E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066656 |
E.1.2 | Term | Chronic cough |
E.1.2 | System Organ Class | 100000004855 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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 (QRS<11ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy) 4. Abnormal T wave morphology, particularly in the protocol define primary lead 5. Any clinically significant illness, medical or surgical procedure or trauma within the 4 weeks preceding the first administration of study medication including upper respiratory tract infections. 6. Any clinically significant abnormalities in clinical chemistry, haematology results as judged by the investigator. 7. Abnormal screening clinical pathology values or other clinically significant, unexplained biochemical abnormality according to the investigator; in particular, liver function tests (LFTs) should be within normal limits at screening. 8. Systolic blood pressure below 110 mm Hg at screening. 9. Current smoker or ex-smoker with >20 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
24 hour objective cough frequency following 2 week treatment with Lesogaberan compared with placebo. |
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E.5.1.1 | 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. |
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E.5.2 | 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 1 |