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

A Double-Blind, Randomized, Placebo Controlled Study of the Efficacy and Safety of Three Doses of Orvepitant in Subjects With Chronic Refractory Cough

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.

Study Overview

• Status: Completed
• Conditions: Chronic Refractory Cough
• Intervention / Treatment: Drug: Placebo; Drug: Orvepitant Maleate

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.

• Study Type: Interventional
• Enrollment (Actual): 315
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Niagara Falls, Ontario, Canada, L2G 1J4
      • Study Site 66
  • Quebec
    • Québec, Quebec, Canada, G1V 4W2
      • Study Site 65
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • Study Site 64
• United Kingdom
  • Hull, United Kingdom
    • Study Site 45
  • Leeds, United Kingdom, LS10 1DU
    • Study Site 92
  • Leicester, United Kingdom
    • Study site 30
  • London, United Kingdom
    • Study Site 46
  • Manchester, United Kingdom, M32 0UT
    • Study Site 91
  • Manchester, United Kingdom
    • Study site 18
  • Newcastle Upon Tyne, United Kingdom
    • Study Site 47
  • North Shields, United Kingdom
    • Study site 31
  • Oxford, United Kingdom
    • Study Site44
  • Essex
    • Romford, Essex, United Kingdom, RM1 3PJ
      • Study site 29
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY2 0JH
      • Study Site 94
  • Merseyside
    • Prescot, Merseyside, United Kingdom, L34 1BH
      • Study Site 93
  • Middlesex
    • Northwood, Middlesex, United Kingdom
      • Study site 17
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 7AB
      • Study Site 40
  • South Yorkshire
    • Barnsley, South Yorkshire, United Kingdom, S75 3DL
      • Study Site 96
  • Staffordshire
    • Cannock, Staffordshire, United Kingdom, WS11 0BN
      • Study Site 97
  • Teesside
    • Stockton-on-Tees, Teesside, United Kingdom, TS17 6EW
      • Study Site 95
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Study site 15
  • California
    • Los Angeles, California, United States, 90025
      • Study Site 43
    • Mission Viejo, California, United States, 92692
      • Study Site 52
    • San Diego, California, United States, 92108
      • Study Site 20
    • San Jose, California, United States, 95117
      • Study site 28
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Study site 25
    • Colorado Springs, Colorado, United States, 80907
      • Study Site 36
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Study Site 48
  • Florida
    • Clearwater, Florida, United States, 33765
      • Study Site 68
    • Jacksonville, Florida, United States, 32224
      • Study Site 59
    • Largo, Florida, United States, 33778
      • Study site 12
    • Miami, Florida, United States, 33060
      • Study Site 62
    • Miami, Florida, United States, 33186
      • Study Site 57
    • Tampa, Florida, United States, 33613
      • Study Site 33
    • Winter Park, Florida, United States, 32789
      • Study site 11
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Study Site 60
  • Illinois
    • Normal, Illinois, United States, 61761
      • Study Site 39
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • Study Site 34
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Study Site 42
    • Minneapolis, Minnesota, United States, 55402
      • Study Site 41
    • Rochester, Minnesota, United States, 55905
      • Study Site 37
  • Montana
    • Missoula, Montana, United States, 59808
      • Study site 27
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Study site 16
  • New York
    • Rochester, New York, United States, 14618
      • Study Site 32
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Study Site 55
    • Charlotte, North Carolina, United States, 28207
      • Study site 24
    • Charlotte, North Carolina, United States, 29732
      • Study Site 53
    • Gastonia, North Carolina, United States, 28054
      • Study Site 50
    • Greensboro, North Carolina, United States, 27403
      • Study Site 54
    • Mooresville, North Carolina, United States, 28117
      • Study Site 73
    • Raleigh, North Carolina, United States, 27612
      • Study Site 71
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Study Site 56
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73131
      • Study Site 74
    • Tulsa, Oklahoma, United States, 74136
      • Study Site 26
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Study Site 38
  • South Carolina
    • Charleston, South Carolina, United States, 29420
      • Study site 21
    • Charleston, South Carolina, United States, 29464
      • Study Site 72
  • Texas
    • Dallas, Texas, United States, 75231
      • Study site 22
    • Dallas, Texas, United States, 75231
      • Study Site 35
    • Houston, Texas, United States, 77074
      • Study site 10
    • San Antonio, Texas, United States, 78229
      • Study Site 49
    • Waco, Texas, United States, 76712
      • Study site 23
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Study Site 58
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Study site 19
  • Washington
    • Bellingham, Washington, United States, 98225
      • Study site 14
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Study site 13

