A Dose-ranging Study of Orvepitant in Patients With Chronic Refractory Cough
- Conditions
- Chronic Refractory Cough
- Interventions
- Drug: Placebo
- Registration Number
- NCT02993822
- Lead Sponsor
- Nerre Therapeutics Ltd.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 315
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Orvepitant 20mg Orvepitant Maleate Orvepitant 20mg tablet, once daily for 12 weeks Orvepitant 30mg Orvepitant Maleate Orvepitant 30mg tablet, once daily for 12 weeks Placebo Placebo Placebo to match tablet, once daily for 12 weeks Orvepitant 10mg Orvepitant Maleate Orvepitant 10mg tablet, once daily for 12 weeks
- Primary Outcome Measures
Name Time Method Change From Baseline to Week 12 in Awake Objective Cough Frequency Baseline to Week 12 Objective cough frequency measured by ambulatory cough monitoring device
- Secondary Outcome Measures
Name Time Method Change in Awake Objective Cough Frequency at Week 2 Compared to Baseline Baseline to Week 2 Objective cough frequency measured by ambulatory cough monitoring device
Change in Awake Objective Cough Frequency at Week 4 Compared to Baseline Week 4 Objective cough frequency measured by ambulatory cough monitoring device
Change in the Leicester Cough Questionnaire (LCQ) at Week 2 Compared to Baseline Baseline to Week 2 The Leicester Cough Questionnaire (LCQ) is a 19 item questionnaire that assessed cough related quality of life. It has three domains (physical, psychological and social) and subjects were asked to complete it based on their experience in a recall period of 2 weeks. The total score range is 3 to 21 and domain scores each range from 1 to 7; a higher score indicated a better quality of life. Subjects completed the LCQ whilst in the clinic at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Leicester Cough Questionnaire (LCQ) at Week 4 Compared to Baseline Baseline to Week 4 The Leicester Cough Questionnaire (LCQ) is a 19 item questionnaire that assessed cough related quality of life. It has three domains (physical, psychological and social) and subjects were asked to complete it based on their experience in a recall period of 4 weeks. The total score range is 3 to 21 and domain scores each range from 1 to 7; a higher score indicated a better quality of life. Subjects completed the LCQ whilst in the clinic at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Leicester Cough Questionnaire (LCQ) at Week 8 Compared to Baseline Baseline to Week 8 The Leicester Cough Questionnaire (LCQ) is a 19 item questionnaire that assessed cough related quality of life. It has three domains (physical, psychological and social) and subjects were asked to complete it based on their experience in a recall period of 8 weeks. The total score range is 3 to 21 and domain scores each range from 1 to 7; a higher score indicated a better quality of life. Subjects completed the LCQ whilst in the clinic at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Leicester Cough Questionnaire (LCQ) at Week 12 Compared to Baseline Baseline to Week 12 The Leicester Cough Questionnaire (LCQ) is a 19 item questionnaire that assessed cough related quality of life. It has three domains (physical, psychological and social) and subjects were asked to complete it based on their experience in a recall period of 12 weeks. The total score range is 3 to 21 and domain scores each range from 1 to 7; a higher score indicated a better quality of life. Subjects completed the LCQ whilst in the clinic at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Day-time Baseline to Week 2 The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Day-time Baseline to Week 4 The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Day-time Baseline to Week 8 The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Day-time Baseline to Week 12 The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Night-time Baseline to Week 2 The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Night-time Baseline to Week 4 The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Night-time Baseline to Week 8 The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Night-time Baseline to Week 12 The cough VAS is a 100 mm scale on which subjects indicated their severity of cough over the previous 24 hours, both during the day-time and during night time separately. The VAS ranged from "no cough" (0 mm) on the left to "worst cough" (100 mm) on the right. Subjects completed the cough severity VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 2 Compared to Baseline Baseline to Week 2 The urge-to-cough VAS was a 100 mm scale on which subjects indicated their urge to cough over the previous 24 hours (day/awake time and night time combined). The VAS ranged from "no urge to cough" (0 mm) on the left to "severe urge to cough" (100 mm) on the right. Subjects completed the urge to cough VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 4 Compared to Baseline Baseline to Week 4 The urge-to-cough VAS was a 100 mm scale on which subjects indicated their urge to cough over the previous 24 hours (day/awake time and night time combined). The VAS ranged from "no urge to cough" (0 mm) on the left to "severe urge to cough" (100 mm) on the right. Subjects completed the urge to cough VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 8 Compared to Baseline Baseline to Week 8 The urge-to-cough VAS was a 100 mm scale on which subjects indicated their urge to cough over the previous 24 hours (day/awake time and night time combined). The VAS ranged from "no urge to cough" (0 mm) on the left to "severe urge to cough" (100 mm) on the right. Subjects completed the urge to cough VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 12 Compared to Baseline Baseline to Week 12 The urge-to-cough VAS was a 100 mm scale on which subjects indicated their urge to cough over the previous 24 hours (day/awake time and night time combined). The VAS ranged from "no urge to cough" (0 mm) on the left to "severe urge to cough" (100 mm) on the right. Subjects completed the urge to cough VAS at baseline/Day 1 (pre dose) and at Weeks 2, 4, 8, and 12.
