Clinical Trials Register

Summary
EudraCT Number:	2015-005550-35
Sponsor's Protocol Code Number:	CCD-06001AA1-10
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:	2016-07-15
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

2015-005550-35

A.3

Full title of the trial

A RANDOMISED, DOUBLE-BLIND, PLACEBO CONTROLLED, REPEATED DOSE, THREE-WAY CROSSOVER STUDY TO EVALUATE THE PHARMACODYNAMICS, PHARMACOKINETICS AND SAFETY OF TWO DOSES OF CHF 6001 DPI IN SUBJECTS WITH MODERATE, SEVERE COPD.

A.3.1

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

A clinical trial to evaluate the evolution of a new medicine, CHF 6001 DPI in patients with chronic lung obstruction

A.4.1

Sponsor's protocol code number

CCD-06001AA1-10

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	Clinical Project Manager
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	+39 0521 1689215
B.5.6	E-mail	clinicaltrials_info@chiesi.com

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	CHF 6001 400µg/10 mg NEXThaler® DPI
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.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	CHF 6001
D.3.9.3	Other descriptive name	CHF 6001
D.3.9.4	EV Substance Code	SUB180242
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	400
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	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

E.1.1.1

Medical condition in easily understood language

difficulty in 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	19.0
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 evaluate the effect of CHF 6001 on biomarkers of inflammation in induced sputum and in blood

E.2.2

Secondary objectives of the trial

To evaluate the effect of CHF 6001 on biomarkers of inflammation on pulmonary function and on symptoms benefits in comparison with placebo
To evaluate the safety and tolerability of CHF 6001
To assess the pharmacokinetics profile of CHF 6001 and its metabolites at steady state in subjects with moderate, severe COPD.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female aged ≥ 40 years
2. A female is eligible to enter the study if she is of non-childbearing potential i.e. physiologically incapable of becoming pregnant
3. Subjects with an established diagnosis of COPD (according to GOLD guidelines, update 2015) at least 12 months prior to the screening visit
4. With a smoking history of at least 10 pack-years [pack-years=number of cigarettes per day x number of years/20]. Current and ex- smokers are eligible. (Smoking cessation must be at least 3 months prior to the screening.
5. With a BMI in the range of 18-35 Kg/m2
6. With a post- bronchodilator FEV1 ≥ 30% and ≤ 70% of the subject normal predicted value and a post-bronchodilator FEV1/FVC ratio <0.70 measured 10-15 minutes after 400µg (4 puffs x 100µg) of salbutamol pMDI. If this criterion is not met at screening, the test can be repeated once before randomisation visit.
7. Subjects must be receiving daily maintenance with triple therapy (ICS plus LABA plus LAMA) at stable dose and dosing regimen, for at least 2 months prior to screening
8. With a history of chronic bronchitis defined as chronic cough and sputum production for more than three months per year for two or more years and known as ‘spontaneous sputum producer’ subject
9. At screening, subjects must be able to produce an adequate induced sputum sample defined as a load of at least 300 mg with a viability factor of not less than 70% (with less than 30% epithelial cells) and a neutrophil % differential count of at least 60%.
10. Subjects must be symptomatic at screening defined as having a CAT score ≥10

E.4

Principal exclusion criteria

1. Pregnant or lactating female subject
2. Subjects with a current diagnosis of asthma
3. Subjects with a moderate or severe COPD exacerbation [i.e. resulting in the use of systemic (oral/IV/IM corticosteroids) and/or antibiotics or in hospitalisation] or a lower respiratory tract infection within 6 weeks prior to study entry or during the screening period
4. Subjects on maintenance bronchodilators therapy only (LABA alone, LAMA alone, dual LABA/LAMA alone) or maintenance dual therapy only (ICS/LABA or ICS plus LAMA) within 2 months prior to study entry
5. Subjects on PDE4 inhibitors (e.g. roflumilast) within 2 months prior to study entry
6. Subjects requiring long-term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
7. Subjects participating to a pulmonary rehabilitation programme or completing such a programme within the last 6 weeks prior to study entry
8. Subjects with known respiratory disorders other than COPD that in investigator’s opinion would affect efficacy and safety evaluation or place the subject at risk. This can include but is not limited to known alpha-1 antitrypsin deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease
9. Subjects with active (lung) cancer or a history of lung cancer ;or a history of cancer other than lung cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized carcinoma (e.g. basal cell carcinoma (without metastases), in situ carcinoma of the cervix adequately treated,) is acceptable
10. Subjects with a known history of hypersensitivity to β2-agonist, PDE4 inhibitors or any of the excipients contained in any of the formulations used in the trial
11. Subjects who have known history of clinically significant cardiovascular conditions such as, but not limited to, unstable or acute ischemic heart disease within one year prior to study entry, NYHA Class III/IV heart failure, known history of sustained and non-sustained cardiac arrhythmias or history of atrial fibrillation diagnosed in the last 6 months prior to study entry and not controlled with therapy rate control strategy as well as subjects with a history or symptoms of significant neurological disease including transient ischemic attack (TIA), stroke, seizure disorder or behavioural disturbances
12. Male subjects with a QTcF >450 ms and female subjects with a QTcF >470 ms at screening and/or at randomisation visits
13. Subjects who have unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment, significant renal impairment; history of cerebrovascular disease; uncontrolled gastrointestinal disease (e.g. active peptic ulcer, Crohn’s disease, ulcerative colitis, enteritis, unexplained diarrhea, bloody or loose stools); uncontrolled haematological disease; uncontrolled autoimmune disorders (e.g. rheumatoid arthritis, inflammatory bowel disease) or other disease or condition that might, in the judgement of the investigator , place the subject at undue risk or potentially compromise the results or interpretation of the study
14. Subjects with abnormal alanine aminotransferase (ALT) ≥2x upper limit of normal (ULN) and/ or aspartate aminotransferase (AST) ≥2x ULN and/or bilirubin ≥1.5x ULN. Isolated bilirubin ≥1.5x ULN is acceptable if fractionated and direct bilirubin is <35%
15. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)
16. Subjects receiving treatment with any drug known to have a well-defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole) within the previous 3 months prior to the study entry
17. Subjects have experienced excessive weight loss recently (which cannot be explained by the natural course of COPD or known background conditions).
18. Subjects with a history of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit
19. Subjects having received any other investigational drug within the preceding 30 days (60 days for biologics), or a longer and more appropriate time as determined by the Investigator (e.g., approximately five half-lives of the previous investigational drug).

E.5 End points

E.5.1

Primary end point(s)

Pharmacokinetic: Plasma: AUC0-12h,ss, Cmin,ss, Cmax,ss, Cav,ss, tmax,ss, tmin,ss,CL/Fss (for CHF 6001 only), calculated from the individual 0-12h plasma concentration time
profiles of CHF 6001 and its main metabolites CHF 5956 and CHF 6095 on
Day 32 at steady state.
sputum cell count and biomarkers

E.5.1.1

Timepoint(s) of evaluation of this end point

on Day 32 at steady state

E.5.2

Secondary end point(s)

1/ blood biomarkers
2/ lung function
3/ TDI, CAT scores
4/ PK parameters
5/ Safety (AEs, ADRs, vital signs)

E.5.2.1

Timepoint(s) of evaluation of this end point

on day 32, except for AE ADR

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

Yes

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

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

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

see protocol

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

2016-09-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-09-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-12-28

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