Clinical trial NCT02993822: A Dose-ranging Study of Orvepitant in Patients With Chronic Refractory Cough
Official title: A Double-Blind, Randomized, Placebo Controlled Study of the Efficacy and Safety of Three Doses of Orvepitant in Subjects With Chronic Refractory Cough
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Refractory Cough
Lead sponsor: Nerre Therapeutics Ltd.
Sponsor class: INDUSTRY
First posted: 2016-12-15
Enrollment: 315
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effectiveness of three doses of orvepitant, taken once a day, in the treatment of chronic refractory cough.

Detailed description: A multi-center, double-blind, randomized, parallel group, placebo-controlled dose range study in subjects with chronic refractory cough (CRC).

Doses of orvepitant (10 mg/day, 20 mg/day and 30 mg/day) and placebo will be investigated in four parallel groups.

Each group will compromise of approximately 73 subjects, randomized 1:1:1:1 (approximately 292 subjects in total).

All subjects will enter a three-week screening period to determine eligibility. Eligible subjects will be randomized at the Baseline/Day 1 visit and enter a 12-week double-blind dosing period. During this period there will be four visits at Weeks 2, 4, 8 and 12. There will be a final safety follow-up visit at Week 14.

Eligibility criteria: Key Inclusion Criteria:

* Male and female subjects ≥18 years of age.
* Diagnosis of CRC or unexplained cough for at least 1 year (see ACCP/BTS guidelines attached).
* An awake average cough frequency of ≥10 coughs/ hour, as assessed using an ACM during the screening period.

Key Exclusion Criteria:

* Subjects with respiratory tract infection (\<4 weeks prior to study start)
* Current smokers or ex-smokers with \<6 months' abstinence or cumulative history of \>10 pack years
* Treatment with Angiotensin Converting Enzyme (ACE) inhibitors within 3 months of screening
* FEV1 \<80% predicted, measured at screening using spirometry
* History of cystic fibrosis, idiopathic pulmonary fibrosis, clinically significant bronchiectasis, moderate to severe asthma, chronic obstructive pulmonary disease (COPD)
* Any clinically significant abnormal laboratory test result(s)
* Inability to comply with the use of prohibited and allowed medications as described in the protocol.

