Clinical Trials Register

Summary
EudraCT Number:	2013-002517-35
Sponsor's Protocol Code Number:	V00162PI2024A
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-07-02
Trial results	Removed from public view

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

Germany - BfArM

A.2

EudraCT number

2013-002517-35

A.3

Full title of the trial

Bronchodilator properties and safety of a repeated dose of V0162 inhalation powder in asthma

A.3.1

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

Bronchodilator properties and safety of a repeated dose of V0162 inhalation powder in asthma

A.4.1

Sponsor's protocol code number

V00162PI2024A

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	Pierre Fabre Médicament/Institut de Recherche Pierre Fabre
B.1.3.4	Country	France
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	Institut de Recherche Pierre Fabre
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Institut de Recherche Pierre Fabre-Pierre Fabre Innovation
B.5.2	Functional name of contact point	Dr Lucilla MANSUY
B.5.3	Address:
B.5.3.1	Street Address	Centre de R&D Pierre Fabre-3 avenue Hubert Curien-BP 13562
B.5.3.2	Town/ city	Toulouse Cédex 1
B.5.3.3	Post code	31035
B.5.3.4	Country	France
B.5.4	Telephone number	33 (0)534 506339
B.5.5	Fax number	33(0)534 506220
B.5.6	E-mail	lucilla.mansuy@pierre-fabre.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.3.2	Product code	V0162
D.3.4	Pharmaceutical form	Capsule, hard
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.3.9.2	Current sponsor code	V0162
D.3.9.3	Other descriptive name	D-MEQUITAZINE
D.3.9.4	EV Substance Code	SUB29977
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	800
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	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 18 microgrammes
D.2.1.1.2	Name of the Marketing Authorisation holder	BOEHRINGER INGELHEIM INTERNATIONAL GmbH
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Capsule, hard
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	411207-31-3
D.3.9.3	Other descriptive name	TIOTROPIUM BROMIDE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB21897
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)	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	Capsule, hard
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

Asthma

E.1.1.1

Medical condition in easily understood language

Asthma

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	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
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 assess the bronchodilator properties of V0162 inhalation powder delivered once daily during 8 days in adult patients with asthma usually treated with ICS and LABA.

E.2.2

Secondary objectives of the trial

To assess the effect on rescue medication use and the general and local safety of V0162 inhalation powder.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria (checked on Visit 1):
-Male or female gender.
-Aged 18 to 65 years-old.
-18 ≤ BMI <30 kg/m².
-Clinical history consistent asthma, in the judgement of the investigator.
-Asthma controlled or partly controlled according to GINA 2012 criteria:
Less than three of the following items present over the last week:
1)daytime symptoms more than twice a week,
2)any limitation of activities,
3)any nocturnal symptoms/awakening,
4)need of reliever/rescue treatment more than twice a week
-Asthma treated by ICS and LABA (fixed-dose combination or free combination) at stable dose for at least 3 months.
-Able to replace the usual ICS and LABA therapy by ICS at the usual dose regimen and salbutamol as needed.
-Able to stop salbutamol at least 6 hours before a study visit.
-Able to perform at least 3 acceptable and reproducible FEV1 and FVC measurements according to ERS/ATS 2005 recommendations.
-For woman of child bearing potential: negative urine or serum pregnancy test at inclusion and using an efficient contraceptive (surgical or hormonal birth control or intra-uterine device) for at least 2 months before the study and one month after the end of the study, in order to avoid pregnancy while being exposed to the study treatment.
-Having signed the Informed Consent Form.
-Likely to be compliant during the study, in the judgement of the investigator.
-Affiliated to the social security system or being a beneficiary.

Inclusion criteria (checked on Visit2):
-No use of salbutamol within the last 6 hours.
-No use of ultra long-acting Beta2-agonist (indacaterol) and/or long-acting muscarinic-antagonists within the last 48 hours.
-No use of xanthines or antileukotrienes within the last week.
-No use of oral and/or intravenous corticosteroids within the last 4 weeks.
-No use of depot and/or intramuscular corticosteroids within the last 6 months.
-No use of antihistamines within the last week.
-Pre-bronchodilation FEV1≥ 60% of the predicted normal value.
-Reversibility demonstrated by a FEV1 increase ≥12% ((FEV1 post-bronchodilation – FEV1 pre-bronchodilation) / FEV1 pre-bronchodilation) and ≥ 0.200 L (FEV1 post-bronchodilation – FEV1 pre-bronchodilation), 10-20 minutes after acute administration of 4x100 µg salbutamol.

Inclusion criteria (checked on Visits 3 and 5):
-Asthma controlled or partly controlled according to GINA 2012 criteria:
Less than three of the following items present over the last week:
1)daytime symptoms more than twice a week,
2)any limitation of activities,
3)any nocturnal symptoms/awakening,
4)need of reliever/rescue treatment more than twice a week, considering salbutamol use as reliever if intake exceeds 4 times 2 inhalations per day (taking into account LABA being replaced by salbutamol)

Stability criterion (checked on Visits 5, 7 and 9):
-Difference of the measured FEV1 (L) value compared to the previous measurement ≤ 30% (Visit 5 vs Visit 3, Visit 7 vs Visit 5, Visit 9 vs Visit 7)
If a patient fails to meet that stability criterion, the respective visit may be rescheduled twice.

