GSK159802 In Healthy Male Subjects And Asthmatics

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00364273

Collaborator

(none)

Enrollment

Locations

Arms

10.4

Actual Duration (Months)

21.5

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

GSK159802 is a potent, inhaled, long acting selective beta-2-receptor agonist (LABA), which is being developed for once daily treatment of asthma and COPD as part of a combination product with a once daily inhaled corticosteroid and also as a standalone product for the treatment of COPD. Stimulation of the beta-2-agonist in the lung mainly relaxes bronchial smooth muscle cells which results in bronchodilation. Unwanted systemic side effects related with beta-2-agonist treatment such as tachycardia, tremor, hyperglycemia and hypokalemia are limited by local administration and also tend to show tachyphylaxis.

The LABAs that are currently available (e.g., salmeterol, formoterol) require twice-daily administration, given their duration of action. Therefore, there is significant opportunity for a once-daily inhaled medication to improve patient compliance and overall disease management by providing sustained, 24-hour bronchodilation.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: GSK159802 Drug: Placebo Drug: Salmeterol	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Primary Purpose:

Treatment

Official Title:

A Randomised, Double Blind, Placebo Controlled Study to Examine the Safety, Tolerability, Pharmacodynamics and Pharmacokinetic Profile of Single Inhaled Dry Powder Doses of GSK159802 in Healthy Male Subjects

Actual Study Start Date :

Aug 24, 2005

Actual Primary Completion Date :

Jul 6, 2006

Actual Study Completion Date :

Jul 6, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subjects receiving treatment sequence 1 : Cohort 1 Eligible subjects will receive placebo, GSK159802 300 micrograms, GSK159802 600 micrograms, GSK159802 900 micrograms and GSK159802 1200 micrograms.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 2 : Cohort 1 Eligible subjects will receive GSK159802 150 micrograms, placebo, GSK159802 600 micrograms, GSK159802 900 micrograms and GSK159802 1200 micrograms.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 3 : Cohort 1 Eligible subjects will receive GSK159802 150 micrograms, GSK159802 300 micrograms, placebo, GSK159802 900 micrograms and GSK159802 1200 micrograms.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 4 : Cohort 1 Eligible subjects will receive GSK159802 150 micrograms, GSK159802 300 micrograms, GSK159802 600 micrograms, placebo and GSK159802 1200 micrograms.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 5 : Cohort 1 Eligible subjects will receive GSK159802 150 micrograms, GSK159802 300 micrograms, GSK159802 600 micrograms, GSK159802 900 micrograms and placebo.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 1 : Cohort 2 Eligible subjects will receive placebo, salmeterol, GSK159802 low dose (LD) and GSK159802 maximum tolerated dose (MTD).	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 2 : Cohort 2 Eligible subjects will receive salmeterol, GSK159802 MTD, placebo and GSK159802 LD.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 3 : Cohort 2 Eligible subjects will receive GSK159802 LD, placebo, GSK159802 MTD and salmeterol.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 4 : Cohort 2 Eligible subjects will receive GSK159802 MTD, GSK159802 LD, salmeterol and placebo.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 1 : Cohort 3 Eligible subjects will receive placebo, salmeterol, GSK159802 300 micrograms and GSK159802 1200 micrograms.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 2 : Cohort 3 Eligible subjects will receive salmeterol, GSK159802 1200 micrograms, placebo and GSK159802 300 micrograms.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 3 : Cohort 3 Eligible subjects will receive GSK159802 300 micrograms, placebo, GSK159802 1200 micrograms and salmeterol.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 4 : Cohort 3 Eligible subjects will receive GSK159802 1200 micrograms, GSK159802 300 micrograms, salmeterol and placebo.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.
Experimental: Subjects receiving treatment sequence 5 : Cohort 3 Eligible subjects will receive GSK159802 1200 micrograms, salmeterol, GSK159802 300 micrograms and placebo.	Drug: GSK159802 GSK159802 will be available with dosing strengths of 75 microgram per blister and 300 microgram per blister administered using DISKUS inhaler. Drug: Placebo Subjects will receive placebo administered using DISKUS inhaler. Drug: Salmeterol Salmeterol will be available with dosing strength of 50 micrograms per blister administered using DISKUS inhaler.

Outcome Measures

Primary Outcome Measures

Safety & tolerability of single inhaled doses of GSK159802. [Up to 71 days]

Secondary Outcome Measures

sGaw (Cohorts 1 and 2 only) and FEV1 Systemic & urine pharmacokinetics of GSK159802 and SKF-91300 Heart rate, potassium, glucose, 12-lead ECG & blood pressure [Up to 71 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion criteria:

Body mass index within the range 18.5-29.9 (kg/m2)
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.

Additional criteria for Cohorts 2 and 3 only (Asthmatic Patients):

Subjects with a documented history of mild to moderate asthma, with the exclusion of other significant pulmonary disease
Subjects with clinically stable asthma within the 4 weeks preceding the screening visit and with a screening pre-bronchodilator FEV1 greater than 60% and less than 90% predicted.

During the screening visit, subjects must demonstrate the presence of reversible airway disease, defined as an increase in FEV1 of > or equal to 12.0% over baseline and an absolute change of > or equal to 300 mL within 30 minutes following 400 mcg salbutamol.

Exclusion criteria:

Any clinically relevant abnormality
Subjects who have a screening haemoglobin values < 11 g/dL
The subject has participated in a clinical study with a New Chemical Entity (NCE) within the past 112 days or a clinical study with any other drug during the previous 84 days
Subjects with known hypersensitivity to salmeterol or salbutamol or any ingredients in their preparations.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Manchester	Lancashire	United Kingdom	M23 9LT
2	GSK Investigational Site	London		United Kingdom

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00364273

Other Study ID Numbers:

B2F104300

First Posted:

Aug 15, 2006

Last Update Posted:

Sep 29, 2017

Last Verified:

Sep 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by GlaxoSmithKline

Asthma

Additional relevant MeSH terms:

Pulmonary Disease, Chronic Obstructive

Salmeterol Xinafoate

Study Results

No Results Posted as of Sep 29, 2017