Primary outcomes:
measure: Change From Baseline to Week 12 in Awake Objective Cough Frequency
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change in Awake Objective Cough Frequency at Week 2 Compared to Baseline
timeFrame: Baseline to Week 2
measure: Change in Awake Objective Cough Frequency at Week 4 Compared to Baseline
timeFrame: Week 4
measure: Change in the Leicester Cough Questionnaire (LCQ) at Week 2 Compared to Baseline
timeFrame: Baseline to Week 2
measure: Change in the Leicester Cough Questionnaire (LCQ) at Week 4 Compared to Baseline
timeFrame: Baseline to Week 4
measure: Change in the Leicester Cough Questionnaire (LCQ) at Week 8 Compared to Baseline
timeFrame: Baseline to Week 8
measure: Change in the Leicester Cough Questionnaire (LCQ) at Week 12 Compared to Baseline
timeFrame: Baseline to Week 12
measure: Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Day-time
timeFrame: Baseline to Week 2
measure: Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Day-time
timeFrame: Baseline to Week 4
measure: Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Day-time
timeFrame: Baseline to Week 8
measure: Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Day-time
timeFrame: Baseline to Week 12
measure: Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Night-time
timeFrame: Baseline to Week 2
measure: Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Night-time
timeFrame: Baseline to Week 4
measure: Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Night-time
timeFrame: Baseline to Week 8
measure: Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Night-time
timeFrame: Baseline to Week 12
measure: Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 2 Compared to Baseline
timeFrame: Baseline to Week 2
measure: Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 4 Compared to Baseline
timeFrame: Baseline to Week 4
measure: Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 8 Compared to Baseline
timeFrame: Baseline to Week 8
measure: Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 12 Compared to Baseline
timeFrame: Baseline to Week 12
measure: Global Rating of Change in Cough Frequency at Week 2
timeFrame: Baseline to Week 2
measure: Global Rating of Change in Cough Frequency at Week 4
timeFrame: Baseline to Week 4
measure: Global Rating of Change in Cough Frequency at Week 8
timeFrame: Baseline to Week 8
measure: Global Rating of Change in Cough Frequency at Week 12
timeFrame: Baseline to Week 12
measure: Global Rating of Change in Cough Severity at Week 2
timeFrame: Baseline to Week 2
measure: Global Rating of Change in Cough Severity at Week 4
timeFrame: Baseline to Week 4
measure: Global Rating of Change in Cough Severity at Week 8
timeFrame: Baseline to Week 8
measure: Global Rating of Change in Cough Severity at Week 12
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Study Site 15
state: Arizona
city: Los Angeles
country: United States
facility: Study Site 43
state: California
city: Mission Viejo
country: United States
facility: Study Site 52
state: California
city: San Diego
country: United States
facility: Study Site 20
state: California
city: San Jose
country: United States
facility: Study Site 28
state: California
city: Centennial
country: United States
facility: Study Site 25
state: Colorado
city: Colorado Springs
country: United States
facility: Study Site 36
state: Colorado
city: Waterbury
country: United States
facility: Study Site 48
state: Connecticut
city: Clearwater
country: United States
facility: Study Site 68
state: Florida
city: Jacksonville
country: United States
facility: Study Site 59
state: Florida
city: Largo
country: United States
facility: Study Site 12
state: Florida
city: Miami
country: United States
facility: Study Site 62
state: Florida
city: Miami
country: United States
facility: Study Site 57
state: Florida
city: Tampa
country: United States
facility: Study Site 33
state: Florida
city: Winter Park
country: United States
facility: Study Site 11
state: Florida
city: Meridian
country: United States
facility: Study Site 60
state: Idaho
city: Normal
country: United States
facility: Study Site 39
state: Illinois
city: Baltimore
country: United States
facility: Study Site 34
state: Maryland
city: Edina
country: United States
facility: Study Site 42
state: Minnesota
city: Minneapolis
country: United States
facility: Study Site 41
state: Minnesota
city: Rochester
country: United States
facility: Study Site 37
state: Minnesota
city: Missoula
country: United States
facility: Study Site 27
state: Montana
city: Las Vegas
country: United States
facility: Study Site 16
state: Nevada
city: Rochester
country: United States
facility: Study Site 32
state: New York
city: Charlotte
country: United States
facility: Study Site 55
state: North Carolina
city: Charlotte
country: United States
facility: Study Site 24
state: North Carolina
city: Charlotte
country: United States
facility: Study Site 53
state: North Carolina
city: Gastonia
country: United States
facility: Study Site 50
state: North Carolina
city: Greensboro
country: United States
facility: Study Site 54
state: North Carolina
city: Mooresville
country: United States
facility: Study Site 73
state: North Carolina
city: Raleigh
country: United States
facility: Study Site 71
state: North Carolina
city: Cincinnati
country: United States
facility: Study Site 56
state: Ohio
city: Oklahoma City
country: United States
facility: Study Site 74
state: Oklahoma
city: Tulsa
country: United States
facility: Study Site 26
state: Oklahoma
city: East Providence
country: United States
facility: Study Site 38
state: Rhode Island
city: Charleston
country: United States
facility: Study Site 21
state: South Carolina
city: Charleston
country: United States
facility: Study Site 72
state: South Carolina
city: Dallas
country: United States
facility: Study Site 22
state: Texas
city: Dallas
country: United States
facility: Study Site 35
state: Texas
city: Houston
country: United States
facility: Study Site 10
state: Texas
city: San Antonio
country: United States
facility: Study Site 49
state: Texas
city: Waco
country: United States
facility: Study Site 23
state: Texas
city: Salt Lake City
country: United States
facility: Study Site 58
state: Utah
city: Charlottesville
country: United States
facility: Study Site 19
state: Virginia
city: Bellingham
country: United States
facility: Study Site 14
state: Washington
city: Greenfield
country: United States
facility: Study Site 13
state: Wisconsin
city: Niagara Falls
country: Canada
facility: Study Site 66
state: Ontario
city: Québec
country: Canada
facility: Study Site 65
state: Quebec
city: Trois-Rivières
country: Canada
facility: Study Site 64
state: Quebec
city: Romford
country: United Kingdom
facility: Study Site 29
state: Essex
city: Blackpool
country: United Kingdom
facility: Study Site 94
state: Lancashire
city: Prescot
country: United Kingdom
facility: Study Site 93
state: Merseyside
city: Northwood
country: United Kingdom
facility: Study Site 17
state: Middlesex
city: Belfast
country: United Kingdom
facility: Study Site 40
state: Northern Ireland
city: Barnsley
country: United Kingdom
facility: Study Site 96
state: South Yorkshire
city: Cannock
country: United Kingdom
facility: Study Site 97
state: Staffordshire
city: Stockton-on-Tees
country: United Kingdom
facility: Study Site 95
state: Teesside
city: Hull
country: United Kingdom
facility: Study Site 45
city: Leeds
country: United Kingdom
facility: Study Site 92
city: Leicester
country: United Kingdom
facility: Study Site 30
city: London
country: United Kingdom
facility: Study Site 46
city: Manchester
country: United Kingdom
facility: Study Site 91
city: Manchester
country: United Kingdom
facility: Study Site 18
city: Newcastle Upon Tyne
country: United Kingdom
facility: Study Site 47
city: North Shields
country: United Kingdom
facility: Study Site 31
city: Oxford
country: United Kingdom
facility: Study Site44
Study officials:
References: