Trial Outcomes & Findings for Effect of Glycopyrronium on Morning Symptoms and Pulmonary Function in Patients With Moderate to Severe COPD (NCT NCT01959516)
NCT ID: NCT01959516
Last Updated: 2016-04-15
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
124 participants
Primary outcome timeframe
Day 1
Results posted on
2016-04-15
Participant Flow
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.
Participant milestones
| Measure |
Glycopyrronium First, Then Tiotropium"
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)
|
Tiotropium First, Then Glycopyrronium
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)
|
|---|---|---|
|
Epoch 1
STARTED
|
63
|
63
|
|
Epoch 1
Safety Population
|
62
|
62
|
|
Epoch 1
ITT Population
|
62
|
62
|
|
Epoch 1
COMPLETED
|
53
|
58
|
|
Epoch 1
NOT COMPLETED
|
10
|
5
|
|
Epoch 2
STARTED
|
63
|
63
|
|
Epoch 2
COMPLETED
|
61
|
62
|
|
Epoch 2
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Glycopyrronium First, Then Tiotropium"
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)
|
Tiotropium First, Then Glycopyrronium
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)
|
|---|---|---|
|
Epoch 1
Adverse Event
|
4
|
1
|
|
Epoch 1
unsatisfactory therapeutic effect
|
1
|
0
|
|
Epoch 1
Subject withdrew consent
|
3
|
2
|
|
Epoch 1
Administrative problems
|
1
|
0
|
|
Epoch 1
Use of prohibited treatment
|
1
|
0
|
|
Epoch 1
Moderate or severe COPD exacerbation
|
0
|
1
|
|
Epoch 1
Protocol deviation
|
0
|
1
|
|
Epoch 2
unsatisfactory therapeutic effect
|
1
|
0
|
|
Epoch 2
Subject withdrew consent
|
1
|
0
|
|
Epoch 2
Moderate or severe COPD exacerbation
|
0
|
1
|
Baseline Characteristics
Effect of Glycopyrronium on Morning Symptoms and Pulmonary Function in Patients With Moderate to Severe COPD
Baseline characteristics by cohort
| Measure |
All Participants (Intent To Treat Analysis,ITT)
n=124 Participants
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.
|
|---|---|
|
Age, Continuous
|
65.7 Years
STANDARD_DEVIATION 8.1 • n=99 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
87 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Day 1Population: 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
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.
Outcome measures
| Measure |
Glycopyronium From Sequence A to B and Sequence B to A
n=124 Participants
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)
|
Tiotropium From Sequence A to B and Sequence B to A
n=124 Participants
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)
|
|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) AUC0-4h After First Dose of Treatment.
|
1.7432 Liters*hours
95% Confidence Interval 0.5171 • Interval 1.7132 to 1.7732
|
1.7132 Liters*hours
95% Confidence Interval 0.5175 • Interval 1.683 to 1.7434
|
SECONDARY outcome
Timeframe: day 1 (baseline) and week 4Population: 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
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
Outcome measures
| Measure |
Glycopyronium From Sequence A to B and Sequence B to A
n=124 Participants
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)
|
Tiotropium From Sequence A to B and Sequence B to A
n=124 Participants
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)
|
|---|---|---|
|
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 • Interval 8.7294 to 10.6841
|
10.3974 Scores on a scale
95% Confidence Interval 8.1 • Interval 9.4036 to 11.3913
|
|
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 • Interval 9.3786 to 11.5496
|
10.3193 Scores on a scale
95% Confidence Interval 9.3 • Interval 9.2286 to 11.41
|
Adverse Events
Glycopyronium From Sequence A to B and Sequence B to A
Serious events: 2 serious events
Other events: 17 other events
Deaths: 0 deaths
Tiotropium From Sequence A to B and Sequence B to A
Serious events: 2 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Glycopyronium From Sequence A to B and Sequence B to A
n=124 participants at risk
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)
|
Tiotropium From Sequence A to B and Sequence B to A
n=124 participants at risk
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)
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.81%
1/124
|
0.00%
0/124
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.00%
0/124
|
0.81%
1/124
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.81%
1/124
|
0.00%
0/124
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/124
|
0.81%
1/124
|
Other adverse events
| Measure |
Glycopyronium From Sequence A to B and Sequence B to A
n=124 participants at risk
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)
|
Tiotropium From Sequence A to B and Sequence B to A
n=124 participants at risk
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)
|
|---|---|---|
|
Cardiac disorders
Bundle branch block left
|
0.81%
1/124
|
0.00%
0/124
|
|
Cardiac disorders
Bundle branch block right
|
0.81%
1/124
|
0.00%
0/124
|
|
Eye disorders
Cystoid macular oedema
|
0.81%
1/124
|
0.00%
0/124
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/124
|
0.81%
1/124
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/124
|
0.81%
1/124
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/124
|
0.81%
1/124
|
|
General disorders
Chest pain
|
0.00%
0/124
|
0.81%
1/124
|
|
General disorders
Oedema peripheral
|
0.00%
0/124
|
0.81%
1/124
|
|
Hepatobiliary disorders
Hepatic cyst
|
0.00%
0/124
|
0.81%
1/124
|
|
Immune system disorders
Food allergy
|
0.81%
1/124
|
0.00%
0/124
|
|
Infections and infestations
Dermatophytosis
|
0.81%
1/124
|
0.00%
0/124
|
|
Infections and infestations
Infected dermal cyst
|
0.00%
0/124
|
0.81%
1/124
|
|
Infections and infestations
Lower respiratory tract infection
|
0.81%
1/124
|
0.81%
1/124
|
|
Infections and infestations
Nasopharyngitis
|
2.4%
3/124
|
0.00%
0/124
|
|
Infections and infestations
Respiratory tract infection
|
0.81%
1/124
|
0.00%
0/124
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.81%
1/124
|
0.00%
0/124
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
0.00%
0/124
|
0.81%
1/124
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.81%
1/124
|
0.00%
0/124
|
|
Musculoskeletal and connective tissue disorders
Ankylosing spondylitis
|
0.81%
1/124
|
0.00%
0/124
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.81%
1/124
|
0.81%
1/124
|
|
Musculoskeletal and connective tissue disorders
Limb discomfort
|
0.00%
0/124
|
0.81%
1/124
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.81%
1/124
|
0.00%
0/124
|
|
Nervous system disorders
Headache
|
0.81%
1/124
|
0.81%
1/124
|
|
Nervous system disorders
Presyncope
|
0.81%
1/124
|
0.81%
1/124
|
|
Nervous system disorders
Sciatica
|
0.81%
1/124
|
0.00%
0/124
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/124
|
0.81%
1/124
|
|
Reproductive system and breast disorders
Balanoposthitis
|
0.00%
0/124
|
0.81%
1/124
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.6%
2/124
|
0.00%
0/124
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/124
|
0.81%
1/124
|
|
Respiratory, thoracic and mediastinal disorders
Sputum discoloured
|
0.81%
1/124
|
0.00%
0/124
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.81%
1/124
|
0.81%
1/124
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.81%
1/124
|
0.00%
0/124
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/124
|
0.81%
1/124
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
- Publication restrictions are in place
Restriction type: OTHER