CompletedNCT01449799Updated Jul 28, 2017

An Investigation of the Pharmacokinetics of GSK961081 and Fluticasone Propionate in Healthy Volunteers

A Phase 1 interventional study of GSK961081 800 microgram dose and Fluticasone Propionate 500 microgram dose in Pulmonary Disease, Chronic Obstructive, sponsored by GlaxoSmithKline. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-07-28.

Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 24
Allocation: Randomized
Ages: 18 Years to 50 Years
Sex: All

Study summary

In the current study GSK961081 and fluticasone propionate will be administered in a blended formulation from a single device and compared with GSK961081 and fluticasone propionate administered alone and concurrently. This is a single centre, randomized, double-blind, double dummy, single dose, four way cross-over study investigating the pharmacokinetics and pharmacodynamics of GSK961081 and fluticasone propionate when administered alone, concurrently and as a combination blend in healthy subjects.

Read the detailed description

This will be the first time that GSK961081 and fluticasone propionate will be administered as a blend in humans. In previous clinical studies conducted in Chronic Obstructive Pulmonary Disease (COPD) patients, GSK961081 has been administered on a background of fluticasone propionate without any observed systemic pharmacodynamic interaction. In this study GSK961081 and fluticasone propionate will be administered in a blended formulation from a single device and compared with GSK961081 and fluticasone propionate administered alone and concurrently. The aim of the study will be to investigate any differences in pharmacodynamics and/or pharmacokinetics for GSK961081 and fluticasone propionate when administered as the blend, concurrently or alone.

Pharmacokinetic, pharmacodynamic and safety information will be gathered to assess the suitability of the GSK9610981/fluticasone propionate blend for further development.Each subject will receive four treatments (GSK961081 alone, fluticasone propionate alone, GSK961081 and fluticasone propionate concurrently, and GSK961081/fluticasone propionate blend) in randomized order, in four treatment periods, each separated by a washout period of at least a week. All treatments will be administered via a DISKUS inhaler.

Pharmacokinetics, pharmacodynamics and safety will be assessed by measurement of plasma GSK961081, plasma fluticasone propionate, serum cortisol, urine cortisol, blood glucose, serum potassium, Forced Expiratory Volume in one second (FEV1), heart rate, 12-lead Electrocardiograms (ECGs), clinical laboratory tests and collection of adverse events (AEs).

Conditions studied

Pulmonary Disease, Chronic Obstructive

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In context

Pulmonary Disease, Chronic Obstructive

4,131 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 697 are open to participants now.

This study's enrollment of 24 is below the median of 70 across 2,926 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.

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Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 50 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Male or female between 18 and 50 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the Investigator based on a medical evaluation including medical history, physical examination, laboratory tests and lung function testing. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures and outcome.
A female subject of child bearing potential, is eligible if she agrees to use one of the contraception methods listed in Section 8.1 of the protocol for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception for 5 half-lives after the end of the study (i.e. until after the follow-up visit is complete).
Body Mass Index (BMI) within the range 19.0 - 29.9 kilogram per square meter (kg/m2) (inclusive).
Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase and bilirubin less than 1.5 times the upper limit of normal (\<1.5xULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is less than 35%).
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Forced Expiratory Volume in 1 second (FEV1) greater than or equal to 80% predicted and a FEV1/ Forced Vital Capacity (FVC) ratio greater than or equal to 0.7.
Subjects who 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 less than or equal to 10 pack years.

[number of pack years = (number of cigarettes per day/20) x number of years smoked]

Exclusion criteria

Exclusion Criteria:

Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or electrocardiogram (ECG, 12-lead)
History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units for males or greater than 14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (around 240 millilitres, ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
QTc value corrected for Bassett or Fredericia [QTc(B) and QTc(F)] at screening greater than 450 milliseconds on an individual ECG, the 3 screening ECGs are not within 10% of the mean QTC value, a PR interval outside the range 120-210 msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave).
A supine blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg) at screening.
A supine mean heart rate outside the range 40-90 beats per minute (bpm) at screening.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
Where participation in the study would result in donation of blood or blood products in excess of 500 ml within a 90 day period.
Pregnant females as determined by positive serum Human Chorionic Gonadotrophin (hCG test) at screening or prior to dosing.
Lactating females.
Unwillingness or inability to follow the procedures outlined in the protocol.
Subject is mentally or legally incapacitated.
A history of respiratory disease (i.e. history of asthmatic symptoms) in the last 10 years.
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
A positive test for human immunodeficiency virus (HIV) antibody.
Urinary Cotinine/ Breath carbon monoxide (CO) levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
Night shift workers

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 24 participants (actual)

