Clinical Trials Register

Summary
EudraCT Number:	2010-018668-18
Sponsor's Protocol Code Number:	CCD-0916-PR-0032
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-06-08
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2010-018668-18

A.3

Full title of the trial

RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSS-OVER STUDY TO INVESTIGATE THE BRONCHODILATOR EFFICACY AND SAFETY AFTER SINGLE AND REPEATED ADMINISTRATIONS OF DIFFERENT DOSES OF GLYCOPYRROLATE VIA PMDI IN MODERATE TO SEVERE COPD PATIENTS.
(GLYCO 2)

A.3.2

Name or abbreviated title of the trial where available

GLY2

A.4.1

Sponsor's protocol code number

CCD-0916-PR-0032

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Chiesi Farmaceutici S.p.A.
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Glyco pMDI
D.3.2	Product code	CHF 5259 pMDI
D.3.4	Pharmaceutical form	Pressurised inhalation, solution
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	glycopyrrolate bromide
D.3.9.1	CAS number	596-51-0
D.3.9.2	Current sponsor code	CHF 5259.02
D.3.9.3	Other descriptive name	Glyco
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	glycopyrrolate bromide
D.3.9.1	CAS number	596-51-0
D.3.9.2	Current sponsor code	CHF 5259.02
D.3.9.3	Other descriptive name	Glyco
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	12.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Spiriva
D.2.1.1.2	Name of the Marketing Authorisation holder	Boehringer Ingelheim Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Spiriva 18 µg inhalation powder, hard capsule
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TIOTROPIUM BROMIDE
D.3.9.1	CAS number	139404481
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	18
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Pressurised inhalation, solution
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

COPD

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10010952
E.1.2	Term	COPD

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

PART I
• To assess the safety and tolerability of single administration of Glyco pMDI at 5 dose levels in patients with moderate to severe COPD

PART II
• To assess the bronchodilator efficacy of Glyco pMDI at 3 dose levels by comparison with placebo in patients with moderate to severe COPD after repeated administration

E.2.2

Secondary objectives of the trial

PART I
• To assess the bronchodilator efficacy of single administration of Glyco pMDI at 5 dose levels by comparison with placebo in patients with moderate to severe COPD.

PART II
• To evaluate the duration of bronchodilation
• To assess the safety and tolerability of repeated doses of Glyco pMDI.
• To evaluate the pharmacokinetic profile after single and repeated administration of Glyco pMDI.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Males and females patients aged 40-75 years;
2. Written informed consent obtained before the first trial related activity.
3. Diagnosis of moderate-severe COPD, according to the GOLD guidelines (2009);
4. Able to understand the study procedures, the risks involved and ability to be trained to use the devices correctly.
5. Body Mass Index (BMI) between 18.0 and 35 kg/m2;
6. Current or ex-smokers with a smoking history of ≥ 10 pack years (e.g. ≥ 20 cigarettes per day for 10 years and 40 cigarettes per day for 5 years);
7. Vital signs (systolic and diastolic blood pressure and heart rate) within the following ranges : 90 ≤ SBP ≤ 160; 50 ≤ DBP ≤90; 50 ≤ HR ≤ 100);
8. Electrocardiogram (ECG) (12 lead) with computerized protocol interpretation considered as normal (120 ms ≤ PR ≤ 200 ms, QRS ≤ 120 ms, QTcF ≤ 450 ms). Minor deviations are acceptable provided that they are not judged clinically significant by the cardiologist;
9. Post bronchodilator FEV1 between 40% and 80% predicted values (40% ≤ FEV1 ≤ 80%), documented at screening visit ;
10. Post bronchodilator FEV1/Forced Vital Capacity (FEV1/FVC) ≤ 0.70 (absolute value) documented at screening visit;
11. Airway reversibility of at least 100 mL within 30 to 45 minutes after inhalation of ipratropium 80 μg (for Part 2: historical reversibility is acceptable for patients who performed Part 1). If the reversibility criteria are not met and if the investigator deems it appropriate, the testing can be repeated once. This requirement must be met after re-testing during run-in period at least 24h prior to randomisation.

