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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01656668
Recruitment Status : Completed
First Posted : August 3, 2012
Last Update Posted : August 2, 2013
Information provided by (Responsible Party):
Respicopea Limited

Tracking Information
First Submitted Date  ICMJE July 27, 2012
First Posted Date  ICMJE August 3, 2012
Last Update Posted Date August 2, 2013
Study Start Date  ICMJE July 2012
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 2, 2012)
Leicester Cough Questionnaire (LCQ) [ Time Frame: Day 14 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01656668 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 2, 2012)
  • Adapted 7-day Leicester Cough Questionnaire (LCQ) [ Time Frame: Day 7 ]
    Adapted 7-day LCQ to measure quality of life over the previous 7 days.
  • Leicester Cough Questionnaire (LCQ) [ Time Frame: Day 28 ]
    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 ]
    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 ]
    Subgroup of approximately 100 subjects will be challenged with capsaicin at Day 0 and Day 14.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 2, 2012)
Pulmonary function tests [ Time Frame: From screening to day 28 ]
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.
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Study of the Safety and Effectiveness of BC1036 Capsules to Treat Frequent Long-Term Cough
Official Title  ICMJE A Multicentre, Double-Blind, Placebo-Controlled, Adaptive Pivotal Study of the Efficacy and Safety of Oral BC1036 in the Management of Cough
Brief Summary The purpose of this study is to investigate the effect of BC1036 (theobromine) on cough-related quality of life and cough severity following 2 weeks' treatment.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cough
Intervention  ICMJE Drug: BC1036
Other Names:
  • Theobromine
  • CAS number 83-67-0
  • EV Substance code SUB15511MIG
Study Arms  ICMJE
  • Experimental: BC1036
    BC1036 300 mg capsule capsule by mouth, twice daily, for 14 days.
    Intervention: Drug: BC1036
  • Placebo Comparator: Sugar Pill
    Sugar placebo capsule by mouth, twice daily, for 14 days.
Publications * Morice AH, McGarvey L, Pavord ID, Higgins B, Chung KF, Birring SS. Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial. J Thorac Dis. 2017 Jul;9(7):1864-1872. doi: 10.21037/jtd.2017.06.18.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: August 2, 2012)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female aged 18 to 75 years.
  • Confirmed diagnosis of a persistent cough.
  • Leicester Cough Questionnaire score of ≤ 17 at baseline.
  • FEV ≥ 70% of predicted normal, at screening. See protocol Appendix 4 for formula for calculating predicted values.
  • Willing to use effective contraception for the duration of the study. Female subjects who are neither surgically sterilized nor post-menopausal (defined as no menses for one year or an FSH value > 40 mIU/L) will be required to use two methods throughout the study and for 30 days after. Besides abstinence the following contraceptive methods are acceptable: hormonal (e.g. oral, injection, transdermal patch, implant, cervical ring), barrier (e.g. condom or diaphragm with spermicidal agent) or intrauterine device. If hormonal contraceptives are used they must be used from 6 weeks before the first administration of test product. Male subjects must agree to use condoms for the duration of the study and for 30 days after.
  • Willing and able to give informed consent and of complying with the trial assessments and any other trial procedures.

Exclusion Criteria:

  • Pregnant or lactating females.
  • Major surgery within the 30 days preceding the screening visit.
  • Any serious infections within the 30 days prior to the screening visit.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes, renal or hepatic disease or psychiatric illness/social situations that would limit compliance with study requirements.
  • Known hepatitis B or C or human immunodeficiency virus (HIV) or syphilis seropositivity.
  • A history of serious adverse allergic reaction to any medication.
  • Treatment with another investigational medicinal product within the 30 days prior to enrollment.
  • Treatment with:

    • Systemic oral steroids within 7 days prior to randomisation at Visit 2.
    • Theophylline and theophylline-like agents within 7 days prior to randomisation.
    • Opiates or opioids e.g. codeine, dextromethorphan, within 7 days prior to randomisation.
    • ACE inhibitors within one month prior to the screening visit.
  • Depot injection of corticosteroids within 6 weeks of the screening visit.
  • History suggestive of febrile illness within the last 7 days prior to the screening visit.
  • Subjects with significant sputum production (defined as more than 5 ml (~one teaspoon)/day on any three days in the screening period).
  • Current smokers or past smokers who have a smoking history of > 20 pack years or stopped smoking ≤ 12 months prior to screening.
  • Any pulmonary co-morbidity such as COPD, recurrent lower respiratory tract infections (≥ 2 in the 12 months prior to screening) and bronchiectasis where cough suppression may lead to sputum retention and infection.
  • Any pulmonary abnormality on chest X-ray or CT scan performed in the twelve months prior to enrolment indicative of COPD, bronchiectasis etc.
  • Subjects diagnosed with asthma who have suffered an exacerbation requiring hospitalisation within 4 weeks prior to screening.
  • A history of cancer within the previous five years (excluding carcinoma in situ or nonmelanoma skin cancer treated by surgical excision).
  • Uncontrolled hypertension (resting systolic BP > 170mmHg or resting diastolic BP > 95 mm Hg).
  • A corrected QT interval of > 470ms for female subjects or of > 450ms for male subjects, calculated using the QTcF correction formula, or second degree or higher heart block on an ECG recording, at screening.
  • Subjects known to have a sensitivity to methylxanthines and related compounds, or known to have exhibited an allergic response or sensitivity to cocoa-based products.
  • History or presence of alcohol or substance abuse.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01656668
Other Study ID Numbers  ICMJE BC1036-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Respicopea Limited
Study Sponsor  ICMJE Respicopea Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alyn Morice, BA(Hons) MB.B.Chir MA FRCP Castle Hill Hospital
Principal Investigator: Fan Chung, MB, BS, MD, FRCP, DSc (PI) Royal Brompton & Harefield NHS Foundation Trust
Principal Investigator: Warwick Coulson, BSc, MBBS, DipRCOG, MRCGP Albany House Medical Centre
Principal Investigator: Alun George, MA MBBS, DRCOG, DCH, MRCGP Staploe Medical Centre
Principal Investigator: Bernard Higgins, MB ChB, MRCP, MD Freeman Health System
Principal Investigator: Alan Jackson, MB, BS Sheepcot Medical Centre
Principal Investigator: Philip Marazzi, MB, BS The Medical Centre
Principal Investigator: Ian Pavord, MB BS, MRCP, FRCP, DM Glenfield Hospital
Principal Investigator: Surinder Birring, BSc,MBChB(Hons),MRCP,MD(PI) King's College Hospital NHS Trust
Principal Investigator: Lorcan McGarvey, MBBCh,BAOHons,MRCP,MD,CCST(PI) The Queen's University of Belfast
Principal Investigator: Richard Oliver, MB ChB, MRCGP Ecclesfield Group Practice
Principal Investigator: Chris Strang, MB BS, D. Obst, RCOG M Mortimer Surgery
Principal Investigator: Damien McNally, MB,BCh,BAO,DRCOG,DMH,MRCGP Ormeau Road Health Centre
PRS Account Respicopea Limited
Verification Date August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP