Clinical Trials Register

Summary
EudraCT Number:	2012-003791-40
Sponsor's Protocol Code Number:	PSX100201
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:	2012-10-09
Trial 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

2012-003791-40

A.3

Full title of the trial

An Investigation of the Efficacy, Tolerability and Safety of a Range of Doses of Orally Inhaled Glycopyrronium Bromide (PSX1002-GB pMDI) in Male and Female Patients with Moderate or Severe Chronic Obstructive Pulmonary Disease

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Dose ranging study of glycopyrronium bromide in moderate/severe COPD

A.3.2

Name or abbreviated title of the trial where available

Dose ranging study of glycopyrronium bromide in moderate/severe COPD

A.4.1

Sponsor's protocol code number

PSX100201

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Prosonix Limited
B.1.3.4	Country	United Kingdom
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	Prosonix Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Prosonix Limited
B.5.2	Functional name of contact point	Chief Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	The Magdalen Centre, Oxford Science Park
B.5.3.2	Town/ city	Oxford
B.5.3.3	Post code	OX4 4GA
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01865784244
B.5.5	Fax number	01865784251
B.5.6	E-mail	geoff.down@prosonix.co.uk

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	PSX1002-GB pMDI
D.3.2	Product code	PSX1002-GB pMDI
D.3.4	Pharmaceutical form	Pressurised inhalation, suspension
D.3.4.1	Specific paediatric formulation	No
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	glycopyrronium bromide
D.3.9.1	CAS number	596-51-0
D.3.9.2	Current sponsor code	PSX1002
D.3.9.3	Other descriptive name	glycopyrrolate
D.3.9.4	EV Substance Code	AS1
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	glycopyrronium bromide
D.3.9.1	CAS number	596-51-0
D.3.9.2	Current sponsor code	PSX1002
D.3.9.3	Other descriptive name	glycopyrrolate
D.3.9.4	EV Substance Code	AS4
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	50
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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, suspension
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

Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD)

E.1.1.1

Medical condition in easily understood language

Chronic bronchitis and/or emphysema.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10009033
E.1.2	Term	Chronic obstructive pulmonary disease
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To establish the dose-response characteristics of PSX1002-GB pMDI over 24 hours as demonstrated by changes in forced expiratory volume in one second (FEV1)

E.2.2

Secondary objectives of the trial

To establish the dose-response characteristics of PSX1002-GB pMDI over 24 hours as demonstrated by change in forced vital capacity (FVC).
To establish the pharmacokinetic (PK) profile of PSX1002-GB pMDI over 24 hours.
To assess the safety and tolerability of PSX1002-GB pMDI.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female age 40-75 years, inclusive
2. A clinical diagnosis of moderate to severe COPD according to the GOLD guidelines
3. Current smokers or ex-smokers with at least 10-pack year smoking history (e.g., at least one pack/day for 10 years, or 10 packs/day for one year
4. Post-bronchodilator FEV1/FVC ratio < 70 % at Screen
5. Post-bronchodilator FEV1 ≥ 40 % to < 80 % of predicted at Screen
6. Demonstrated to be responsive to ipratropium (defined as at least an 100ml increase in FEV1 following ipratopium 80 μg)
7. Ability to perform acceptable spirometry according to the ATS/ERS guidelines
8. Willing and able to provide written informed consent

