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Phase 2 N=315 Randomized Quadruple-blind Treatment

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

Chronic Refractory Cough

Enrolled (actual)
315
Serious AEs
1.9%
Results posted
Apr 2022
Primary outcome: Primary: Change From Baseline to Week 12 in Awake Objective Cough Frequency — -0.185; -0.192; -0.271; -0.243 coughs per hour (log transformed) — p=0.324

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Orvepitant Maleate (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Nerre Therapeutics Ltd.
Primary completion
Jan 2019

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline to Week 12 in Awake Objective Cough Frequency
-0.185; -0.192; -0.271; -0.243 0.324
SECONDARY
Change in Awake Objective Cough Frequency at Week 2 Compared to Baseline
-0.180; -0.181; -0.215; -0.139 0.482
SECONDARY
Change in Awake Objective Cough Frequency at Week 4 Compared to Baseline
-0.188; -0.231; -0.211; -0.169 0.992
SECONDARY
Change in the Leicester Cough Questionnaire (LCQ) at Week 2 Compared to Baseline
2.41; 2.37; 2.93; 1.24 0.042 sig
SECONDARY
Change in the Leicester Cough Questionnaire (LCQ) at Week 4 Compared to Baseline
2.50; 2.15; 2.98; 1.61 0.250
SECONDARY
Change in the Leicester Cough Questionnaire (LCQ) at Week 8 Compared to Baseline
2.78; 2.19; 2.82; 1.34 0.038 sig
SECONDARY
Change in the Leicester Cough Questionnaire (LCQ) at Week 12 Compared to Baseline
2.38; 2.09; 3.23; 1.50 0.258
SECONDARY
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Day-time
-17.7; -10.5; -13.5; -6.3 0.008 sig
SECONDARY
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Day-time
-17.9; -9.4; -15.9; -7.8 0.026 sig
SECONDARY
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Day-time
-21.0; -9.9; -18.6; -8.2 0.006 sig
SECONDARY
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Day-time
-18.8; -11.6; -20.1; -10.6 0.103
SECONDARY
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 2 Compared to Baseline - Night-time
-12.8; -7.8; -6.2; -3.9 0.004 sig
SECONDARY
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 4 Compared to Baseline - Night-time
-10.1; -7.9; -5.8; -2.7 0.019 sig
SECONDARY
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 8 Compared to Baseline - Night-time
-11.5; -6.8; -9.8; -2.2 0.006 sig
SECONDARY
Change in the Cough Severity Visual Analogue Scale (VAS) at Week 12 Compared to Baseline - Night-time
-8.9; -7.1; -9.6; -1.5 0.027 sig
SECONDARY
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 2 Compared to Baseline
-20.8; -12.0; -13.8; -7.0 <0.001 sig
SECONDARY
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 4 Compared to Baseline
-19.0; -12.0; -17.3; -8.8 0.027 sig
SECONDARY
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 8 Compared to Baseline
-23.8; -14.5; -19.7; -11.0 0.008 sig
SECONDARY
Change in the Urge-to-cough Visual Analogue Scale (VAS) at Week 12 Compared to Baseline
-23.7; -12.6; -22.9; -11.8 0.018 sig
SECONDARY
Global Rating of Change in Cough Frequency at Week 2
4; 10; 5; 11; 35; 37 0.004 sig
SECONDARY
Global Rating of Change in Cough Frequency at Week 4
9; 8; 6; 12; 32; 36 0.401
SECONDARY
Global Rating of Change in Cough Frequency at Week 8
11; 17; 10; 20; 22; 31 0.002 sig
SECONDARY
Global Rating of Change in Cough Frequency at Week 12
7; 13; 7; 13; 32; 33 0.158
SECONDARY
Global Rating of Change in Cough Severity at Week 2
7; 8; 4; 12; 33; 39 0.01 sig
SECONDARY
Global Rating of Change in Cough Severity at Week 4
9; 7; 7; 14; 32; 43 0.309
SECONDARY
Global Rating of Change in Cough Severity at Week 8
8; 12; 6; 15; 26; 36 0.003 sig
SECONDARY
Global Rating of Change in Cough Severity at Week 12
5; 15; 8; 16; 38; 33 0.100

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.

Eligibility Criteria

Key Inclusion Criteria

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

Key Exclusion Criteria

  • Subjects with respiratory tract infection ( 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02993822). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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