Study of the Safety and Effectiveness of BC1036 Capsules to Treat Frequent Long-Term Cough

• Leicester Cough Questionnaire (LCQ) [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
  Cough-related quality of life assessed using the Leicester Cough Questionnaire (LCQ). The baseline-adjusted total LCQ score at Day 14 will be used as the primary endpoint.
  
  

• Adapted 7-day Leicester Cough Questionnaire (LCQ) [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
  Adapted 7-day LCQ to measure quality of life over the previous 7 days.
  
  
• Leicester Cough Questionnaire (LCQ) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  LCQ at Day 28 will measure quality of life over the previous 14 days.
  
  
• Cough visual analogue scale (VAS) [ Time Frame: From screening to Day 28 ] [ Designated as safety issue: No ]
  VAS scores on a 100 mm scale fixed at both ends by 'no cough' and 'worst cough ever'. Assessment made at every visit.
  
  
• Airway sensitivity using capsaicin challenge [ Time Frame: Day 0 and Day 14 ] [ Designated as safety issue: No ]
  Subgroup of approximately 100 subjects will be challenged with capsaicin at Day 0 and Day 14.
  
  

• Pulmonary function tests [ Time Frame: From screening to day 28 ] [ Designated as safety issue: No ]
  Pulmonary function will be measured at all visits using a calibrated spirometer. This includes Forced Expiratory Volume (FEV), Forced Vital Capacity (FVC) and peak flow.
  
  

Cough is a common and disabling symptom. At any one time 20% of the population have a troublesome cough and sufferers consume 75 million doses of over-the-counter anti-tussive (anti-cough) medication annually. Chronic cough can be the presenting symptom of almost all respiratory conditions; it can also occur in the absence of overt lung pathology. The only study to grade cough severity found 7% of a general population had cough sufficient to interfere with activities of daily living on at least a weekly basis in the UK. Cross sectional studies have consistently shown that chronic cough is particularly prevalent in middle aged females.

The investigational medicinal product BC1036 (theobromine) is being developed as a non-codeine, non-narcotic treatment for persistent cough. Theobromine is a well characterised molecule with a long history of safe use both as a medicine and as a food product. As a member of the xanthine family, it bears structural and pharmacological similarity to caffeine and theophylline, both of which have long been approved for medicinal use.

This is a placebo-controlled, double-blind, parallel group study of BC1036 in subjects with persistent cough (chronic or sub-acute), treatment resistant after a routine clinical assessment as outlined in the BTS Recommendations for the Management of Cough in Adults and despite adequate treatment of any associated potential aggravating factors or without the continuance of any obvious precipitating factors. The objective is to investigate the effect of BC1036 on cough-related quality of life and cough severity following 2 weeks' treatment. It is planned to recruit 288 evaluable subjects from cough clinics, secondary and primary care centres in the UK. Subjects will receive either BC1036 or placebo over a period of 14 days.

Eligible subjects will be required to attend the clinic on five occasions: screening, baseline, days 7, 14, and a follow up visit at day 28. At every visit the subjects will complete the Leicester Cough Questionnaire (LCQ), and a cough Visual Analogue Score (VAS). Spirometry will be performed for measurement of lung function. Blood samples will be drawn for safety clinical laboratory parameters and physical examinations and ECG will be performed. Subjects should be seen for all visits on the designated day ± 1 day, except Day 28 ± 2 days.