Safety, Preliminary Pharmacokinetics and Bronchodilator Properties of V0162

Pulmonary administered anticholinergic agents have shown their importance in the chronic obstructive pulmonary disease (COPD) management to reduce morbidity, disability and mortality. To date, the recommended treatment of moderate to severe COPD patients consist in the combination of ß2 agonist and long acting antimuscarinic compounds. There is still a medical need in new product that could exhibit both anti-inflammatory and strong bronchodilation potency. V0162 is a compound with a potent anticholinergic activity.

Secondary PD properties of V0162 could enhance the efficacy of this antimuscarinic compound and could bring new option in the treatment of this life-threatening disease.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Bronchodilatator

Detailed Description

This study has two parts. Part A will be conducted in 72 healthy volunteers. Part B will be conducted in 20 patients diagnosed with COPD.

Part A The primary objective of this part of the study is to assess the local tolerability of escalating doses of V0162 in male healthy volunteers.

Part B The primary objective of this part of the study is to assess the bronchodilator properties of V0162 at the maximal tolerated dose (determined in Part A) in COPD patients.

In addition, pharmacokinetics and vital sign including ECG will be determined.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Anvers, Belgium
    • SGS
• France
  • Paris, France
    • SGS Aster SAS

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria Part A:

• Male gender
• Age between 18 to 50 years included,
• 18 ≤ Body Mass Index (BMI) < 30 kg/m²,
• Who had given their written consent for their participation in the study,
• Who, in the judgement of the Investigator, are likely to be compliant during the study,
• Registered with a social security insurance system.

Inclusion Criteria Part B:

• Aged 40 to 65 years-old,
• 18 ≤ BMI < 35 kg/m2,
• Smokers ≥ 10 packs / year,
• Moderate to severe COPD
• Registered with a social security insurance system.

Exclusion Criteria Part A:

• History of asthma or significant respiratory disorder,
• History of allergic rhinitis,
• Upper respiratory tract infection in the last month,
• Blood eosinophil count ≥ 600/μL,
• Epilepsy, narrow angle glaucoma, prostatic hypertrophy or bladder neck obstruction,
• Abnormal spirography,

Exclusion Criteria Part B:

• Respiratory tract infection in the last 6 weeks,
• Asthma or significant respiratory disorder other than COPD,
• Allergic rhinitis,
• Blood eosinophil count ≥ 600/μL,
• Epilepsy, narrow angle glaucoma, moderate to severe prostatic hypertrophy or bladder neckobstruction,
• Myocardial infarction within the previous 6 months, heart failure or serious cardiac arrhythmia,
• Moderate to severe renal impairment,
• Moderate to severe hepatic impairment
• Use of short-acting b-agonist,
• Use of anticholinergics

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Bronchodilatator
Experimental: V0162	Drug: Bronchodilatator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the local tolerability of V0162 in healthy male volunteers	Monitoring of parameters of the pulmonary function: spirometry measurements. Assessment of respiratory system symptoms: using a 4-point scale and assessment of dyspnoea by VAS. Monitoring for the occurrence of AEs. Changes in physical examination: vital signs (blood pressure and pulse rate), holter-ECG and clinical laboratory tests (biochemistry, haematology, urinalysis).	change from baseline in the local tolerability over 72 h after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the PK parameters of V0162 in healthy male volunteers	Pharmacokinetics: evaluation of the PK parameter of V0162 (measured by area under the plasma concentration-time curve (AUC)) after oral administration and of the dose proportionality.	0, 5, 15, 30, 45 min, 1, 2, 4, 8, 12, 24, 48 and 72 h after dosing
To assess the bronchodilator properties of V0162 in COPD	Monitoring of parameters of the pulmonary function through plethysmography measurements.	0, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 14, 20, 24, 28 and 32 h after dosing

Collaborators and Investigators

• Sponsor: Pierre Fabre Medicament
• Collaborators: SGS Life Sciences, a division of SGS Belgium NV

Publications and helpful links

General Publications

• Devillier P, Garrigue E, D'Auzers G, Monjotin N, Similowski T, Clerc T. V0162 a new long-acting bronchodilator for treatment of chronic obstructive lung diseases: preclinical and clinical results. Respir Res. 2015 Jun 8;16(1):68. doi: 10.1186/s12931-015-0227-1.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: April 13, 2011
• First Submitted That Met QC Criteria: May 4, 2011
• First Posted (Estimate): May 5, 2011

Study Record Updates

• Last Update Posted (Estimate): June 4, 2013
• Last Update Submitted That Met QC Criteria: June 3, 2013
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: V00162 PI 101 1A