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orvepitant 10mg; Orvepitant 10mg tablet, once daily for 12 weeks	Drug: Orvepitant Maleate; Tablet, once daily, oral
Experimental: Orvepitant 20mg; Orvepitant 20mg tablet, once daily for 12 weeks	Drug: Orvepitant Maleate; Tablet, once daily, oral
Experimental: Orvepitant 30mg; Orvepitant 30mg tablet, once daily for 12 weeks	Drug: Orvepitant Maleate; Tablet, once daily, oral
Placebo Comparator: Placebo; Placebo to match tablet, once daily for 12 weeks	Drug: Placebo; Tablet, once daily, oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in Awake Objective Cough Frequency	Objective cough frequency measured by ambulatory cough monitoring device	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Awake Objective Cough Frequency at Week 2 Compared to Baseline	Objective cough frequency measured by ambulatory cough monitoring device	Baseline to Week 2
Change in Awake Objective Cough Frequency at Week 4 Compared to Baseline	Objective cough frequency measured by ambulatory cough monitoring device	Week 4
Change in the Leicester Cough Questionnaire (LCQ) at Week 2 Compared to Baseline	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.	Baseline to Week 2
Change in the Leicester Cough Questionnaire (LCQ) at Week 4 Compared to Baseline	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.	Baseline to Week 4
Change in the Leicester Cough Questionnaire (LCQ) at Week 8 Compared to Baseline	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.	Baseline to Week 8
Change in the Leicester Cough Questionnaire (LCQ) at Week 12 Compared to Baseline	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.	Baseline to Week 12
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Day-time	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.	Baseline to Week 2
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Day-time	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.	Baseline to Week 4
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Day-time	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.	Baseline to Week 8
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Day-time	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.	Baseline to Week 12
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Night-time	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.	Baseline to Week 2
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Night-time	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.	Baseline to Week 4
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Night-time	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.	Baseline to Week 8
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Night-time	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.	Baseline to Week 12
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 2 Compared to Baseline	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.	Baseline to Week 2
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 4 Compared to Baseline	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.	Baseline to Week 4
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 8 Compared to Baseline	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.	Baseline to Week 8
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 12 Compared to Baseline	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.	Baseline to Week 12
Global Rating of Change in Cough Frequency at 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.	Baseline to Week 2
Global Rating of Change in Cough Frequency at 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.	Baseline to Week 4
Global Rating of Change in Cough Frequency at 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.	Baseline to Week 8
Global Rating of Change in Cough Frequency at 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.	Baseline to Week 12
Global Rating of Change in Cough Severity at 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.	Baseline to Week 2
Global Rating of Change in Cough Severity at 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.	Baseline to Week 4
Global Rating of Change in Cough Severity at 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.	Baseline to Week 8
Global Rating of Change in Cough Severity at 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.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Nerre Therapeutics Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2017
• Primary Completion (Actual): January 14, 2019
• Study Completion (Actual): January 24, 2019

Study Registration Dates

• First Submitted: December 6, 2016
• First Submitted That Met QC Criteria: December 12, 2016
• First Posted (Estimate): December 15, 2016

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Maleic acid
• Other Study ID Numbers: VOLCANO-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No