Chronic cough MedDRA version: 17.1 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000004855
Conditions
Interventions
Product Name: Lesogaberan (AZD 3355)
Product Code: AZD 3355
Pharmaceutical Form: Capsule
INN or Proposed INN: Lesogaberan
CAS Number: 344413-67-8
Other descriptive name: AZD3355
Concentration unit:
Sponsors
University Hospital South Manchester NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed, written and dated informed consent, prior to any study specific procedures. 2. Aged above 18 years old. 3. Agreement to comply with contraception restrictions as outlined in section 8.3.4 4. BMI of 19-35 kg/m2 (inclusive) 5. Normal spirometry. 6. Chronic dry cough of at least 8 weeks duration. 7. Normal chest X-ray. 8. Patients with cough related to nasal disease, reflux and asthma will be included. These conditions will be investigated but they will still be included. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. History of cardiac disease, clinically significant orthostatic reactions or syncope, renal disease and hepatic disease . 2. Prolonged QTcF >450ms or family history of long QT syndrome at baseline (any prolongation of QTcF during the study will be classed as an AE unless >500 or deemed clinically significant by the research physician) 3. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG at enrolment that may interfere with the interpretation of the QTc interval changes. This includes subjects with any of the following: • Clinically significant PR interval prolongation • Intermittent second or third degree AV block • Incomplete, full or intermittent bundle branch block (QRS20 pack year history, and <6 months abstinence. 10. History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class as Lesogaberan. 11. History of drug addiction and/or alcohol abuse or other circumstances which in the investigators judgement may compromise the subject’s ability to comply with the study requirements. 12. Pregnancy or breastfeeding. 13. Treatment with ACE inhibitors will be excluded. Patients taking centrally acting medications e.g. opiates, amitriptyline, gabapentin, pregabalin for the treatment of cough, will be excluded unless they are willing to stop these treatments. Patients can be included if they are willing to stop opiates for 1 week prior to baseline visit through to follow-up visit. Pregabalin, gabapentin, amitriptyline and ACEi will need to be stopped for 4 weeks prior to baseline visit and through to follow-up visit. 14. Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within 3 months of anticipated first administration of therapy in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of 2 weeks of Lesogaberan treatment compared with 2 weeks of placebo treatment on 24 hour cough frequency. Lay description: To test what effect a drug called Lesogaberan has on how much a person coughs in a 24 hour period compared to if that person was taking a dummy drug with no active ingredients (called placebo).;Secondary Objective: There are 6 secondary objectives that need to be addressed: 1) The effect of 2 weeks treatment with Lesogaberan on the cough response to capsaicin (chilli pepper). Do patients cough less times and are they less sensitive to the capsaicin? 2) What is the effect of first dose of Lesogaberan on the cough response to capsaicin? 3) The effect of Lesogaberan on the severity of cough and quality of life 4) The effect of Leosgaberan on gastroesophageal reflux disease symptoms? 5) The safety and tolerability of Lesogaberan in patients with chronic cough 6) 24hr cough frequency for SAP positive vs. SAP negative patients after 2 weeks treatment;Primary end point(s): 24 hour objective cough frequency following 2 week treatment with Lesogaberan compared with placebo.;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 2 weeks treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine the effects of Lesogaberan compared with placebo on: 24hr cough frequency following one day’s treatment. Cough reflex sensitivity to capsaicin after 2 weeks treatment, Cough reflex sensitivity to capsaicin (on first treatment day) following one day’s treatment 24hr cough frequency for (symptom associated probability) SAP positive vs. SAP negative patients after 2 weeks treatment 24hr cough frequency for SAP positive vs. SAP negative patients on first treatment day, Cough severity VAS and cough specific quality of life. Measure of GORD symptoms ;Timepoint(s) of evaluation of this end point: As described above. | — |
Countries
United Kingdom
Contacts
Public ContactJaclyn Smith
University of Manchester
Outcome results
None listed