Clinical trial NCT03979638: A Dose Escalation Study of BLU-5937 in Unexplained or Refractory Chronic Cough
Official title: A Randomized, Double-Blind, Placebo-Controlled, Crossover, Dose Escalation Study of BLU-5937 in Subjects With Unexplained or Refractory Chronic Cough (RELIEF)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Refractory Cough
Keywords: Unexplained or refractory chronic cough, P2X3 antagonists
Lead sponsor: Bellus Health Inc. - a GSK company
Sponsor class: INDUSTRY
First posted: 2019-06-07
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Two-arm, Two-Period, crossover assignment
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized, double-blind, placebo-controlled, crossover, dose escalation study of BLU-5937 in subjects with unexplained or refractory chronic cough

Detailed description: This study will have two 16-day treatment periods (four escalating doses or matching placebo at four days interval) separated by a 10 to 14-day washout period. There will be a 14-day follow-up period.

Eligibility criteria: Inclusion Criteria:

* Unexplained or refractory chronic cough for at least one year
* Chest radiograph or CT thorax within the last 60 months not demonstrating any abnormality considered to be significantly contributing to the chronic cough
* Cough count of ≥ 10 per hour (Awake Cough Count) at Screening
* Score of ≥ 40mm on the Cough Severity VAS at Screening
* Women of child-bearing potential must have a negative serum pregnancy test at Screening
* Women of child-bearing potential must use a highly effective contraception method from Screening through the Follow-Up Visit
* Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control

Exclusion Criteria:

* Current smoker or individuals who have given up smoking within the past 6 months, or those with \>20 pack-year smoking history
* Diagnosis of COPD, bronchiectasis, idiopathic pulmonary fibrosis
* Treatment with an ACE-inhibitor as the potential cause of a subject's cough, or requiring treatment with an ACE-inhibitor during the study, or within 12 weeks prior to the Screening Visit
* FEV1/FVC \< 60%
* History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit
* History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening
* History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years
* Clinically significant abnormal electrocardiogram (ECG) or laboratory tests at Screening
* Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results

Primary outcomes:
measure: Change in Awake Objective Cough Frequency on Log-transformed Scale
timeFrame: Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses
Secondary outcomes:
Other outcomes:
measure: Change in Awake Cough Frequency on Log-transformed Scale in the Subgroup of Participants With Awake Cough Frequency > or = 20 Coughs/Hour at Baseline
timeFrame: Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses
measure: Change in Awake Cough Frequency on Log-transformed Scale in the Subgroup of Participants With Awake Cough Frequency > or = Median (32.4 Coughs/Hour) at Baseline
timeFrame: Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12,16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses
Locations:
city: San Diego
country: United States
facility: Allergy Associates Medical Group Inc.
state: California
city: San Jose
country: United States
facility: Allergy & Asthma Associates of Santa Clara Valley
state: California
city: Largo
country: United States
facility: Centre for Cough
state: Florida
city: Minneapolis
country: United States
facility: Clinical Research Institute
state: Minnesota
city: Gastonia
country: United States
facility: Clinical Research of Gastonia
state: North Carolina
city: Charleston
country: United States
facility: National Allergy & Asthma Research
state: South Carolina
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: Greenfield
country: United States
facility: Allergy Asthma & Sinus Center
state: Wisconsin
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester
city: Llanelli
country: United Kingdom
facility: Prince Phillip Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: Manchester Clinical Research Facility
city: North Shields
country: United Kingdom
facility: North Tyneside General Hospital
Study officials:
affiliation: University of Manchester
name: Jacky Smith, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: