CoughPhase 3NCT01656668
Study of the Safety and Effectiveness of BC1036 Capsules to Treat Frequent Long-Term Cough
A Phase 3 study testing BC1036 in people with Cough, run by Respicopea Limited at 13 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cough
- What is being tested?
- BC1036
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 288 participants
- Where
- 13 sitesUnited Kingdom
- Study dates
- Jul 2012to Aug 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 24Show fewer
- 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.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United Kingdom13 sites
Ormeau Road Health Centre
Belfast, BT7 2EB
The Queen's University of Belfast
Belfast
Castle Hill Hospital
Cottingham, HU16 5JQ
The Medical Centre
East Horsely, KT24 6QT
Sheepcot Medical Centre
Garston, Watford, WD25 0EA
Glenfield Hospital
Leicester, LE3 9QP
King's College Hospital
London, SE5 9RS
Royal Brompton Hospital
London, SW3 6LY
Mortimer Surgery
Mortimer, RG7 3SQ
Freeman Hospital
Newcastle upon Tyne, NE7 7DN
Ecclesfield Group Practice
Sheffield, S35 9XQ
Staploe Medical Centre
Soham, Ely, CB7 5JD
Albany House Medical Centre
Wellingborough, Northampton, NN8 4RW
About this study
Official title: A Multicentre, Double-Blind, Placebo-Controlled, Adaptive Pivotal Study of the Efficacy and Safety of Oral BC1036 in the Management of Cough
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.
Read the 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.
- Conditions
- Cough
- Being tested
- BC1036
- Keywords
- Chronic, Acute, Persistent, Longterm, Cough
- Medical subject headings
- Cough, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BC1036Drug
Also called Theobromine, CAS number 83-67-0, EV Substance code SUB15511MIG
| Study group | Role | What they receive |
|---|---|---|
| BC1036 | Experimental | BC1036 300 mg capsule capsule by mouth, twice daily, for 14 days. Receives: Drug: BC1036 |
| Sugar Pill | Placebo comparator | Sugar placebo capsule by mouth, twice daily, for 14 days. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Leicester Cough Questionnaire (LCQ)
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.
Measured: Day 14
Secondary outcomes (4)
Adapted 7-day Leicester Cough Questionnaire (LCQ)
Adapted 7-day LCQ to measure quality of life over the previous 7 days.
Measured: Day 7
Leicester Cough Questionnaire (LCQ)
LCQ at Day 28 will measure quality of life over the previous 14 days.
Measured: Day 28
Cough visual analogue scale (VAS)
VAS scores on a 100 mm scale fixed at both ends by 'no cough' and 'worst cough ever'. Assessment made at every visit.
Measured: From screening to Day 28
Airway sensitivity using capsaicin challenge
Subgroup of approximately 100 subjects will be challenged with capsaicin at Day 0 and Day 14.
Measured: Day 0 and Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2012 (estimated)
- Study startJul 2012
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CoughStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 288 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Respicopea Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alyn Morice, BA(Hons) MB.B.Chir MA FRCP, Principal investigator, Castle Hill HospitalFan Chung, MB, BS, MD, FRCP, DSc (PI), Principal investigator, Royal Brompton & Harefield NHS Foundation TrustWarwick Coulson, BSc, MBBS, DipRCOG, MRCGP, Principal investigator, Albany House Medical CentreAlun George, MA MBBS, DRCOG, DCH, MRCGP, Principal investigator, Staploe Medical CentreBernard Higgins, MB ChB, MRCP, MD, Principal investigator, Freeman Health SystemAlan Jackson, MB, BS, Principal investigator, Sheepcot Medical CentrePhilip Marazzi, MB, BS, Principal investigator, The Medical CentreIan Pavord, MB BS, MRCP, FRCP, DM, Principal investigator, Glenfield Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01656668
- Sponsor's protocol ID
- BC1036-001
- Status last verified
- Aug 2013
- First submitted
- 27 Jul 2012
- Last updated
- 2 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 28839984
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Double-Blind, Placebo-Controlled, Adaptive Pivotal Study of the Efficacy and Safety of Oral BC1036 in the Management of Cough
- ClinicalTrials.gov ID
- NCT01656668
- Acronym / sponsor ID
- BC1036-001
- Conditions
- Cough
- Keywords
- Chronic, Acute, Persistent, Longterm, Cough
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 288 participants (estimated)
- Lead sponsor
- Respicopea LimitedIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 3 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BC1036 | Experimental | Drug: BC1036BC1036 300 mg capsule capsule by mouth, twice daily, for 14 days. |
| Sugar Pill | Placebo comparator | –Sugar placebo capsule by mouth, twice daily, for 14 days. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BC1036Also: Theobromine, CAS number 83-67-0, EV Substance code SUB15511MIG | Drug | BC1036 |
Primary outcome
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.
4 secondary outcomes
Adapted 7-day Leicester Cough Questionnaire (LCQ)
Time frame: Day 7
Leicester Cough Questionnaire (LCQ)
Time frame: Day 28
Cough visual analogue scale (VAS)
Time frame: From screening to Day 28
Airway sensitivity using capsaicin challenge
Time frame: Day 0 and Day 14
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2013.
- Derived from this study: PubMed 28839984Morice 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.
Related trials for Cough
RecruitingPhase 2
The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)
Refractory Chronic Cough
RecruitingObservational study
Physical Impairments in Premature Ventricular Complex
Premature Ventricular Complexes
RecruitingObservational study
Office-Based Superior Laryngeal Nerve Block for Treatment of Neurogenic Cough
Cough
Not yet recruiting
High-Flow Nasal Oxygen-Assisted Deep Extubation Versus Awake Extubation in Morbidly Obese Patients
Deep Tracheal Extubation
Recruiting
Feasibility of Cough Skill Training in Individuals With Head and Neck Cancer
Head and Neck Cancers
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alyn Morice, BA(Hons) MB.B.Chir MA FRCP principal investigator
Castle Hill Hospital
Fan Chung, MB, BS, MD, FRCP, DSc (PI) principal investigator
Royal Brompton & Harefield NHS Foundation Trust
Warwick Coulson, BSc, MBBS, DipRCOG, MRCGP principal investigator
Albany House Medical Centre
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BC1036 in people with Cough, run by Respicopea Limited at 13 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Leicester Cough Questionnaire (LCQ) (time frame: Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01656668, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2013.