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Optimising the Propranolol Block Model

Primary Purpose

Pulmonary Disease, Chronic Obstructive

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Propranolol

Salbutamol

Ipratropium

Placebo

About this trial

This is an interventional basic science trial for Pulmonary Disease, Chronic Obstructive focused on measuring Healthy Subjects, muscarinic receptor antagonist, propranolol, beta-blocker, beta-agonist

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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.

Exclusion criteria:

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)
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

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Propranolol alone

Propranolol + salbutamol

Salbutamol alone

Placebo

Propranolol + ipratropium + salbutamol

Placebo + ipratropium + salbutamol

Arm Description

Propranolol 80 mg (5 doses at 6 hourly intervals)

Propranolol 80 mg (5 doses at 6 hourly intervals) + salbutamol 600 μg (4 doses at 6 hourly intervals)

Salbutamol 600 μg (4 doses at 6 hourly) + placebo (5 doses at 6 hourly intervals)

Placebo (5 doses at 6 hourly)

Propranolol 80 mg (2 doses at 6 hourly intervals) + ipratropium bromide 40 μg (2 doses at 6 hourly interval) + salbutamol 600 μg (1 dose)

Placebo (2 doses at 6 hourly intervals) + ipratropium bromide 40 μg (2 doses at 6 hourly interval) + salbutamol 600 μg (1 dose)

Outcomes

Primary Outcome Measures

Specific airway conductance (sGAW)

Secondary Outcome Measures

Tolerability: adverse events, 12 lead ECG, blood pressure and heart rate

Propranolol pharmacokinetics

Full Information

NCT ID

NCT00549120

First Posted

October 23, 2007

Last Updated

August 2, 2017

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00549120

Brief Title

Optimising the Propranolol Block Model

Official Title

A Study to Optimise the Propranolol Block Model for Assessment of the Pharmacological Activity of Bronchodilators in Healthy Volunteers.

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Completed

Study Start Date

August 15, 2007 (Actual)

Primary Completion Date

October 26, 2007 (Actual)

Study Completion Date

October 26, 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Disease, Chronic Obstructive

Keywords

Healthy Subjects, muscarinic receptor antagonist, propranolol, beta-blocker, beta-agonist

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Propranolol alone

Arm Type

Experimental

Arm Description

Propranolol 80 mg (5 doses at 6 hourly intervals)

Arm Title

Propranolol + salbutamol

Arm Type

Experimental

Arm Description

Propranolol 80 mg (5 doses at 6 hourly intervals) + salbutamol 600 μg (4 doses at 6 hourly intervals)

Arm Title

Salbutamol alone

Arm Type

Experimental

Arm Description

Salbutamol 600 μg (4 doses at 6 hourly) + placebo (5 doses at 6 hourly intervals)

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo (5 doses at 6 hourly)

Arm Title

Propranolol + ipratropium + salbutamol

Arm Type

Experimental

Arm Description

Propranolol 80 mg (2 doses at 6 hourly intervals) + ipratropium bromide 40 μg (2 doses at 6 hourly interval) + salbutamol 600 μg (1 dose)

Arm Title

Placebo + ipratropium + salbutamol

Arm Type

Experimental

Arm Description

Placebo (2 doses at 6 hourly intervals) + ipratropium bromide 40 μg (2 doses at 6 hourly interval) + salbutamol 600 μg (1 dose)

Intervention Type

Drug

Intervention Name(s)

Propranolol

Intervention Description

40 mg tablets

Intervention Type

Drug

Intervention Name(s)

Salbutamol

Intervention Description

Metered dose inhaler (600 μg)

Intervention Type

Drug

Intervention Name(s)

Ipratropium

Intervention Description

Metered dose inhaler (40 μg)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo for propranolol tablets

Primary Outcome Measure Information:

Title

Specific airway conductance (sGAW)

Time Frame

Pre-dose and up to 26 h post-dose

Secondary Outcome Measure Information:

Title

Tolerability: adverse events, 12 lead ECG, blood pressure and heart rate

Time Frame

Study duration

Title

Propranolol pharmacokinetics

Time Frame

Pre-dose and up to 28 h post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion criteria: 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) 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

London

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Links:

URL

https://www.clinicalstudydatarequest.com

Description

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Available IPD and Supporting Information:

Available IPD/Information Type

Annotated Case Report Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

MAB104954

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

MAB104954

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Informed Consent Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

MAB104954

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Study Protocol

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

MAB104954

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Dataset Specification

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

MAB104954

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Statistical Analysis Plan

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

MAB104954

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Clinical Study Report

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

MAB104954

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

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Optimising the Propranolol Block Model

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