious Total, serious adverse events | 2 / 124 | 2 / 124 |
Outcome results
Primary
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.
Time frame: Day 1
Population: 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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Glycopyronium From Sequence A to B and Sequence B to A | Forced Expiratory Volume in 1 Second (FEV1) AUC0-4h After First Dose of Treatment. | 1.7432 Liters*hours | 95% Confidence Interval 0.5171 |
| Tiotropium From Sequence A to B and Sequence B to A | Forced Expiratory Volume in 1 Second (FEV1) AUC0-4h After First Dose of Treatment. | 1.7132 Liters*hours | 95% Confidence Interval 0.5175 |
p-value: 0.025Mixed Models Analysis
Secondary
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
Time frame: day 1 (baseline) and week 4
Population: 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
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Glycopyronium From Sequence A to B and Sequence B to A | Comparison of Glycopyrronium QD Versus Tiotropium QD on Symptoms Outcome | 3h post-dose (Day 1) | 9.7068 Scores on a scale | 95% Confidence Interval 8.8 |
| Glycopyronium From Sequence A to B and Sequence B to A | Comparison of Glycopyrronium QD Versus Tiotropium QD on Symptoms Outcome | 3h post-dose (Week 4) | 10.4641 Scores on a scale | 95% Confidence Interval 8.8 |
| Tiotropium From Sequence A to B and Sequence B to A | Comparison of Glycopyrronium QD Versus Tiotropium QD on Symptoms Outcome | 3h post-dose (Day 1) | 10.3974 Scores on a scale | 95% Confidence Interval 8.1 |
| Tiotropium From Sequence A to B and Sequence B to A | Comparison of Glycopyrronium QD Versus Tiotropium QD on Symptoms Outcome | 3h post-dose (Week 4) | 10.3193 Scores on a scale | 95% Confidence Interval 9.3 |
p-value: 0.1439Mixed Models Analysis