Phase II Open-Label Pilot Study of V3381 in Chronic Cough

Phase II Open-label Pilot Study of V3381, a Novel N-Methyl-D-Aspartate Receptor Antagonist, in Chronic Cough Patients Attending a Specialist Clinic

The investigators hypothesise that cough reflex hypersensitivity, demonstrated in chronic cough patients, is due to a phenomenon known as central sensitisation. Central sensitisation is a hyper-excitability of the sensory nerves as they join the central nervous system, and is believed to be mediated by the N-Methyl-D-Aspartate (NMDA) receptor[1-3].

Study Overview

• Status: Terminated
• Conditions: Cough
• Intervention / Treatment: Drug: Indantadol

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M23 9LT
    • South Manchester University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female 18-75 years of age
• Females must be of non child-bearing potential
• Chronic Cough ( > 8 weeks)
• Normal Chest X-ray
• Normal Lung Function
• Idiopathic or treatment resistant cough-

Exclusion Criteria:

• Recent upper respiratory tract infection (<4 weeks)
• Pregnancy/breast-feeding
• Current smokers or ex-smokers with <6 months abstinence or cumulative history of >10 pack years
• Current treatment with ACE inhibitors.
• Drug or alcohol abuse
• Uncontrolled hypertension (i.e., >140/90 mmHg despite adequate medical therapy).
• Any cardiovascular condition that would be a contra-indication to the use of sympathomimetic amines (e.g. active angina).
• Any clinically significant neurological disorder
• Prior renal transplant, current renal dialysis.
• Any clinically significant or unstable medical or psychiatric condition that would interfere with the patient's ability to participate in the study.
• Increased risk of seizures.
• Any malignancy in the past 2 years (with the exception of basal cell carcinoma).
• Use of opioids, anticonvulsants, antidepressants (particularly MAO inhibitors).
• Any clinically significant abnormal laboratory test result(s).
• Serum creatinine laboratory value greater than 1.5 x upper limit of normal (ULN) reference range (after adjustment for age) or estimated creatinine clearance <60 mL/min.
• Total bilirubin greater than upper limit of normal reference range (with the exception of Gilbert's Syndrome) and/or alanine transaminase (ALT) >1.5 times upper limit of normal reference ranges (after adjustment for age).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective cough frequency at 8 weeks compared to baseline.	8 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in objective cough frequency at 4 weeks.	4 Weeks
Change in Cough-Specific Quality-of-Life Questionnaire (CQLQ) at 4 and 8 weeks.	4 and 8 Weeks
Change in Global Rating of Change Scale at 1 week, 2 weeks, 4 weeks and 8 weeks	1 Week, 2 Weeks, 4 Weeks and 8 Weeks

Collaborators and Investigators

• Sponsor: Vernalis (R&D) Ltd
• Collaborators: Manchester University NHS Foundation Trust
• Investigators: Principal Investigator: Ashley Woodcock, Prof., South Manchester University Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: July 21, 2011
• First Submitted That Met QC Criteria: July 22, 2011
• First Posted (Estimate): July 25, 2011

Study Record Updates

• Last Update Posted (Estimate): July 25, 2011
• Last Update Submitted That Met QC Criteria: July 22, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Chronic Cough; Indantadol
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough
• Other Study ID Numbers: V001