Chronic treatment-refractory cough MedDRA version: 17.1 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000004855
Conditions
Interventions
Product Name: Orvepitant
Product Code: GW823296
Pharmaceutical Form: Tablet
INN or Proposed INN: Orvepitant
CAS Number: 579475-24-4
Sponsors
NeRRe Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male and female subjects 18-75 years of age • Able to understand and comply with the requirements of the study and sign Informed Consent forms. • Females must be non-pregnant and non-lactating with no intention of pregnancy during study treatment • WOCP (not >1 year post-menopausal) must have a negative blood serum pregnancy test performed at the Screening visit and agree to use one of the following acceptable birth control methods: o Surgical sterilization of either the female subject in study (e.g., bilateral tubal ligation) or of her male partner (vasectomy with documented azoospermia) if he is the sole partner of that subject o Established hormonal contraception (implantable, patch, oral or intramuscular [IM]) administered for at least one month prior to study medication administration o An intrauterine device (IUD) or intrauterine system (IUS) with failure rate of less than 1% per year inserted by qualified physician at least one month prior to study medication administration o Double barrier method: condom and occlusive cap (diaphragm) with spermicidal foam/ gel/ film/ cream/ pessary • No clinically significant abnormal chest radiology in the opinion of the Investigator • Lung function defined by both the FEV1 and FVC >70% predicted, measured using spirometry • Diagnosis of chronic treatment-refractory cough based on a minimum of >3 months of symptoms. Chronic treatment-refractory cough (also called chronic idiopathic cough or chronic treatment-resistant cough), defined as a cough for which either no objective evidence of an underlying trigger can be determined after routine clinical investigation (idiopathic) or a cough that did not respond to standard treatment for identified underlying triggers (treatment-resistant). • A daytime cough frequency of >3 and a maximum of =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: • Subjects with recent respiratory tract infection (10 pack years • Treatment with Angiotensin Converting Enzyme (ACE) inhibitors within 3 months of study-start • Current drug or alcohol abuse • Uncontrolled hypertension (i.e., > 150/100 mmHg despite adequate medical therapy) • Recent myocardial infarction, or history of congestive cardiac failure. • Subjects with prior renal transplant, current renal dialysis, with creatinine clearance 1.5 times upper limit of normal reference ranges (after adjustment for age). • The use of opioids, anticonvulsants or tricyclic antidepressants because these may affect cough reflex sensitivity. Subjects currently taking drugs in these classes for chronic cough must have them discontinued at least 2 weeks prior to entry into the study. • Participation in any clinical research study evaluating another investigational drug or therapy within 30 days or within 5 half-lives (whichever is longer), of the investigational drug prior to consenting to study entry. If the subject is in an observational clinical study no washout is required. • Subjects receiving aprepitant (Emend®) or fosaprepitant (Ivemend®), NK-1 antagonists licensed as anti-emetics within 4 weeks of the Screening visit • Subjects who, in the opinion of the Investigator, should not participate in the study for any other reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the change in objectively recorded daytime cough frequency in chronic treatment-refractory cough patients at Week 4 after treatment with orvepitant (30 mg given once daily [od], orally).; Secondary Objective: • To evaluate the change in objectively recorded daytime cough frequency in chronic treatment-refractory cough patients at Week 1 after treatment with orvepitant and at Follow-up at Week 8. • To evaluate the change in objectively recorded night-time cough frequency in chronic treatment-refractory cough patients at Week 1 and Week 4 after treatment with orvepitant and at Follow-up at Week 8. • To evaluate the change in the Cough-specific Quality of Life Questionnaire (CQLQ) score at Weeks 1 and 4 after treatment with orvepitant and at Follow-up at Week 8. • To record the Global Rating of Change for Cough Frequency and Severity at Weeks 1 & 4 after treatment with orvepitant and at Follow-up at Week 8. • To evaluate the daily and weekly change in Cough Severity Visual Analogue Scale (VAS) after treatment with orvepitant to Week 4 and up to Follow-up at Week 8. • To assess the safety and tolerability of orvepitant for 4 weeks. ;Primary end point(s): The primary endpoint will be the change in objective daytime cough frequency at Week 4 compared to Baseline.;Timepoint(s) of evaluation of this end point: This endpoint will be calculated from the baseline cough frequency and the cough frequency on the final day of 4 weeks treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in objective daytime cough frequency at Weeks 1 and 8 compared to Baseline • Change in objective daytime cough frequency at Week 8 compared to Week 4 • Change in objective night-time cough frequency at Weeks 1, 4 and 8 compared to Baseline • Change in objective night-time cough frequency at Week 8 compared to Week 4 • Change in the CQLQ score at Weeks 1, 4 and 8 compared to Baseline • Change in the CQLQ score at Week 8 compared to Week 4 • Global Rating of Change for Cough Frequency and Severity Scale at Weeks 1, 4 and 8 • Cough Severity VAS at Baseline (calculated as the average of the readings recorded between the Screening and Baseline visits) and at each day and week (based on the average of the readings recorded in each week) ;Timepoint(s) of evaluation of this end point: As described above. | — |
Countries
United Kingdom
Contacts
Public ContactHead of Cough Research
University of Manchester
Outcome results
None listed