Chronic Refractory Cough
Conditions
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.
Interventions
Tablet, once daily, oral
DRUGPlacebo
Tablet, once daily, oral
Sponsors
Nerre Therapeutics Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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. |
Countries
Canada, United Kingdom, United States
Participant flow
Recruitment details
The first subject was enrolled (screened and consented) on 22-May-2017; the first subject was randomised on 31-Jan-2017. The last subject was enrolled on 28-Sep-2018. The last subject last visit (study completion) was 24-Jan-2019. Subjects were recruited from a mixture of specialised standalone clinics and clinics within hospitals.
Pre-assignment details
Screening details: 488 subjects were screened, of whom 315 (64.5%) completed screening and were randomised. Screening failures occurred due to not meeting inclusion criteria (74 subjects \[15.2%\]) or exclusion criteria (79 subjects \[16.2%\]), withdrawal of consent (nine \[1.8%\] subjects) and AEs (2 \[0.4%\] subjects). All other reasons reported in individual subjects.
Participants by arm
| Arm | Count |
|---|---|
| Orvepitant 10mg Orvepitant 10mg tablet, once daily for 12 weeks
Orvepitant Maleate: Tablet, once daily, oral | 79 |
| Orvepitant 20mg Orvepitant 20mg tablet, once daily for 12 weeks
Orvepitant Maleate: Tablet, once daily, oral | 78 |
| Orvepitant 30mg Orvepitant 30mg tablet, once daily for 12 weeks
Orvepitant Maleate: Tablet, once daily, oral | 79 |
| Placebo Placebo to match tablet, once daily for 12 weeks
Placebo: Tablet, once daily, oral | 79 |
| Total | 315 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 7 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 |
| Overall Study | Unable to attend follow-up due to illness | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 2 | 2 | 3 |
Baseline characteristics
| Characteristic | Orvepitant 10mg | Orvepitant 20mg | Orvepitant 30mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 33 Participants | 34 Participants | 23 Participants | 42 Participants | 132 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 44 Participants | 56 Participants | 37 Participants | 183 Participants |
| Age, Continuous | 62.29 years STANDARD_DEVIATION 9.85 | 59.86 years STANDARD_DEVIATION 13.173 | 59.47 years STANDARD_DEVIATION 10.02 | 62.24 years STANDARD_DEVIATION 11.815 | 60.97 years STANDARD_DEVIATION 11.313 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants | 74 Participants | 77 Participants | 74 Participants | 299 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 3 Participants | 1 Participants | 1 Participants | 10 Participants |
| Region of Enrollment Europe | 28 participants | 29 participants | 28 participants | 28 participants | 113 participants |
| Region of Enrollment North America | 51 participants | 49 participants | 51 participants | 51 participants | 202 participants |
| Sex: Female, Male Female | 65 Participants | 69 Participants | 60 Participants | 59 Participants | 253 Participants |
| Sex: Female, Male Male | 14 Participants | 9 Participants | 19 Participants | 20 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 79 | 0 / 78 | 0 / 79 | 0 / 79 |
| other Total, other adverse events | 63 / 79 | 48 / 78 | 53 / 79 | 40 / 79 |
| serious Total, serious adverse events | 1 / 79 | 1 / 78 | 3 / 79 | 1 / 79 |
Outcome results
Primary
Change From Baseline to Week 12 in Awake Objective Cough Frequency
Objective cough frequency measured by ambulatory cough monitoring device
Time frame: Baseline to Week 12
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change From Baseline to Week 12 in Awake Objective Cough Frequency | -0.185 coughs per hour (log transformed) | Standard Deviation 0.3258 |
| Orvepitant 20mg | Change From Baseline to Week 12 in Awake Objective Cough Frequency | -0.192 coughs per hour (log transformed) | Standard Deviation 0.3405 |
| Orvepitant 30mg | Change From Baseline to Week 12 in Awake Objective Cough Frequency | -0.271 coughs per hour (log transformed) | Standard Deviation 0.4055 |
| Placebo | Change From Baseline to Week 12 in Awake Objective Cough Frequency | -0.243 coughs per hour (log transformed) | Standard Deviation 0.3225 |
Comparison: Change from baseline to each visit (Week 2, Week 4 and Week 12) in log transformed awake objective cough frequency was analysed using a mixed model for repeated measures (MMRM) with restricted maximum likelihood (REML) estimation. The treatment effect at Week 12 was estimated using the ratio of geometric means (i.e. the difference between the treatments least squares means \[adjusted means\] on the log scale, back transformed to the original scale).p-value: 0.32495% CI: [0.88, 1.49]Mixed model repeated measures
