Bronchodilator Properties and Safety in Asthma

Bronchodilator Properties and Safety of a Repeated Dose of V0162 in Asthma.

Recent large clinical studies have demonstrated the interest of LAMA therapy in the management of asthma, when compared to LABA.

V0162 is a compound with a very long lasting bronchodilator effect when compared to reference treatment in non-clinical models and in COPD patients. Secondary properties of V0162 (i.e.H1/H4 and PDE IV-inhibition) could enhance the efficacy of this antimuscarinic compound and could bring option in the treatment obstructive lung disease. The objective of the study is to assess the bronchodilator properties of V0162 during 8 days in adult patients with asthma usually treated with ICS and LABA. The study is a randomised, double-blind, placebo-controlled, 3-period crossover, preceded by an open-label active-control period before randomisation.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Other: Placebo; Drug: V0162

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Gauting, Germany
    • CRO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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:
• 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.

Exclusion Criteria:

• 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
• Severe hepatic impairment, moderate to severe renal impairment, epilepsy, narrow angle glaucoma, gastrointestinal obstruction, 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; Placebo	Other: Placebo
Experimental: V0162 dose1	Drug: V0162
Experimental: V0162 dose2	Drug: V0162

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalised AUC 0-24h of FEV1 at day 8 of treatment period	FEV1 assessed by spirometry	At the 8th day of treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parameters of the pulmonary function	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 periodadjusted for placebo effect: the normalised AUC0-9h of FEV1 (L),; the normalised AUC0-12h 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 AUC0-9h,AUC0-12h, AUC0-24h, peak and trough of FVC, MEF25, MEF50, MEF75, and MEF25-75.	Day 1 and Day 8 of treatment period
PEF	PEF measured using a peak-flow meter	Morning and evening from Day 1 to day 8 of treatment period
Dyspnoea	The criteria will be the normalised AUC0-9h,AUC0-12h, and AUC0-24h 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.	Day 1 to Day 8 of treatment period
Vital signs		Visit 2, and at Visit 3 to Visit 10 (within 30 min pre-dose and 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 24 h post-dose during the in-clinic visits) and at Visit 11
12-lead standard ECG		at Visit 1, at Visit 3 to Visit 10 (within 30 min pre-dose and 15 min, 1 h, 6 h, 24 h post-dose) and at Visit 11
Holter-ECG		At Visit 3 to Visit 10 : from 30 min pre-dose to 12 hours post-dose
Clinical laboratory tests (haematology, biochemistry, urinalysis)		Visit 1 and Visit 11
AEs		From Visit 1 to Visit 11
Normalised AUC 0-24h of FEV1 at Day 1 of treatment period	FEV1 assessed by spirometry	The first day of treatment period
Difference between day 8 and first day of treatment period in normalised AUC 0-24h of FEV1	FEV1 assessed by spirometry	Difference between day 8 and first day of treatement period

Collaborators and Investigators

• Sponsor: Pierre Fabre Medicament

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: September 5, 2013
• First Submitted That Met QC Criteria: September 23, 2013
• First Posted (Estimate): September 26, 2013

Study Record Updates

• Last Update Posted (Estimate): September 17, 2014
• Last Update Submitted That Met QC Criteria: September 16, 2014
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Asthma, COPD, broncodilator, airway, lung, inhalation, antimuscarinic
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 2013-002517-35