Research study to evaluate the effect of different doses of inhaled glycopyrronium bromide via Nexthaler in COPD patients

• Register: EUCTR
• Last refreshed on: 8 May 2017
• Main ID: EUCTR2015-000558-40-HU
• Date of registration: 29/12/2015
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: Research study to evaluate the effect of different doses of inhaled glycopyrronium bromide via Nexthaler in COPD patients
• Scientific title: A multicenter, randomised, double blind, placebo-controlled, incomplete block, 3-way cross-over study to evaluate the efficacy and safety of 4 doses of glycopyrronium bromide DPI in moderate to severe patients with chronic obstructive pulmonary disease (COPD) -
• Date of first enrolment: 23/02/2016
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000558-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: incomplete block, 3-way crossover Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Germany, Hungary

Contacts

• Name: Clinical Project Manager
• Affiliation: Chiesi Farmaceutici S.p.A.

• Name: Clinical Project Manager
• Affiliation: Chiesi Farmaceutici S.p.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients aged = 40 years at screening visit, who have signed an Informed
Consent form prior to initiation of any study-related procedure.
2. Patients with a diagnosis of COPD (according to GOLD guidelines 2015) at least 12
months before screening visit.
3. Current smoker or ex-smoker with a smoking history of at least 10 pack-years defined as
[(number of cigarettes smoked per day) × (number of years of smoking)] / 20.
(If the subjects undergo smoking cessation therapy, it must be completed 3 months prior to
the screening visit. Smoking cessation must be at least 3 months prior the screening. In both
cases the smoking status should not change between the subjects screening visit and subjects last study visit).
4. A post-bronchodilator FEV1 = 40% and =70% of the predicted normal value (measured 30 to 45 minutes after administration of 80 µg ipratropium pMDI) and,
- a post-bronchodilator FEV1/FVC < 0.7 and,
- a change in FEV1 from the pre-bronchodilator value (reversibility) of at least 5% at
screening
If the criterion is not met at screening, the test can be rescheduled once before randomisation.
5. Patients under bronchodilators with long-acting muscarinic antagonist or long-acting
beta-2 agonist (monotherapy or dual therapy), or patients under ICS + LABA or ICS + LAMA for at least 4 weeks prior to screening. (Patients with a FEV1<50% of the predicted value and a history of 1 exacerbation whithin the last 12 months must have been treated with ICS+LABA or ICS+LAMA before screening)
6. Ability and cooperative attitude to understand and to perform required outcome measurements of the protocol (e.g. spirometry manoeuvres) and ability to understand the risks involved.
Ability to be trained to use the DPI inhalers.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
1. Diagnosis of asthma or other respiratory disorders (other than COPD) which may interfere
with data interpretation according to the investigator’s opinion.
2. Patients had a COPD exacerbation or a lower respiratory tract infection within 8 weeks prior to screening, or during the run-in period, that resulted in the use of an antibiotic, or oral or parenteral corticosteroids, or hospitalisation.
3. Patients with a history of = 2 exacerbations within the last 12 months prior to screening
(frequent exacerbators).
4. Patients treated with oral/parenteral ß2-agonists or nebulised bronchodilators or PDE
inhibitors or who received LABA/LAMA/ICS treatment therapy in the 4 weeks prior to
screening and during the run-in period.
5. Patient is on an inhaled corticosteroid that has been initiated, or the effective dose has been changed, within 4 weeks prior to screening or during the run-in period (patients on stable dose of ICS for at least 4 weeks prior to screening are allowed).
6. Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia.
7. Patients with known respiratory disorders other than COPD.
8. Patients with medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic.
9. Patients who have unstable concurrent disease, that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study;
10. Patients who have a concomitant disease of poor prognosis
11. Patients who have clinically significant cardiovascular condition
12. Patients with known atrial fibrillation (AF):
a. Paroxysmal Atrial Fibrillation
b. Persistent: AF episode lasting more than 7 days or requiring termination by
cardioversion, either with drugs or by direct current cardioversion (DCC) within 6 months prior to screening visit.
c. Long standing persistent: continuous atrial fibrillation diagnosed for less than 6 months
and/ or without a rhythm control strategy.
d. Permanent: AF diagnosed for at least 6 months with a resting ventricular rate = 100/min
not controlled with a rate control strategy (i.e., selective ß-blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy).
13. Patients have a clinically significant abnormal 12-lead ECG that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study.
14. Patients whose electrocardiogram 12-lead ECG shows a QTcF>450 ms for males or QTcF > 470 ms for females.
15. Patients with clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study.
16. Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS they are willing to use a highly effective birth control methods such as :
a. Placement of an intrauterine device or intrauterine releasing system
b. Oral, intravaginal, transdermal combined estrogen and progestogen containing hormonal contraception or oral, injectable, implantable progestogen only hormonal
contraception.
c. Bilateral tubal occlusion
d. Partner vasectomy (provided that partner is the sole sexual partner of the WOCBP
tria

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 18.1 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Glycopyrronium bromide 25µg NEXThaler
Product Code: CHF 5259
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Current Sponsor code: CHF5259.02
Other descriptive name: Glycopyrrolate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Product Name: Glycopyrronium bromide 12.5µg NEXThaler
Product Code: CHF 5259
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Current Sponsor code: CHF5259.02
Other descriptive name: glycopyrrolate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Product Name: Glycopyrronium bromide 6.25µg NEXThaler
Product Code: CHF 5259
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Current Sponsor code: CHF5259.02
Other descriptive name: glycopyrrolate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 6.25-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): FEV1 AUC 0-12h normalised by time

Timepoint(s) of evaluation of this end point: Day 28

Secondary Objective: To evaluate the effect of CHF 5259 glycopyrronium bromide (GB) on lung function parameters.
To assess the safety of the study treatments.

Main Objective: The primary objective is to identify the optimal dose of CHF 5259 glycopyrronium bromide (GB) to be further developed for the treatment of patients with COPD.

Secondary Outcome(s)

Secondary end point(s): EFFICACY VARIABLES:
FEV1, FVC, Transition Dyspnoea Index (TDI)

SAFETY VARIABLES:
Adverse events and adverse drug reactions
Vital signs, ECG and laboratory

Timepoint(s) of evaluation of this end point: Day 1, day 14 and/or day 28, and across the study for safety variables

Secondary ID(s)

CCD-06302AA1-01

2015-000558-40-DE

Source(s) of Monetary Support

Chiesi Farmaceutici S.p.A.