GSK159802 In Healthy Male Subjects And Asthmatics

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: GSK159802; Drug: Placebo; Drug: Salmeterol

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • GSK Investigational Site
  • Lancashire
    • Manchester, Lancashire, United Kingdom, M23 9LT
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment

Number of Arms

14

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety & tolerability of single inhaled doses of GSK159802.	Up to 71 days

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2005
• Primary Completion (Actual): July 6, 2006
• Study Completion (Actual): July 6, 2006

Study Registration Dates

• First Submitted: August 11, 2006
• First Submitted That Met QC Criteria: August 11, 2006
• First Posted (Estimate): August 15, 2006

Study Record Updates

• Last Update Posted (Actual): September 29, 2017
• Last Update Submitted That Met QC Criteria: September 27, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Salmeterol Xinafoate
• Other Study ID Numbers: B2F104300

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: B2F104300
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: B2F104300
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: B2F104300
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: B2F104300
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: B2F104300
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: B2F104300
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: B2F104300
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register