A clinical study to determine whether the medical product XEN-D0501 reduces the frequency of coughing in patients with chronic lung disease (chronic obstructive pulmonary disease).

Phase 1

• Conditions: MedDRA version: 17.0Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855; Chronic Obstructive Pulmonary Disease.; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2013-004041-17-GB
• Lead Sponsor: Xention Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-11-07
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Male and female patients aged 40 years or over with COPD, defined as:
• Smoking history of >10 pack-years,
• A post-bronchodilator forced expiratory volume in 1 second (FEV1) <80% of the predicted normal value and a ratio between FEV1 and forced vital capacity (FVC) <0.7 after 4 puffs (4 x 100 µg) of salbutamol (via pressurized metered-dose inhaler [pMDI]).
2. Day time cough frequency >1.5 coughs/hour (from 24-hour cough monitor at Visit 3),
3. For patients recruited to the Capsaicin Challenge Cohort only:
- A pre-bronchodilator FEV1 of at least 1.0 L at Visit 1
- Emax from capsaicin challenge >10 coughs (from challenge cough monitor at Visit 3)
4. Women must be of non-child bearing potential.
• Non-child bearing potential is defined as amenorrheic for at least 1 year AND, if aged under 60 years, have serum follicle stimulating hormone [FSH] level of at least 30 IU/L) or have undergone a hysterectomy or bilateral oophorectomy (tubal ligation is not acceptable). Women who are taking hormone replacement therapy (HRT) do not have to have FSH assessments, but the amenorrhea (before starting HRT) must have been naturally (spontaneously) occurring and have been accompanied by an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms).
5. If female partners of male patients are of childbearing potential, the patient must be willing to use contraception (e.g. condoms plus spermicide) AND their female partner must also be using contraception (e.g. hormonal or intra-uterine device).
This double contraception must be used from the first dose of study drug until at least 90 days after the last dose of study drug.
6. Written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 17
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1. Body Mass Index (BMI) >40 kg/m2,
2. Current smokers or patients with urine cotinine greater or equal to 500 ng/mL,
3. Ex-smoker of <6 months,
4. Upper respiratory tract infection within the last 6 weeks prior to randomisation (Visit 4),
5. COPD exacerbation requiring treatment within 6 weeks prior to randomisation (Visit 4),
6. Evidence of active microbial respiratory infection defined as the presence of significant pathogenic bacteria on sputum culture (assessed by colony forming units) at Visit 1,
7. Feverish illness within the last 1 week prior to randomisation (Visit 4),
8. Concomitant medications which may influence cough e.g. opioids, gabapentin, pregabalin, amitriptyline, ACE inhibitors, and those drugs listed in section 9.8.3
9. Use of systemic corticosteroids within 3 months of Visit 1,
10. Patient with concomitant conditions which may influence the cough reflex or the patient’s ability to participate in the study e.g. diabetes, cerebrovascular disease, Parkinson’s disease. N.B. Patients with type 2 diabetes may be included if, in the opinion of the investigator, they are well controlled and have no history suggestive of autonomic neuropathy;
11. History of drug or alcohol dependency or abuse within approximately the last year prior to Visit 1,
12. Regular alcohol consumption; >21 units/week for males, or >14 units/week for females, during the study (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
13. Any known allergy to the study drugs,
14. Pregnant and/or lactating women,
15. History or evidence of urinary retention, bladder outlet obstruction or benign prostatic hypertrophy,
16. Any clinically significant abnormalities in haematology or clinical biochemistry tests prior to randomisation (Visit 4).
17. Serum alanine transaminase (ALT), aspartate transaminase (AST) or gamma-glutamyl transpeptidase (GGT) greater than twice the upper limit of normal (ULN) at Visits 1 or 2,
18. Total serum bilirubin >1.5x ULN at Visits 1 or 2,
19. History of any kind of cancer within the last 5 years unless non-invasive, in remission and approved in writing by Sponsor,
20. COPD with respiratory failure that requires long term oxygen therapy,
21. Evidence of any other clinically significant disease or condition which in the opinion of the investigator would preclude the patient’s participation in this study,
22. QTcF value at Visit 1 (mean) or Visit 2 of >450 msec (males) or >470 msec (females)
23. Patients with uncontrolled hypertension, systolic blood pressure >160 mmHg or diastolic blood pressure >90 mmHg at Visit 1 (mean) or Visit 2.
24. Received investigational or marketed products as part of any other clinical study within 30 days (or 5 half-lives whichever is longer) prior to Visit 1,
25. Patient is unable or unwilling to co-operate with the study procedures.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effectiveness of XEN-D0501 over placebo in reducing objective daytime cough frequency.;Primary end point(s): Change from baseline after 14-days treatment in objective daytime cough frequency on XEN-D0501 compared to placebo.;Timepoint(s) of evaluation of this end point: 14 days;Secondary Objective: • To evaluate the effectiveness of XEN-D0501 over placebo in reducing:<br>o capsaicin cough responses,<br>o objective 24-hour cough frequency,<br>o hourly change in cough frequency,<br>o cough severity (via visual analogue scale (VAS)).<br>o urge to cough (via VAS),<br>o global rating of change scale,<br>o Clinical COPD Questionnaire (CCQ),<br>o Leicester Cough Questionnaire (LCQ),<br>o St George's Respiratory Questionnaire (SGRQ-C)

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: 14 days;Secondary end point(s): Change from baseline after at the end of each treatment period for the following parameters:<br>• Capsaicin cough response (Emax) - Capsaicin Challenge Cohort only<br>• Objective 24-hour cough frequency<br>• Clinical COPD Questionnaire<br>• SGRQ-C<br>• Leicester Cough Questionnaire<br>The assessments at the end of each treatment period for:<br>• Hourly change in cough frequency<br>• Global rating of change scale<br>Change from baseline over each treatment period for the following parameters:<br>• Cough severity (VAS)<br>• Urge to cough (VAS)