A Dose-ranging Study of Orvepitant in Patients With Chronic Refractory Cough

Phase 2

Completed

Conditions: Chronic Refractory Cough

Interventions: Drug: Orvepitant Maleate
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

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.

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 15
🇺🇸
Chandler, Arizona, United States
Study Site 43
🇺🇸
Los Angeles, California, United States
Study Site 52
🇺🇸
Mission Viejo, California, United States
Study Site 20
🇺🇸
San Diego, California, United States
Study Site 28
🇺🇸
San Jose, California, United States
Study Site 25
🇺🇸
Centennial, Colorado, United States
Study Site 36
🇺🇸
Colorado Springs, Colorado, United States
Study Site 48
🇺🇸
Waterbury, Connecticut, United States
Study Site 68
🇺🇸
Clearwater, Florida, United States
Study Site 59
🇺🇸
Jacksonville, Florida, United States
Scroll for more (56 remaining)
Study Site 15
🇺🇸Chandler, Arizona, United States