Comparison: Change from baseline to each visit (Week 2, Week 4 and Week 12) in log transformed awake objective cough frequency was analysed using a mixed model for repeated measures (MMRM) with restricted maximum likelihood (REML) estimation. The treatment effect at Week 12 was estimated using the ratio of geometric means (i.e. the difference between the treatments least squares means \[adjusted means\] on the log scale, back transformed to the original scale).p-value: 0.33295% CI: [0.88, 1.48]Mixed model repeated measures
Comparison: Change from baseline to each visit (Week 2, Week 4 and Week 12) in log transformed awake objective cough frequency was analysed using a mixed model for repeated measures (MMRM) with restricted maximum likelihood (REML) estimation. The treatment effect at Week 12 was estimated using the ratio of geometric means (i.e. the difference between the treatments least squares means \[adjusted means\] on the log scale, back transformed to the original scale).p-value: 0.53195% CI: [0.71, 1.2]Mixed model repeated measures
Secondary
Change in Awake Objective Cough Frequency at Week 2 Compared to Baseline
Objective cough frequency measured by ambulatory cough monitoring device
Time frame: Baseline to Week 2
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in Awake Objective Cough Frequency at Week 2 Compared to Baseline | -0.180 coughs per hour (log transformed) | Standard Deviation 0.2791 |
| Orvepitant 20mg | Change in Awake Objective Cough Frequency at Week 2 Compared to Baseline | -0.181 coughs per hour (log transformed) | Standard Deviation 0.3142 |
| Orvepitant 30mg | Change in Awake Objective Cough Frequency at Week 2 Compared to Baseline | -0.215 coughs per hour (log transformed) | Standard Deviation 0.2515 |
| Placebo | Change in Awake Objective Cough Frequency at Week 2 Compared to Baseline | -0.139 coughs per hour (log transformed) | Standard Deviation 0.2892 |
Comparison: Change from baseline to each visit (Week 2, Week 4 and Week 12) in log transformed awake objective cough frequency was analysed using a mixed model for repeated measures (MMRM) with restricted maximum likelihood (REML) estimation. The treatment effect at Week 12 was estimated using the ratio of geometric means (i.e. the difference between the treatments least squares means \[adjusted means\] on the log scale, back transformed to the original scale).p-value: 0.48295% CI: [0.75, 1.15]Mixed model repeated measures
Comparison: Change from baseline to each visit (Week 2, Week 4 and Week 12) in log transformed awake objective cough frequency was analysed using a mixed model for repeated measures (MMRM) with restricted maximum likelihood (REML) estimation. The treatment effect at Week 12 was estimated using the ratio of geometric means (i.e. the difference between the treatments least squares means \[adjusted means\] on the log scale, back transformed to the original scale).p-value: 0.4695% CI: [0.75, 1.14]Mixed model repeated measures
Comparison: Change from baseline to each visit (Week 2, Week 4 and Week 12) in log transformed awake objective cough frequency was analysed using a mixed model for repeated measures (MMRM) with restricted maximum likelihood (REML) estimation. The treatment effect at Week 12 was estimated using the ratio of geometric means (i.e. the difference between the treatments least squares means \[adjusted means\] on the log scale, back transformed to the original scale).p-value: 0.14495% CI: [0.69, 1.06]Mixed model repeated measures
Secondary
Change in Awake Objective Cough Frequency at Week 4 Compared to Baseline
Objective cough frequency measured by ambulatory cough monitoring device
Time frame: Week 4
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in Awake Objective Cough Frequency at Week 4 Compared to Baseline | -0.188 coughs per hour (log transformed) | Standard Deviation 0.3292 |
| Orvepitant 20mg | Change in Awake Objective Cough Frequency at Week 4 Compared to Baseline | -0.231 coughs per hour (log transformed) | Standard Deviation 0.3665 |
| Orvepitant 30mg | Change in Awake Objective Cough Frequency at Week 4 Compared to Baseline | -0.211 coughs per hour (log transformed) | Standard Deviation 0.2994 |
| Placebo | Change in Awake Objective Cough Frequency at Week 4 Compared to Baseline | -0.169 coughs per hour (log transformed) | Standard Deviation 0.2699 |
Comparison: Change from baseline to each visit (Week 2, Week 4 and Week 12) in log transformed awake objective cough frequency was analysed using a mixed model for repeated measures (MMRM) with restricted maximum likelihood (REML) estimation. The treatment effect at Week 12 was estimated using the ratio of geometric means (i.e. the difference between the treatments least squares means \[adjusted means\] on the log scale, back transformed to the original scale).p-value: 0.99295% CI: [0.78, 1.27]Mixed model repeated measures
