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

• Conditions: Asthma; MedDRA version: 16.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2013-002517-35-DE
• Lead Sponsor: Pierre Fabre Médicament/Institut de Recherche Pierre Fabre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07-02
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Objective: To assess the effect on rescue medication use and the general and local safety of V0162 inhalation powder.;Primary end point(s): The main criterion will be the normalised AUC0-24h of FEV1 (L) assessed the last day of each treatment period. ;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