E.4

Principal exclusion criteria

Non-inclusion criteria (checked on Visit 1)
Criteria related to pathologies
-History of aspirin intolerance or aspirin-induced asthma.
-History of life-threatening asthma within 5 years (i.e., brittle asthma or requiring hospitalisation in ICU).
-Clinically significant respiratory conditions other than asthma (e.g. pneumonia, pneumothorax, atelectasis, bronchiectasis, chronic bronchitis, COPD, emphysema, pulmonary arterial hypertension, pulmonary fibrosis,etc.).
-Upper or lower respiratory tract infection within 4 weeks.
-Exacerbation (requiring oral corticosteroids or hospitalization) within 3 months.
-Current smoker or former smoker less than 6 months or total lifetime smoking history greater than 10 pack-years.
-Intolerance to salbutamol.
-Intolerance to tiotropium (or any other atropine-derived compound).
-Intolerance to one of the ingredients of the study product: mequitazine (and more generally all phenothiazine-derived compounds) and lactose.
-Severe hepatic impairment, moderate to severe renal impairment, epilepsy, narrow angle glaucoma, moderate to severe prostatic hypertrophy, bladder neck obstruction.
-Any acute or chronic disease that will not allow the participation in the study, in the judgement of the investigator.
-Clinically relevant physical examination abnormality.
-Abnormal vital signs (SBP > 140 or < 90 mmHg; DBP > 90 or < 60 mmHg; HR > 100 or < 40 bpm in supine position, unless decision of the Investigator).
-Abnormal and clinically significant 12-lead ECG (HR > 100 or < 40 bpm, PR > 220 or < 100 ms, QRS > 120 ms, QTcF > 450 ms).
-Congenital long QT syndrome, known or suspected prolongation of QT interval (QTcF > 450 ms), heart failure, hypokalemia, family history of Long QT syndrome, use of concomitant medications that prolong the QT/QTc interval.
-Clinically relevant biological (haematology, biochemistry and urinary) exam abnormality, in particular hypokalemia.

Criteria related to the population
-Pregnancy or in post-partum period or nursing mother.
-Alcohol abuse (more than 28 units (male) or 21 units (female) of alcohol a week (unit = 1 glass of wine = 1 glass of spirits = ½ pint of beer)).
-Drug abuse.
-Positive serology to HIV antibodies, HCV antibodies and/or HBs antigen.
-Patients who cannot maintain regular day/night, waking/sleeping cycles (e.g. night shift workers).
-Patients who are not able to understand the information (for linguistic or psychiatric reasons), in the judgement of the investigator.
-Patients who had forfeited their freedom by administrative or legal decision, or who are under guardianship or wardship.
-Patients who cannot be contacted by phone in an emergency.
-Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Selection Visit (Visit 1)

E.5 End points

E.5.1

Primary end point(s)

The main criterion will be the normalised AUC0-24h of FEV1 (L) assessed the last day of each treatment period.

E.5.1.1

Timepoint(s) of evaluation of this end point

30 min pre-dose and 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 22 h, 23 h, 24 h post-dose

E.5.2

Secondary end point(s)

The secondary criteria, for spirometry, will be
•the normalised AUC 0-24h of FEV1 (L) assessed the first day of each treatment period,
•the difference between the last and the first day of each treatment period in normalised AUC 0-24h of FEV1 (L) adjusted for placebo effect,
as well as the following criteria assessed the first day and the last day of each treatment period and the difference between the last day and the first day within each treatment period adjusted for placebo effect:
•the normalised AUC 0-9h of FEV1 (L),
•the normalised AUC 0-12h of FEV1 (L),
•the peak of FEV1 (L) which is the higher observed post-dosing value,
•the trough of FEV1 (L) which is the last measurement before the next dosing (i.e. t24h),
•the normalised AUC 0-9h, AUC 0-12h, AUC 0-24h, peak and trough of FVC, MEF25, MEF50, MEF75, and MEF25-75.
All the above spirometry criteria made of normalized AUCs will also be derived as baseline-adjusted normalised AUCs, baseline being defined as the predose measurement at the first day of each treatment period.
The secondary criteria for PEF will be the mean of the daily morning measurements and the daily evening measurements from the first to the last day within each treatment period.
The secondary criteria for dyspnoea measurements will be the normalised AUC 0-9h, AUC 0-12h, and AUC 0-24h of the dyspnoea measurements (mm) assessed the first and the last day of each treatment period, and the difference between the last and the first day within each treatment period.
The secondary criteria for rescue medication use will be the number of puffs of rescue medication and the number of days without use during each treatment period.

E.5.2.1

Timepoint(s) of evaluation of this end point

for more details, please refer to the protocol

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

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

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

Preceded by an open-label active-control period before randomisation

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.8.4.1

Number of sites anticipated in 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 months

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)

None

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

2013-09-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-04-22

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