E.4

Principal exclusion criteria

1. Females who are pregnant or lactating at the Screening Visit, or if of childbearing potential not using one of the following acceptable means of birth control throughout the study:
a. Established use of oral, injected or implanted hormonal methods of contraception (for at least one month prior to the Screening Visit)
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS).
c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
d. True abstinence when this is in line with the subject’s preferred and usual lifestyle. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not considered acceptable methods of contraception).
e. Bilateral tubal ligation
Females are considered to be of childbearing potential unless either:
a. Permanently sterilised (e.g. bilateral salpingectomy, bilateral oophorectomy or hysterectomy) or;
b. Postmenopausal (i.e. spontaneous amenorrhoea for at least 2 years)
2. Current evidence or recent history of any clinically significant disease (other than COPD) or abnormality in the opinion of the Investigator that would put the subject at risk or which would compromise the quality of the study data; including but not limited to cardiovascular disease, myocardial infarction, cardiac failure, uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes, neurologic or neuromuscular disease, liver disease, gastrointestinal disease or electrolyte abnormalities
3. Recent history of hospitalisation due to an exacerbation of airway disease within three months prior to the Screening Visit or randomisation
4. Need for increased treatments of COPD within six weeks prior to the Screening Visit or randomisation
5. Primary diagnosis of asthma
6. Prior lung volume reductions surgery or history of chest/lung irradiation
7. Regular use of daily oxygen therapy
8. Use of systemic steroids within three months prior to the Screening Visit or during the run-in period
9. Respiratory tract infection within six weeks prior to the Screening Visit. Respiratory tract infections acquired during the run-in period will be assessed by the Investigator to determine suitability to continue in the study.
10. History of tuberculosis, bronchiectasis or other non-specific pulmonary disease
11. History of urinary retention or bladder neck obstructive type symptoms
12. History of narrow-angle glaucoma
13. Clinically significant abnormal ECG
14. Positive Hepatitis B antigen or positive Hepatitis C antibody
15. Positive screening test for HIV antibodies
16. Current evidence or history of excessive use or abuse of alcohol in the opinion of the Investigator
17. Current evidence or history of abusing legal drugs or use of illegal drugs or substances in the opinion of the Investigator
18. Donation of 450 ml or more of blood within eight weeks of the Screening Visit
19. History of hypersensitivity or intolerance to aerosol medications
20. Participation in another investigational drug study where drug was received within 30 days prior to the Screening Visit.
21. Inability to comply with study procedures or with study treatment intake, including inability to be trained and/or inability to demonstrate good inhaler technique with Vitalograph AIM®

E.5 End points

E.5.1

Primary end point(s)

To establish the dose-response characteristics of PSX1002-GB pMDI over 24 hours as demonstrated by changes in forced expiratory volumes in one second (FEV1)

The primary efficacy endpoint will be FEV1 time-adjusted AUC(0-24 hours).

E.5.1.1

Timepoint(s) of evaluation of this end point

Spirometry (FEV1): pre-dose, 5 and 15, 30 minutes and 1, 2, 4, 6, 8, 10, 12, 14, 20, 22, 24, and 26 hours post-dose.

E.5.2

Secondary end point(s)

Secondary efficacy endpoints are FEV1 time-adjusted AUC(0-12 hours), FEV1 time-adjusted AUC(12-24 hours) and serial FEV1 time-points.
FVC will be analysed as described for FEV1.
FEV1/FVC will be analysed using descriptive statistics.
Safety:
The safety parameters that will be evaluated include spontaneous adverse events, clinical examination findings, serial pulmonary flow measures, serial electrocardiogram, and clinical laboratory findings.
Pharmacokinetics:
The PK parameters to be evaluated for plasma glycopyrronium bromide are maximum concentration (Cmax), time to maximum concentration (Tmax), terminal elimination half-life (T1/2), area under the plasma concentration-time curve from time = 0 to time of last measurable drug concentration (AUC0-t), area under the plasma concentration-time curve from time = 0 to infinity (AUC0-inf, total plasma clearance after extravascular administration (CL/F) and apparent volume of distribution after extravascular administration (Vz/F).

E.5.2.1

Timepoint(s) of evaluation of this end point

Spirometry (FVC): pre-dose, 5 and 15, 30 minutes and 1, 2, 4, 6, 8, 10, 12, 14, 20, 22, 24, and 26 hours post-dose.
Pharmacokinetic samples will be obtained at 30 minutes prior to dosing, 5, 15, 30 minutes and 1, 2, 4, 8, 12, and 24 hour post-dose.
Vital signs and 12-lead electrocardiogram will be obtained at pre-dose and 30 minutes, 1, 2, 4, 6, 12 and 24 hour post-dose.
Clinical labs will be obtained at Screening Visit and 7-14 days after the last study treatment (Safety Follow-up Visit).

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

Yes

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

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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.8.5

The trial involves multiple Member States

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

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

LVLS

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1