Comparison: Change from baseline to each visit (Week 2, Week 4 and Week 12) in log transformed awake objective cough frequency was analysed using a mixed model for repeated measures (MMRM) with restricted maximum likelihood (REML) estimation. The treatment effect at Week 12 was estimated using the ratio of geometric means (i.e. the difference between the treatments least squares means \[adjusted means\] on the log scale, back transformed to the original scale).p-value: 0.38795% CI: [0.71, 1.14]Mixed model repeated measures
Comparison: Change from baseline to each visit (Week 2, Week 4 and Week 12) in log transformed awake objective cough frequency was analysed using a mixed model for repeated measures (MMRM) with restricted maximum likelihood (REML) estimation. The treatment effect at Week 12 was estimated using the ratio of geometric means (i.e. the difference between the treatments least squares means \[adjusted means\] on the log scale, back transformed to the original scale).p-value: 0.695% CI: [0.74, 1.19]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 12
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Day-time | -18.8 Score | Standard Deviation 31.27 |
| Orvepitant 20mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Day-time | -11.6 Score | Standard Deviation 27.33 |
| Orvepitant 30mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Day-time | -20.1 Score | Standard Deviation 29.33 |
| Placebo | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Day-time | -10.6 Score | Standard Deviation 24.46 |
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.10395% CI: [-15.3, 1.4]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.54695% CI: [-10.6, 5.6]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.03495% CI: [-17.2, -0.7]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 12
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Night-time | -8.9 Score | Standard Deviation 35.99 |
| Orvepitant 20mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Night-time | -7.1 Score | Standard Deviation 26.88 |
| Orvepitant 30mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Night-time | -9.6 Score | Standard Deviation 30.24 |
| Placebo | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Night-time | -1.5 Score | Standard Deviation 33.74 |
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.02795% CI: [-18.9, -1.2]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.14795% CI: [-14.9, 2.2]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.04695% CI: [-17.6, -0.1]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 2
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Day-time | -17.7 Score | Standard Deviation 26.06 |
| Orvepitant 20mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Day-time | -10.5 Score | Standard Deviation 27.78 |
| Orvepitant 30mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Day-time | -13.5 Score | Standard Deviation 22.93 |
| Placebo | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Day-time | -6.3 Score | Standard Deviation 19.24 |
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.00895% CI: [-16.6, -2.5]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.19895% CI: [-11.4, 2.4]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.05595% CI: [-13.7, 0.1]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 2
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Night-time | -12.8 Score | Standard Deviation 28.96 |
| Orvepitant 20mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Night-time | -7.8 Score | Standard Deviation 26.76 |
| Orvepitant 30mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Night-time | -6.2 Score | Standard Deviation 24.97 |
| Placebo | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Night-time | -3.9 Score | Standard Deviation 27.62 |
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.00495% CI: [-18.8, -3.6]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.28295% CI: [-11.5, 3.4]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.39895% CI: [-10.7, 4.3]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 4
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Day-time | -17.9 Score | Standard Deviation 27.11 |
| Orvepitant 20mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Day-time | -9.4 Score | Standard Deviation 26.76 |
| Orvepitant 30mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Day-time | -15.9 Score | Standard Deviation 25.02 |
| Placebo | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Day-time | -7.8 Score | Standard Deviation 22.36 |
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.02695% CI: [-16.3, -1.1]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.57195% CI: [-9.6, 5.3]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.04395% CI: [-15.2, -0.3]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 4
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Night-time | -10.1 Score | Standard Deviation 32.87 |
| Orvepitant 20mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Night-time | -7.9 Score | Standard Deviation 27.52 |