Study arms

Experimental
Sequence 1
In period 1, subjects will be administered GSK961081/fluticasone propionate blend via Diskus inhaler followed by the administration of GSK961081 and fluticasone propionate concurrently via separate Diskus inhalers in period 2. In period 3 and period 4, the subjects will receive fluticasone propionate and GSK961081 respectively.
Drug: GSK961081 800 microgram dose · Drug: Fluticasone Propionate 500 microgram dose · Drug: GSK961081 800 microgram and Fluticasone Propionate 500 microgram separately · Drug: GSK961081 800 microgram Fluticasone Propionate 500 microgram in a blend
Experimental
Sequence 2
In period 1, subjects will be administered GSK961081 and fluticasone propionate concurrently via separate Diskus inhalers followed by administration of GSK961081 in period 2. In period 3 and period 4, the subjects will receive GSK961081/fluticasone propionate blend via Diskus inhaler followed by the administration of fluticasone propionate respectively.
Drug: GSK961081 800 microgram dose · Drug: Fluticasone Propionate 500 microgram dose · Drug: GSK961081 800 microgram and Fluticasone Propionate 500 microgram separately · Drug: GSK961081 800 microgram Fluticasone Propionate 500 microgram in a blend
Experimental
Sequence 3
In period 1, subjects will be administered GSK961081 followed by administration of fluticasone propionate in period 2. In period 3, subjects will be administered GSK961081 and fluticasone propionate concurrently via separate Diskus inhalers followed by GSK961081/fluticasone propionate blend via Diskus inhaler in period 4.
Drug: GSK961081 800 microgram dose · Drug: Fluticasone Propionate 500 microgram dose · Drug: GSK961081 800 microgram and Fluticasone Propionate 500 microgram separately · Drug: GSK961081 800 microgram Fluticasone Propionate 500 microgram in a blend
Experimental
Sequence 4
In period 1, subjects will be administered fluticasone propionate followed by the administration of GSK961081/fluticasone propionate blend via Diskus inhaler in period 2. The subjects will receive GSK961081 in period 3 and concurrent administration of GSK961081 and fluticasone propionate in period 4.
Drug: GSK961081 800 microgram dose · Drug: Fluticasone Propionate 500 microgram dose · Drug: GSK961081 800 microgram and Fluticasone Propionate 500 microgram separately · Drug: GSK961081 800 microgram Fluticasone Propionate 500 microgram in a blend

Interventions

DrugGSK961081 800 microgram dose
To be provided via a combination of 4 inhalers - one 400 micrograms GSK961081 Diskus inhalation, a second 400 microgram GSK961081 Diskus inhalation and one inhalation each from two separate placebo Diskus inhalers
DrugFluticasone Propionate 500 microgram dose
To be provided via a combination of 4 inhalers - one 250 microgram fluticasone propionate Diskus inhalation, a second 250 microgram fluticasone proopionate Diskus inhalation, and one inhalation each from two separate placebo Diskus inhalers
DrugGSK961081 800 microgram and Fluticasone Propionate 500 microgram separately
To be provided via a combination of 4 inhalers - one 400 microgram GSK961081 Diskus inhalation, a second 400 microgram GSK961081 Diskus inhalation, one 250 microgram fluticasone propionate Diskus inhalation, and a second fluticasone propionate 250 microgram Diskus inhalation
DrugGSK961081 800 microgram Fluticasone Propionate 500 microgram in a blend
To be provided via a combination of 4 inhalers - one inhalation of a Diskus inhaler containing a blend of 400 microgram of GSK961081 and 250 microgram of fluticasone propionate per inhalation, a second inhalation of a Diskus inhaler containing a blend of 400 microgram of GSK961081 and 250 microgram of fluticasone propionate per inhalation, and one inhalation each from two separate placebo inhalers

What researchers measure

Primary outcomes

Plamsa concentrations and derived pharmacokinetic parameters of GSK961081 and fluticasone propionate
Maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve, and apparent terminal phase half-life (t1/2)\] for GSK961081 and fluticasone propionate
Time frame: From dosing to 24 hours post-dose

Secondary outcomes

Serum Cortisol
Concentration of the hormone cortisol in serum
Time frame: From dosing to 24 hours post-dose
Urinary Cortisol
Concentration of the hormone cortisol in urine
Time frame: From dosing to 24 hours post-dose
Heart Rate Changes
The maximum change and weighted mean change in heart rate from baseline (pre-dose)
Time frame: From dosing to 4 hours post-dose

Study locations

1 site

GSK Investigational Site
London, NW10 7EW, United Kingdom

References and documents

Publications

Norris V, Ambery C, Riley T. Pharmacokinetics and pharmacodynamics of GSK961081, a novel inhaled muscarinic antagonist beta2 -agonist, and fluticasone propionate administered alone, concurrently and as a combination blend formulation in healthy volunteers. Clin Pharmacol Drug Dev. 2014 Jul;3(4):305-13. doi: 10.1002/cpdd.105. Epub 2014 Feb 20. PubMed 27128837 ↗

Individual participant data

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

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 28, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01449799
Lead sponsor: GlaxoSmithKline
Responsible party: Sponsor
First posted: Oct 10, 2011
Start date: Jul 13, 2011
Primary completion: Sep 21, 2011
Completion: Sep 21, 2011
Last update: Jul 28, 2017

Study contacts

GSK Clinical Trials

study director · GlaxoSmithKline

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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