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

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2013-002517-35-DE
• Date of registration: 02/07/2013
• Prospective Registration: Yes
• Primary sponsor: Pierre Fabre Médicament/Institut de Recherche Pierre Fabre
• Public title: Bronchodilator properties and safety of a repeated dose of V0162 inhalation powder in asthma
• Scientific title: Bronchodilator properties and safety of a repeated dose of V0162 inhalation powder in asthma
• Date of first enrolment: 05/09/2013
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002517-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: Preceded by an open-label active-control period before randomisation If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Germany

Contacts

• Name: Dr Lucilla MANSUY
• Affiliation: Institut de Recherche Pierre Fabre-Pierre Fabre Innovation

• Name: Dr Lucilla MANSUY
• Affiliation: Institut de Recherche Pierre Fabre-Pierre Fabre Innovation

Key inclusion & exclusion criteria

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

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)



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Asthma
MedDRA version: 16.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Code: V0162
Pharmaceutical Form: Capsule, hard
Current Sponsor code: V0162
Other descriptive name: D-MEQUITAZINE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 800-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Inhalation use

Trade Name: SPIRIVA 18 microgrammes
Pharmaceutical Form: Capsule, hard
CAS Number: 411207-31-3
Other descriptive name: TIOTROPIUM BROMIDE MONOHYDRATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

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

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

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

Main Objective: 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.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: for more details, please refer to the protocol

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.

Secondary ID(s)

V00162PI2024A

Source(s) of Monetary Support

Institut de Recherche Pierre Fabre