E.4

Principal exclusion criteria

History of chronic or seasonal allergy
2. Blood eosinophil count above 0.6 x 10^9/L.
3. Clinically relevant findings on physical examination, laboratory or ECG parameters at screening.
4. Occurrence of one of the following 24-h Holter ECG abnormalities at screening:
a. More than 200 ventricular ectopics in 24 hours.
b. Ventricular tachycardia;
c. Second degree heart block.
d. Sustained cardiac arrhythmias (atrial fibrillation, SVT, complete heart block).
e. Any symptomatic arrhythmia (except isolated extra systoles)
f. Sinus pauses ≥ 2.5 s
5. Significant disease not related to COPD (eg. Myocardial infarction, stroke within the preceding 6 months)
6. Respiratory tract infection (including upper tract) 4 weeks prior to Screening Visit requiring changing treatment
7. Patients requiring oxygen therapy on a daily basis for chronic hypoxemia
8. Patients who have been hospitalized in the previous 6 weeks prior to screening visit
9. Having received an investigational product within the last 8 weeks before the Screening Visit.
10. Inability to comply with study procedures or with study treatment intake, including inability to be trained with Vitalograph AIM.
11. History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which is considered to be clinically significant by the investigator.
12. Intolerance/hypersensitivity or any contra-indication (e.g history of glaucoma) to treatment with M3 Antagonist or any of the excipients contained in the formulations used in the study.
13. History of alcohol or substance abuse that in the opinion of the Investigator may be of clinical significance.
14. Patients who have undergone major surgery in the 12 weeks before the Screening Visit.
15. Patients treated with oral (slow-release included) or parental steroids 8 weeks prior to Screening Visit
16. Patients treated with oral ß2-adrenergics, antihistamines, or theophyllines 1 month prior to Screening Visit or enzyme inducing or inhibiting drugs 2 months before the first administration.
17. Patients treated with tiotropium in the 10 days prior to the Screening Visit.
18. Female patients: pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of the gestation, confirmed by a positive serum human chorionic gonadotrophin laboratory test (> 5 mIU/mL. Serum pregnancy test to be done at Screening for verification). Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or are using an acceptable method of contraception.
Male patients: must be sterile or they or their partner must be willing to use an approved method of contraception from the time of dose administration and until 30 days after the last dose of study. Patients must not donate sperm for 30 days after the last dose of study drug. A reliable method of contraception for male and female subjects (or their partner), depending on the method, can be one or more of the following ones:
a) Surgical sterilization (i.e. bilateral tubal ligation, hysterectomy for females; vasectomy for males)
b) Hormonal contraception (implantable, patch, oral)
c) Double-barrier methods (any double combination of: IUD, male or female condom, diaphragm, sponge, cervical cap, condom, spermicide).
Periodic abstinence (i.e. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study.

E.5 End points

E.5.1

Primary end point(s)

Part I
Adverse Events (AEs) and Adverse Drug Reactions (ADRs), including occurrence of paradoxical bronchospasm;
vital signs: heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP)
12-lead ECG parameters: ventricular heart rate, PR, QRS, QT, QTcB, QTcF;
abnormal findings on 12-lead ECG;
24 h ECG Holter recordings;
clinical chemistry and hematology, urinalysis.

Part II
Core periods: trough FEV1 at 12 h post-dose on Day 7 (before evening administration) defined as the mean of two measurements at 12 h and 12.5 h post-dose.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

tolerability

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

PART I single-dose, PART II repeated dose

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	64
F.4.2	For a multinational trial
F.4.2.1	In the EEA	64
F.4.2.2	In the whole clinical trial	64

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2010-06-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-07-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-08-10

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