Clinical Trials Register

Summary
EudraCT Number:	2013-002966-38
Sponsor's Protocol Code Number:	CCD-01535BC1-02
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:	2013-09-20
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

2013-002966-38

A.3

Full title of the trial

A PHASE II, PARTIAL-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, 5-WAY CROSS-OVER CLINICAL PHARMACOLOGY STUDY TO EVALUATE THE PHARMACODYNAMICS OF BDP/B17MP AND FORMOTEROL ACROSS TWO DIFFERENT DOSE LEVELS OF CHF 1535 NEXThaler® DPI AND CHF 1535 pMDI (BOTH FIXED COMBINATION OF BECLOMETHASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE) IN ADULT COPD PATIENTS.

A.3.1

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

A study to evaluate the effects of two different doses given once of the combination of two components (beclomethasone plus formoterol) given in two different inhalation formulations to patients with chronic obstructive pulmonary disease.

A.4.1

Sponsor's protocol code number

CCD-01535BC1-02

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	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	Chiesi Farmaceutici S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Chiesi Farmaceutici S.p.A.
B.5.2	Functional name of contact point	Giorgia Ciurlia
B.5.3	Address:
B.5.3.1	Street Address	Via Palermo 26/A
B.5.3.2	Town/ city	Parma
B.5.3.3	Post code	43122
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390521 279 817
B.5.6	E-mail	g.ciurlia@chiesi.com

D. IMP Identification
D.IMP: 1
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	Foster®
D.2.1.1.2	Name of the Marketing Authorisation holder	Chiesi Farmaceutici S.p.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	Pharmaceutical form	Pressurised inhalation, solution
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	BECLOMETASONE DIPROPIONATE
D.3.9.1	CAS number	5534-09-8
D.3.9.3	Other descriptive name	BDP
D.3.9.4	EV Substance Code	SUB00681MIG
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	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FORMOTEROL FUMARATE DIHYDRATE
D.3.9.1	CAS number	43229-80-7
D.3.9.3	Other descriptive name	FF
D.3.9.4	EV Substance Code	SUB25660
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	6
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.IMP: 2
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	Yes
D.2.1.1.1	Trade name	Foster® NEXThaler®
D.2.1.1.2	Name of the Marketing Authorisation holder	Chiesi GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	Pharmaceutical form	Inhalation powder
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	beclometasone dipropionate
D.3.9.1	CAS number	5534-09-8
D.3.9.3	Other descriptive name	BDP
D.3.9.4	EV Substance Code	SUB00681MIG
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	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	formoterol fumarate
D.3.9.1	CAS number	43229-80-7
D.3.9.3	Other descriptive name	FF
D.3.9.4	EV Substance Code	SUB02257MIG
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	6
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, solution
D.8.4	Route of administration of the placebo	Inhalation use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation powder
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 patients

E.1.1.1

Medical condition in easily understood language

difficulty breathing

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	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10010952
E.1.2	Term	COPD
E.1.2	System Organ Class	100000004855

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 compare the average heart rate over 4 hours after administration of BDP and Formoterol using CHF 1535 100/6 NEXThaler® DPI and CHF 1535 100/6 pMDI at two different dose levels

E.2.2

Secondary objectives of the trial

• To evaluate the effects of both formulations on serum potassium and serum glucose and cardiovascular parameters
• To assess the safety and the tolerability of the study treatments

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female adults (≥ 40 and ≤ 75 years old).
2. Female subjects must either be of non-childbearing potential, using at least one acceptable method of contraception or sexually abstinent, from screening until the end of the study.
3. Written informed consent obtained by the patient prior to any study-related procedures.
4. Outpatients with diagnosis of moderate/severe stable COPD, according to GOLD guidelines update 2013 at least in the 6 months before the screening visit.
5. A post-bronchodilator FEV1 ≥ 40 and < 80% of the predicted normal value and FEV1/FVC < 0.7, within 30 min after 4 puffs (4 x 100 µg) of salbutamol pMDI. If this criterion is not met at screening, the test can be repeated once before commencing of the run-in period.
6. Current or past smoker of at least 10 pack/years where one pack-year is equivalent to 20 cigarettes per day for 1 year. (If the subjects underwent smoking cessation therapy, it must be completed 3 months prior to the screening visit and smoking status should not change between the subjects screening visit and subjects last study visit).

E.4

Principal exclusion criteria

1. Pregnant or lactating female subjects.
2. Current diagnosis of Asthma.
3. Hospitalization for COPD or pneumonia within 3 months prior to screening and until randomization.
4. COPD exacerbations requiring systemic steroids and /or antibiotics and/or oral or nebulized β2-agonists in the 4 weeks prior to screening and until randomization.
5. LRTI in the 4 weeks prior to screening and until randomization.
6. Patients with serum potassium levels < 3.5 mEq/L.
7. Known respiratory disorders other than COPD including but not limited to α1 antitrypsine deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, restrictive lung disease and interstitial lung disease.
8. Intolerance or contra-indication to treatment with β2-agonists and/or inhaled corticosteroids or allergy to any component of the study treatments.
9. Having received an investigational drug within 2 months before the screening visit.
10. Patients treated with non-cardioselective β-blockers in the month preceding the screening visit or during the study period.
11. Patients who have clinically significant cardiovascular disease according to investigator’s judgement. Thus includes but is not limited to congestive heart failure (NYHA class > 3); acute ischemic heart disease within the past 12 months of screening; Sustained cardiac arrhythmias (supraventricular or ventricular, >30 seconds duration) at or within 6 months of screening; Non sustained cardiac arrhythmias (supraventricular or ventricular, > 3 beats < 30 seconds and or ending spontaneously and or asymptomatic); History of sustained and non-sustained cardiac arrhythmias (supraventricular or ventricular); 2nd or 3rd degree AV conduction block; Left Bundle Branch Block.
12. Known respiratory disorders other than COPD
13. Patients whose DBP/SBP is higher than: DBP 90 mmHg or SBP 160 mmHg at screening or at randomization.
14. Patients taking Cardiac Anti-Arrythmics drugs, chronically or in the 4 weeks preceding the Screening Visit, patients taking oral/IV/IM corticosteroids, oral or nebulized β2-agonists and/or antibiotics for LRTI and xanthine derivative (e.g. theophylline) formulations in the 4 weeks preceding the screening visit.
15. Unstable concurrent disease
16. Any patient with active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized basal cell carcinoma
(without metastases) of the skin is acceptable

E.5 End points

E.5.1

Primary end point(s)

Average 4-hour Heart Rate

E.5.1.1

Timepoint(s) of evaluation of this end point

4-hour rate

E.5.2

Secondary end point(s)

Cardiovascular:
• Average Hourly HR 0-1hr, 1-2hr, 2-3hr, 3-4hr
• Maximum 4-hour Heart Rate
• Average 0-12 hour Heart Rate
• Heart Rate at 5 minutes post-dose (expected time of Formoterol Cmax)
• QTcF, PR, QRS
• PAC burden
• PVC burden
• Blood Pressure: SBP AUC0-12h/12h, DBP AUC0-12h/12h

Metabolic response:
• Serum Potassium (AUC0-4h, Cmin, tmin)
• Serum Glucose (AUC0-4h, Cmax, tmax)

E.5.2.1

Timepoint(s) of evaluation of this end point

See section E.5.2

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

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

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, pharmacology

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

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

partial blind

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.8.2.4

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will receive appropriate medical care after termination of the study.

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

2013-10-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-04-11

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