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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Respicopea Limited
ClinicalTrials.gov Identifier:
NCT01656668
First received: July 27, 2012
Last updated: August 1, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Cough
Drug: BC1036
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicentre, Double-Blind, Placebo-Controlled, Adaptive Pivotal Study of the Efficacy and Safety of Oral BC1036 in the Management of Cough

Resource links provided by NLM:


Further study details as provided by Respicopea Limited:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 288
Study Start Date: July 2012
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BC1036
BC1036 300 mg capsule capsule by mouth, twice daily, for 14 days.
Drug: BC1036
Other Names:
  • Theobromine
  • CAS number 83-67-0
  • EV Substance code SUB15511MIG
Placebo Comparator: Sugar Pill
Sugar placebo capsule by mouth, twice daily, for 14 days.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01656668

Locations
United Kingdom
Ormeau Road Health Centre
Belfast, United Kingdom, BT7 2EB
The Queen's University of Belfast
Belfast, United Kingdom
Castle Hill Hospital
Cottingham, United Kingdom, HU16 5JQ
The Medical Centre
East Horsely, United Kingdom, KT24 6QT
Sheepcot Medical Centre
Garston, Watford, United Kingdom, WD25 0EA
Glenfield Hospital
Leicester, United Kingdom, LE3 9QP
King's College Hospital
London, United Kingdom, SE5 9RS
Royal Brompton Hospital
London, United Kingdom, SW3 6LY
Mortimer Surgery
Mortimer, United Kingdom, RG7 3SQ
Freeman Hospital
Newcastle upon Tyne, United Kingdom, NE7 7DN
Ecclesfield Group Practice
Sheffield, United Kingdom, S35 9XQ
Staploe Medical Centre
Soham, Ely, United Kingdom, CB7 5JD
Albany House Medical Centre
Wellingborough, Northampton, United Kingdom, NN8 4RW
Sponsors and Collaborators
Respicopea Limited
Investigators
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 Hospital
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 Hospital
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
  More Information

No publications provided

Responsible Party: Respicopea Limited
ClinicalTrials.gov Identifier: NCT01656668     History of Changes
Other Study ID Numbers: BC1036-001
Study First Received: July 27, 2012
Last Updated: August 1, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Respicopea Limited:
Chronic
Acute
Persistent
Longterm
Cough

Additional relevant MeSH terms:
Cough
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms
Signs and Symptoms, Respiratory

ClinicalTrials.gov processed this record on October 22, 2014