| Orvepitant 30mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Night-time | -5.8 Score | Standard Deviation 27.96 |
| Placebo | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Night-time | -2.7 Score | Standard Deviation 27.99 |
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.01995% CI: [-18.3, -1.7]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.1795% CI: [-13.7, 2.4]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.38495% CI: [-11.7, 4.5]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 8
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Day-time | -21.0 Score | Standard Deviation 30.37 |
| Orvepitant 20mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Day-time | -9.9 Score | Standard Deviation 29.57 |
| Orvepitant 30mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Day-time | -18.6 Score | Standard Deviation 27.24 |
| Placebo | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Day-time | -8.2 Score | Standard Deviation 23.58 |
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.00695% CI: [-19.7, -3.3]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.43595% CI: [-11.1, 4.8]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.02295% CI: [-17.4, -1.4]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 8
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Night-time | -11.5 Score | Standard Deviation 32.65 |
| Orvepitant 20mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Night-time | -6.8 Score | Standard Deviation 29.07 |
| Orvepitant 30mg | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Night-time | -9.8 Score | Standard Deviation 28.73 |
| Placebo | Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Night-time | -2.2 Score | Standard Deviation 28.95 |
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.00695% CI: [-20, -3.3]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.22295% CI: [-13, 3]Mixed model repeated measures
Comparison: Change in the Cough Severity VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in Cough Severity VAS was analysed using a MMRM with REML estimation.p-value: 0.05895% CI: [-16, 0.3]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 12
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 12 Compared to Baseline | 2.38 Total score | Standard Deviation 3.609 |
| Orvepitant 20mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 12 Compared to Baseline | 2.09 Total score | Standard Deviation 3.736 |
| Orvepitant 30mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 12 Compared to Baseline | 3.23 Total score | Standard Deviation 4.007 |
| Placebo | Change in the Leicester Cough Questionnaire (LCQ) at Week 12 Compared to Baseline | 1.50 Total score | Standard Deviation 3.586 |
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.25895% CI: [-0.5, 1.9]Mixed model repeated measures
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.24395% CI: [-0.5, 1.8]Mixed model repeated measures
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.00995% CI: [0.4, 2.8]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 2
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 2 Compared to Baseline | 2.41 Total score | Standard Deviation 3.309 |
| Orvepitant 20mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 2 Compared to Baseline | 2.37 Total score | Standard Deviation 3.252 |
| Orvepitant 30mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 2 Compared to Baseline | 2.93 Total score | Standard Deviation 3.01 |
| Placebo | Change in the Leicester Cough Questionnaire (LCQ) at Week 2 Compared to Baseline | 1.24 Total score | Standard Deviation 2.714 |
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.04295% CI: [0, 2]Mixed model repeated measures
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.02695% CI: [0.1, 2]Mixed model repeated measures
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.00395% CI: [0.5, 2.4]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 4
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 4 Compared to Baseline | 2.50 Total score | Standard Deviation 3.416 |
| Orvepitant 20mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 4 Compared to Baseline | 2.15 Total score | Standard Deviation 3.49 |
| Orvepitant 30mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 4 Compared to Baseline | 2.98 Total score | Standard Deviation 3.163 |
| Placebo | Change in the Leicester Cough Questionnaire (LCQ) at Week 4 Compared to Baseline | 1.61 Total score | Standard Deviation 3.132 |
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.2595% CI: [-0.4, 1.7]Mixed model repeated measures
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.32595% CI: [-0.5, 1.5]Mixed model repeated measures
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.02995% CI: [0.1, 2.2]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 8
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 8 Compared to Baseline | 2.78 Total score | Standard Deviation 3.535 |
| Orvepitant 20mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 8 Compared to Baseline | 2.19 Total score | Standard Deviation 3.602 |
| Orvepitant 30mg | Change in the Leicester Cough Questionnaire (LCQ) at Week 8 Compared to Baseline | 2.82 Total score | Standard Deviation 3.96 |
| Placebo | Change in the Leicester Cough Questionnaire (LCQ) at Week 8 Compared to Baseline | 1.34 Total score | Standard Deviation 3.222 |
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.03895% CI: [0.1, 2.3]Mixed model repeated measures
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.11895% CI: [-0.2, 2]Mixed model repeated measures
Comparison: The change from baseline in LCQ total score and the three domain scores was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline.~The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in LCQ total score and the three domain scores was analysed using a MMRM with REML estimation.p-value: 0.02595% CI: [0.2, 2.4]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 12
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 12 Compared to Baseline | -23.7 Score | Standard Deviation 27.3 |
| Orvepitant 20mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 12 Compared to Baseline | -12.6 Score | Standard Deviation 28.57 |
| Orvepitant 30mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 12 Compared to Baseline | -22.9 Score | Standard Deviation 28.43 |
| Placebo | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 12 Compared to Baseline | -11.8 Score | Standard Deviation 26.5 |
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.01895% CI: [-18.4, -1.8]Mixed model repeated measures
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.68295% CI: [-9.8, 6.4]Mixed model repeated measures
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.00595% CI: [-20, -3.6]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 2
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 2 Compared to Baseline | -20.8 Score | Standard Deviation 24.59 |
| Orvepitant 20mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 2 Compared to Baseline | -12.0 Score | Standard Deviation 25.09 |
| Orvepitant 30mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 2 Compared to Baseline | -13.8 Score | Standard Deviation 22.03 |
| Placebo | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 2 Compared to Baseline | -7.0 Score | Standard Deviation 20.35 |
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: <0.00195% CI: [-19.5, -5.5]Mixed model repeated measures
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.11495% CI: [-12.4, 1.3]Mixed model repeated measures
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.05695% CI: [-13.7, 0.2]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 4
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 4 Compared to Baseline | -19.0 Score | Standard Deviation 26.93 |
| Orvepitant 20mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 4 Compared to Baseline | -12.0 Score | Standard Deviation 26.67 |
| Orvepitant 30mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 4 Compared to Baseline | -17.3 Score | Standard Deviation 24.73 |
| Placebo | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 4 Compared to Baseline | -8.8 Score | Standard Deviation 24.26 |
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.02795% CI: [-16.8, -1]Mixed model repeated measures
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.35795% CI: [-11.3, 4.1]Mixed model repeated measures
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.03195% CI: [-16.2, -0.8]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 8
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orvepitant 10mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 8 Compared to Baseline | -23.8 Score | Standard Deviation 28 |
| Orvepitant 20mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 8 Compared to Baseline | -14.5 Score | Standard Deviation 27.55 |
| Orvepitant 30mg | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 8 Compared to Baseline | -19.7 Score | Standard Deviation 26.8 |
| Placebo | Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 8 Compared to Baseline | -11.0 Score | Standard Deviation 24.78 |
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.00895% CI: [-19.2, -2.9]Mixed model repeated measures
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.32195% CI: [-11.8, 3.9]Mixed model repeated measures
Comparison: Change in the urge-to-cough VAS was summarised by treatment group and visit (Weeks 2, 4, 8 and 12) in terms of absolute values and changes from baseline. The effect of treatment in terms of the change from baseline to each scheduled visit (Week 2, Week 4, Week 8 and Week 12) in urge-to cough VAS was analysed using a MMRM with REML estimation.p-value: 0.04795% CI: [-16, -0.1]Mixed model repeated measures
Secondary
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.
