Pulmonary Disease, Chronic ObstructivePhase 1NCT00549120
Optimising the Propranolol Block Model
A Phase 1 study testing Propranolol, Salbutamol and Ipratropium in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
Optimising the propranolol block model Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Propranolol, Salbutamol and Ipratropium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Aug 2007to 26 Oct 2007
- Phase
- Phase 1
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adult male or female aged between 18 and 50 years.
- Body mass index within the range 19-29.9 kilograms/metre2
- Forced Expiratory Volume in 1 second (FEV1) >80% predicted and a FEV1/ Forced Vital Capacity (FVC) ratio > 0.7
- The subject has an increase in sGAW of >% over pre-dose baseline within 2 h of administration of 400 ug salbutamol by MDI inhaler at screening or in the 3 months before screening.
- Subject has an increase in sGaw of 25% over pre-dose baseline within 2 h following 40 ug ipratropium bromide at screening or in the 3 months before screening
- Subjects are current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of < 10 pack years.
Who cannot join
- A past or present disease, which as judged by the Investigator and medical monitor may affect the outcome of the study or the safety of the subject
- History of respiratory disease
- Significant abnormal 12 lead ECG, QTc(B) and QTc(F) value at screening >450msec on an individual ECG or a PR interval outside the range 120-210 msec
- Supine mean heart rate outside the range 45-90 beats per minute (bpm) at screening
- Subject has donated a unit of blood within the 56 days or intends to donate within 56 days after completing the study
- Subject is currently taking regular (or course of) medication whether prescribed or not (with the exception of contraceptives, including vitamins and herbal remedies such as St John's Wort)
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- Subject has participated in a clinical study with a New Chemical Entity (NCE) within the past 1 month
- Infected with the Hepatitis B, Hepatitis C, or HIV virus
- Subject has a history of drug or other allergy, which, in the opinion of the Investigator, contraindicates their participation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Study to Optimise the Propranolol Block Model for Assessment of the Pharmacological Activity of Bronchodilators in Healthy Volunteers.
Optimising the propranolol block model
Read the detailed description
The bronchodilatory effects of inhaled beta2 agonists and anti-muscarinic drugs are the mainstay of symptomatic treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD). A new approach is to combine both pharmacological approaches in a single molecule - ie a dual pharmacophore. It will be necessary to explore the relative contribution of the beta2 agonist versus anti-muscarinic bronchodilator properties of such a molecule. One way to do that is to block one of the components. Inhibition of beta2 agonist-mediated bronchodilatation by the non-selective beta-blocker propranolol is an established experimental method. Therefore this method may be useful in exploring the pharmacology of a dual pharmacophore.
Published studies have generally looked at the effect of a single dose of propranolol on a beta2 agonist over a relatively short period of time (a few hours). There is a desire to develop long acting bronchodilators that require once daily dosing only. Thus any dual pharmacophore developed is likely to have 24 hour duration of action after a single dose. Therefore to use this method of beta blockade to inhibit beta2 agonist mediated bronchodilation, it is necessary to confirm a dosing regimen of propranolol that has acceptable tolerability and is effective in blocking the effects of a beta2 agonist over 24 hours. That is the main purpose of this study.
It is also important to confirm that the bronchodilator effect of an antimuscarinic is unaffected by beta blockade. In addition, it is of interest to examine the bronchodilator effect of a combination of an antimuscarinic and beta2 agonist in healthy volunteers and the effect of propranolol on the combination.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Propranolol, Salbutamol, Ipratropium, Placebo
- Keywords
- Healthy Subjects, muscarinic receptor antagonist, propranolol, beta-blocker, beta-agonist
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
40 mg tablets
SalbutamolDrug
Metered dose inhaler (600 μg)
IpratropiumDrug
Metered dose inhaler (40 μg)
PlaceboDrug
Placebo for propranolol tablets
| Study group | Role | What they receive |
|---|---|---|
| Propranolol alone | Experimental | Propranolol 80 mg (5 doses at 6 hourly intervals) Receives: Drug: Propranolol |
| Propranolol + salbutamol | Experimental | Propranolol 80 mg (5 doses at 6 hourly intervals) + salbutamol 600 μg (4 doses at 6 hourly intervals) Receives: Drug: Propranolol; Drug: Salbutamol |
| Salbutamol alone | Experimental | Salbutamol 600 μg (4 doses at 6 hourly) + placebo (5 doses at 6 hourly intervals) Receives: Drug: Salbutamol; Drug: Placebo |
| Placebo | Placebo comparator | Placebo (5 doses at 6 hourly) Receives: Drug: Placebo |
| Propranolol + ipratropium + salbutamol | Experimental | Propranolol 80 mg (2 doses at 6 hourly intervals) + ipratropium bromide 40 μg (2 doses at 6 hourly interval) + salbutamol 600 μg (1 dose) Receives: Drug: Propranolol; Drug: Salbutamol; Drug: Ipratropium |
| Placebo + ipratropium + salbutamol | Experimental | Placebo (2 doses at 6 hourly intervals) + ipratropium bromide 40 μg (2 doses at 6 hourly interval) + salbutamol 600 μg (1 dose) Receives: Drug: Salbutamol; Drug: Ipratropium; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Specific airway conductance (sGAW)
Measured: Pre-dose and up to 26 h post-dose
Secondary outcomes (2)
Tolerability: adverse events, 12 lead ECG, blood pressure and heart rate
Measured: Study duration
Propranolol pharmacokinetics
Measured: Pre-dose and up to 28 h post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2007 (estimated)
- Study start15 Aug 2007
- Primary completion26 Oct 2007
- Study completion26 Oct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00549120
- Sponsor's protocol ID
- MAB104954
- Status last verified
- Aug 2017
- First submitted
- 23 Oct 2007
- Last updated
- 4 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Optimise the Propranolol Block Model for Assessment of the Pharmacological Activity of Bronchodilators in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT00549120
- Acronym / sponsor ID
- MAB104954
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- Healthy Subjects, muscarinic receptor antagonist, propranolol, beta-blocker, beta-agonist
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 15 Aug 2007 (actual)
- Primary completion
- 26 Oct 2007 (actual)
- Study completion
- 26 Oct 2007 (actual)
- First posted
- 25 Oct 2007 (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.