Global Rating of Change in Cough Frequency at Week 2 Baseline to Week 2 In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
Global Rating of Change in Cough Frequency at Week 4 Baseline to Week 4 In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
Global Rating of Change in Cough Frequency at Week 8 Baseline to Week 8 In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
Global Rating of Change in Cough Frequency at Week 12 Baseline to Week 12 In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
Global Rating of Change in Cough Severity at Week 2 Baseline to Week 2 In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
Global Rating of Change in Cough Severity at Week 4 Baseline to Week 4 In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
Global Rating of Change in Cough Severity at Week 8 Baseline to Week 8 In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
Global Rating of Change in Cough Severity at Week 12 Baseline to Week 12 In the Global Rating of Change scale, subjects indicated if there had been a change in their symptoms (cough frequency and, separately, cough severity) since starting the IMP. Subjects responded with "worse", "about the same" or "better". If subjects indicated a change (either "worse" or "better") they then indicated on a 7 point scale the degree of change ranging from 1 (almost the same, hardly any change) to 7 (a very great deal changed). Subjects documented their Global Rating of Change in cough frequency and cough severity at Weeks 2, 4, 8, and 12.
Trial Locations
- Locations (66)
Study Site 22
🇺🇸Dallas, Texas, United States
Study Site 43
🇺🇸Los Angeles, California, United States
Study Site 10
🇺🇸Houston, Texas, United States
Study Site 47
🇬🇧Newcastle Upon Tyne, United Kingdom
Study Site 20
🇺🇸San Diego, California, United States
Study Site 33
🇺🇸Tampa, Florida, United States
Study Site 41
🇺🇸Minneapolis, Minnesota, United States
Study Site 37
🇺🇸Rochester, Minnesota, United States
Study Site 16
🇺🇸Las Vegas, Nevada, United States
Study Site 56
🇺🇸Cincinnati, Ohio, United States
Study Site 74
🇺🇸Oklahoma City, Oklahoma, United States
Study Site 49
🇺🇸San Antonio, Texas, United States
Study Site 58
🇺🇸Salt Lake City, Utah, United States
Study Site 15
🇺🇸Chandler, Arizona, United States
Study Site 52
🇺🇸Mission Viejo, California, United States
Study Site 36
🇺🇸Colorado Springs, Colorado, United States
Study Site 27
🇺🇸Missoula, Montana, United States
Study Site 34
🇺🇸Baltimore, Maryland, United States
Study Site 59
🇺🇸Jacksonville, Florida, United States
Study Site 12
🇺🇸Largo, Florida, United States
Study Site 60
🇺🇸Meridian, Idaho, United States
Study Site 57
🇺🇸Miami, Florida, United States
Study Site 39
🇺🇸Normal, Illinois, United States
Study Site 42
🇺🇸Edina, Minnesota, United States
Study Site 32
🇺🇸Rochester, New York, United States
Study Site 55
🇺🇸Charlotte, North Carolina, United States
Study Site 53
🇺🇸Charlotte, North Carolina, United States
Study Site 24
🇺🇸Charlotte, North Carolina, United States
Study Site 50
🇺🇸Gastonia, North Carolina, United States
Study Site 71
🇺🇸Raleigh, North Carolina, United States
Study Site 26
🇺🇸Tulsa, Oklahoma, United States
Study Site 29
🇬🇧Romford, Essex, United Kingdom
Study Site 23
🇺🇸Waco, Texas, United States
Study Site 38
🇺🇸East Providence, Rhode Island, United States
Study Site 21
🇺🇸Charleston, South Carolina, United States
Study Site 14
🇺🇸Bellingham, Washington, United States
Study Site 72
🇺🇸Charleston, South Carolina, United States
Study Site 19
🇺🇸Charlottesville, Virginia, United States
Study Site 35
🇺🇸Dallas, Texas, United States
Study Site 65
🇨🇦Québec, Quebec, Canada
Study Site 64
🇨🇦Trois-Rivières, Quebec, Canada
Study Site 66
🇨🇦Niagara Falls, Ontario, Canada
Study Site 93
🇬🇧Prescot, Merseyside, United Kingdom
Study Site 94
🇬🇧Blackpool, Lancashire, United Kingdom
Study Site 46
🇬🇧London, United Kingdom
Study Site 91
🇬🇧Manchester, United Kingdom
Study Site 17
🇬🇧Northwood, Middlesex, United Kingdom
Study Site 97
🇬🇧Cannock, Staffordshire, United Kingdom
Study Site 18
🇬🇧Manchester, United Kingdom
Study Site 96
🇬🇧Barnsley, South Yorkshire, United Kingdom
Study Site 45
🇬🇧Hull, United Kingdom
Study Site 92
🇬🇧Leeds, United Kingdom
Study Site 30
🇬🇧Leicester, United Kingdom
Study Site44
🇬🇧Oxford, United Kingdom
Study Site 62
🇺🇸Miami, Florida, United States
Study Site 11
🇺🇸Winter Park, Florida, United States
Study Site 54
🇺🇸Greensboro, North Carolina, United States
Study Site 68
🇺🇸Clearwater, Florida, United States
Study Site 25
🇺🇸Centennial, Colorado, United States
Study Site 28
🇺🇸San Jose, California, United States
Study Site 73
🇺🇸Mooresville, North Carolina, United States
Study Site 95
🇬🇧Stockton-on-Tees, Teesside, United Kingdom
Study Site 40
🇬🇧Belfast, Northern Ireland, United Kingdom
Study Site 31
🇬🇧North Shields, United Kingdom
Study Site 13
🇺🇸Greenfield, Wisconsin, United States
Study Site 48
🇺🇸Waterbury, Connecticut, United States