Time frame: Baseline to Week 12
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 12 | Worse | 7 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 12 | Better | 28 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 12 | About the same | 32 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 12 | Worse | 13 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 12 | Better | 28 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 12 | About the same | 33 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 12 | About the same | 31 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 12 | Worse | 7 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 12 | Better | 29 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 12 | About the same | 37 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 12 | Worse | 13 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 12 | Better | 24 Participants |
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.158Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.597Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.124Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline to Week 2
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 2 | Better | 34 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 2 | Worse | 4 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 2 | About the same | 35 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 2 | Better | 30 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 2 | Worse | 10 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 2 | About the same | 37 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 2 | Better | 37 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 2 | Worse | 5 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 2 | About the same | 34 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 2 | About the same | 44 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 2 | Better | 19 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 2 | Worse | 11 Participants |
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.004Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.134Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.003Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline to Week 4
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 4 | Worse | 9 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 4 | Better | 28 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 4 | About the same | 32 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 4 | Worse | 8 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 4 | Better | 32 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 4 | About the same | 36 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 4 | About the same | 37 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 4 | Worse | 6 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 4 | Better | 31 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 4 | Worse | 12 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 4 | Better | 25 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 4 | About the same | 39 Participants |
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.401Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.175Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.126Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline to Week 8
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 8 | Worse | 11 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 8 | Better | 34 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Frequency at Week 8 | About the same | 22 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 8 | Worse | 17 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 8 | Better | 27 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Frequency at Week 8 | About the same | 31 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 8 | About the same | 37 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 8 | Worse | 10 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Frequency at Week 8 | Better | 25 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 8 | Worse | 20 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 8 | Better | 17 Participants |
| Placebo | Global Rating of Change in Cough Frequency at Week 8 | About the same | 38 Participants |
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.002Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.144Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.025Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline to Week 12
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 12 | Worse | 5 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 12 | Better | 24 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 12 | About the same | 38 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 12 | Worse | 15 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 12 | Better | 26 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 12 | About the same | 33 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 12 | About the same | 30 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 12 | Worse | 8 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 12 | Better | 29 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 12 | Worse | 16 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 12 | Better | 22 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 12 | About the same | 36 Participants |
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.1Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.557Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.054Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline to Week 2
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 2 | Worse | 7 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 2 | Better | 33 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 2 | About the same | 33 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 2 | Worse | 8 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 2 | Better | 30 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 2 | About the same | 39 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 2 | About the same | 35 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 2 | Worse | 4 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 2 | Better | 37 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 2 | Worse | 12 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 2 | Better | 18 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 2 | About the same | 44 Participants |
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.01Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.049Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.001Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline to Week 4
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 4 | Worse | 9 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 4 | Better | 28 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 4 | About the same | 32 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 4 | Worse | 7 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 4 | Better | 26 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 4 | About the same | 43 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 4 | About the same | 31 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 4 | Worse | 7 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 4 | Better | 36 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 4 | Worse | 14 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 4 | Better | 25 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 4 | About the same | 37 Participants |
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.309Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.387Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.025Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline to Week 8
Population: The number of participants analyzed differs from the overall subject disposition as it includes only participants with data available for the comparison (i.e. some participants have missing data).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 8 | Worse | 8 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 8 | About the same | 26 Participants |
| Orvepitant 10mg | Global Rating of Change in Cough Severity at Week 8 | Better | 33 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 8 | Better | 27 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 8 | About the same | 36 Participants |
| Orvepitant 20mg | Global Rating of Change in Cough Severity at Week 8 | Worse | 12 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 8 | Worse | 6 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 8 | About the same | 35 Participants |
| Orvepitant 30mg | Global Rating of Change in Cough Severity at Week 8 | Better | 31 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 8 | Better | 18 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 8 | About the same | 42 Participants |
| Placebo | Global Rating of Change in Cough Severity at Week 8 | Worse | 15 Participants |
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.003Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.152Cochran-Mantel-Haenszel
Comparison: The Global Rating of Change responses were summarised by treatment group and visit (Weeks 2, 4, 8 and 12) as categorical endpoints (worse, about the same and better). Pairwise comparisons were performed using the Cochran Mantel Haenszel test stratified by region using modified ridit scores (row mean scores differ).p-value: 0.004Cochran-Mantel-Haenszel