Optimising the propranolol block model
Detailed description
The bronchodilatory effects of inhaled beta2 agonists and anti-muscarinic drugs are the mainstay of symptomatic treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD). A new approach is to combine both pharmacological approaches in a single molecule - ie a dual pharmacophore. It will be necessary to explore the relative contribution of the beta2 agonist versus anti-muscarinic bronchodilator properties of such a molecule. One way to do that is to block one of the components. Inhibition of beta2 agonist-mediated bronchodilatation by the non-selective beta-blocker propranolol is an established experimental method. Therefore this method may be useful in exploring the pharmacology of a dual pharmacophore.
Published studies have generally looked at the effect of a single dose of propranolol on a beta2 agonist over a relatively short period of time (a few hours). There is a desire to develop long acting bronchodilators that require once daily dosing only. Thus any dual pharmacophore developed is likely to have 24 hour duration of action after a single dose. Therefore to use this method of beta blockade to inhibit beta2 agonist mediated bronchodilation, it is necessary to confirm a dosing regimen of propranolol that has acceptable tolerability and is effective in blocking the effects of a beta2 agonist over 24 hours. That is the main purpose of this study.
It is also important to confirm that the bronchodilator effect of an antimuscarinic is unaffected by beta blockade. In addition, it is of interest to examine the bronchodilator effect of a combination of an antimuscarinic and beta2 agonist in healthy volunteers and the effect of propranolol on the combination.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Propranolol alone | Experimental | Drug: PropranololPropranolol 80 mg (5 doses at 6 hourly intervals) |
| Propranolol + salbutamol | Experimental | Drug: Propranolol, Drug: SalbutamolPropranolol 80 mg (5 doses at 6 hourly intervals) + salbutamol 600 μg (4 doses at 6 hourly intervals) |
| Salbutamol alone | Experimental | Drug: Salbutamol, Drug: PlaceboSalbutamol 600 μg (4 doses at 6 hourly) + placebo (5 doses at 6 hourly intervals) |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (5 doses at 6 hourly) |
| Propranolol + ipratropium + salbutamol | Experimental | Drug: Propranolol, Drug: Salbutamol, Drug: IpratropiumPropranolol 80 mg (2 doses at 6 hourly intervals) + ipratropium bromide 40 μg (2 doses at 6 hourly interval) + salbutamol 600 μg (1 dose) |
| Placebo + ipratropium + salbutamol | Experimental | Drug: Salbutamol, Drug: Ipratropium, Drug: PlaceboPlacebo (2 doses at 6 hourly intervals) + ipratropium bromide 40 μg (2 doses at 6 hourly interval) + salbutamol 600 μg (1 dose) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Healthy adult male or female aged between 18 and 50 years.
- Body mass index within the range 19-29.9 kilograms/metre2
- Forced Expiratory Volume in 1 second (FEV1) >80% predicted and a FEV1/ Forced Vital Capacity (FVC) ratio > 0.7
- The subject has an increase in sGAW of >% over pre-dose baseline within 2 h of administration of 400 ug salbutamol by MDI inhaler at screening or in the 3 months before screening.
- Subject has an increase in sGaw of 25% over pre-dose baseline within 2 h following 40 ug ipratropium bromide at screening or in the 3 months before screening
Key exclusion criteria (9 listed)
- A past or present disease, which as judged by the Investigator and medical monitor may affect the outcome of the study or the safety of the subject
- History of respiratory disease
- Significant abnormal 12 lead ECG, QTc(B) and QTc(F) value at screening >450msec on an individual ECG or a PR interval outside the range 120-210 msec
- Supine mean heart rate outside the range 45-90 beats per minute (bpm) at screening
- Subject has donated a unit of blood within the 56 days or intends to donate within 56 days after completing the study
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 |
|---|---|---|
| Propranolol40 mg tablets | Drug | Propranolol + ipratropium + salbutamol, Propranolol + salbutamol, Propranolol alone |
| SalbutamolMetered dose inhaler (600 μg) | Drug | Placebo + ipratropium + salbutamol, Propranolol + ipratropium + salbutamol, Propranolol + salbutamol, Salbutamol alone |
| IpratropiumMetered dose inhaler (40 μg) | Drug | Placebo + ipratropium + salbutamol, Propranolol + ipratropium + salbutamol |
| PlaceboPlacebo for propranolol tablets | Drug | Placebo, Placebo + ipratropium + salbutamol, Salbutamol alone |
Primary outcome
Specific airway conductance (sGAW)
Time frame: Pre-dose and up to 26 h post-dose
2 secondary outcomes
Tolerability: adverse events, 12 lead ECG, blood pressure and heart rate
Time frame: Study duration
Propranolol pharmacokinetics
Time frame: Pre-dose and up to 28 h post-dose
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 4 Aug 2017.
- Results for study MAB104954 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Propranolol, Salbutamol and Ipratropium in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site 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 9 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 4 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Specific airway conductance (sGAW) (time frame: Pre-dose and up to 26 h post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Aug 2017.